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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
KAREN J. BERKLEY
McKenzie Distinguished Professor of Neuroscience
Florida State University, Program in Neuroscience Tallahassee, FL USA
abstract
THE CHALLENGE OF PAIN IN THE XXI CENTURY
We are on the verge of major advances in our understanding of the neural
mechanism of pain. These advances derive from our growing recognition of
the importance of individual differences and the contribution of sociocultural
factors together with results of brain imaging studies and both PNS and CNS
neurochemistry and physiology. With these advances have come major
improvements in our understanding of how to diagnose and treat painful
conditions, by assessing each individual from using more patient-centered
approach and making better use of polytherapeutic strategies. These advances
are however limited to a select few. Thus, the real challenge in this new
century lies not only in recognizing and continuing these advances, but
perhaps more importantly in assuring application of them to individuals
throughout the world.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
MARIANO GIACCHI
Dipartimento di Fisiopatologia, Medicina Sperimentale e Sanità
Pubblica, University of Siena, Italy
abstract
HOSPITAL PROMOTING HEALTH (HPH) AND PAIN
MANAGEMENT
M. Giacchi, L. Canavacci
The principal aim of the health promotion strategy is to enable individuals
and communities
The aim of the Health Promotion as “process to enable individuals and
communities to increase control over the determinants of health and thereby
improve their health”.
Starting from the Budapest Declaration, the WHO Project Hospitals for
Health Promotion (HPH) has individuated a new and positive role the
hospital can assume in the perspective of the health promotion; the hospital
could be a privileged setting for an active intervention with programs and
objectives that overcome those traditional linked to the disease’s cure. The
specific project “Hospital without pain” proposes to contrast the pain e the
avoidable suffering, caused to the people by the diseases and the diagnostic
e therapeutic procedures, through a radical change of the attitudes and the
medical practice. Such change must involve not only the health workers but
also all citizens, so that they could manage more consciously own state of
disease. To reach the objective it is necessary to intervene at different
levels: training programs and sensitization of the health workers,
information and empowerment of the patients, setting-up methods for
measuring and registering different levels of pain, adoption of effective
clinic protocols, organizative adjustment, multi-disciplinary approach and
working group in treating the patient with pain.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
JOHN LEE
UCL Hospitals, National Hospital for Neurology and Neurosurgery
London, UK
abstract
PAIN IN THE POPULATION
The prevalence of long term pain in the UK is somewhere between 20 and
50%; this is consistent with international studies suggesting that different
societies have major chronic pain problems. However, the evolution of
pain comes from many factors. Tissues damage often precipitates it, but it
can be given credence by physicians and society which promote a state of
ill health. Many of the determinants of chronic pain are similar to those for
other major health problems e.g. low social class, limited education,
employment status, psychological distress, depression and smoking. The
management of patients with long term pain require an understanding of the
role of sickness in society, and all the different factors which affect any
individual. A wider understanding of pain and its determinants will assist
politicians, health policy advisers, Public Health and general physicians to
resource and support this pervasive problem more appropriately.
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3
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
ANNA WEISS
Royal Cornwall Hospital Truro, Cornwall UK
abstract
EDUCATION AND PAIN
Pain is the main presenting symptom that invites patients to seek medical
help. There is a clear disparity between the ubiquity of this symptom and
the amount of time and effort spent on teaching Pain Medicine, either in
medical schools or within postgraduate medical training. The art of pain
relief is sometimes being seen as ‘masking symptoms’ and as a patient’s’
need, that is secondary to the need for a definite diagnosis or so called
curative treatments.
Is this rather bleak view of pain medicine reflected in present Pain
Medicine Undergraduate teaching?
How does education in Pain Medicine vary across the UK? Can any
common features of Pain Medicine training be found internationally?
The presentation will address these questions and hopefully encourage a
lively exchange of views within the auditorium. Data of a survey performed
across the UK will form the basis of this contribution
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
CATHERINE PRICE
Southampton University Hospital, Southampton, UK
abstract
PAIN IN THE WORKPLACE
The majority of patients attending pain clinics report pain relief as a result
of treatment yet very few report absolute pain relief. (3% of all attending
UK pain clinics). 70% of patients present with pain as their primary
symptom to a hospital. 40% of the population suffer from continuous pain,
yet very few require specialist services, the vast majority are managed by
primary care services such as general practitioners, community pharmacists
and physiotherapists, albeit in an incoherent fashion. Mental Health
services also see those who a have developed severe anxiety and depression
due to chronic pain. There is no framework in which to operate in the UK at
present. This causes specialist pain services enormous difficulty in defining
to others who would benefit from their services. The vast majority of pain
services struggle to keep maintain a reasonable waiting time. There a
potential referral base of at least 70000 patients in Southampton, yet
capacity to treat 520! We therefore reworked our service to this model of
care.
A chronic disease management approach was deemed the most likely
successful service model. A stepped care approach as described by Von
Korff was taken. A screening team and operational policy were drawn up
with all stakeholders involved. For nearly half of patients referred specialist
pain services are not appropriate. Guidelines in themselves have had a
relatively weak effect on referral behaviour. The vast majority of patients
are not ready for self management in the first instance. Depression is one of
the major limiting factors to engaging in self management. We conclude
that a pain assessment service operating within a closely defined framework
can markedly reduce the pressure on specialist pain services.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
MARY NEWTON
University College London Hospitals, The National Hospital for Neurology
and Neurosurgery, Queen Square, London, (UK)
abstract
ACUTE
PAIN
MANAGEMENT
NEUROSURGICAL PATIENT
OF
THE
The acute pain team at The National Hospital for Neurology and
Neurosurgery (NHNN) was formed in 1997 following national
recommendations. The acute pain team holds a daily ward round but is
available for advice or visits to patients at all times.
The main aims of the team have been to improve the pain management of
patients in this hospital by a continuing process of education of nursing and
medical personnel, combined with an active program of audit and research.
The incidence of severe pain in the post-operative phase has been reduced
from 40% in 1999 to 7% in 2002. We feel that this fantastic improvement
in post-operative pain is largely attributable to the introduction of NHNN
acute pain management guidelines, the demonstration that morphine can be
used safely in this group of patients and a large increase in the regular
administration of co-analgesics.
We still have a problem with severe post-operative pain in the immediate
post-operative phase in many of our patients. This is mainly because many
of the analgesics available to us are contraindicated in this group of
patients. We hope to introduce COX-2 inhibitors intra-operatively and
reassess their effect on immediate post-operative pain with a repeat audit.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
ANNA MANDEVILLE
Pain Management Centre, University College London Hospitals, London, UK
abstract
COGNITIVE-BEHAVIOURAL TREATMENT FOR PAIN
Cognitive and behavioural-based treatments for the management of chronic
pain, including group pain management programmes, have proliferated on a
world-wide scale and an extensive international literature now exists
demonstrating the efficacy of these approaches. This presentation aims to
give an outline of cognitive-behavioural-based approaches that involve both
specialist psychologists and specialist physiotherapists. These approaches
aim to help people with chronic pain to become fitter and to systematically
resume activities they had previously avoided because of pain. They are
taught to identify and challenge unhelpful ways of thinking about their pain
and, through information, education and experimentation, to overcome
fears they may have about causing potential harm to themselves by
increasing their activity levels. These approaches aim to help people limit
their chronic pain whilst improving their activity levels and their mood and
often whilst reducing their use of analgesic medication, where this is no
longer having any beneficial effect.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
SARAH FERGUSON
Pain Clinic, Royal United Hospital, Combe Park, Bath (UK)
abstract
MANAGEMENT OF BACK PAIN IN PRIMARY CARE
Low Back Pain (LBP) is a major health problem reaching epidemic
proportions. It is usually self limiting and benign and tends to improve over
time. There is compelling evidence that physical activity is important for
health with prolonged inactivity leading to reduction in joint motion,
muscle strength and a marked decline in physical fitness. There is a
pressing need for Back Pain services to be away from a hospital or medical
setting.
In an attempt to “demedicalise” LBP, two new and innovative programmes
are currently running in leisure centres. The first is the Healthy Back Class
(HBC), this is a general exercise class for LBP sufferers taken by fitness
instructors. Seventy percent of the clients are returning to normal activities
and self refer to the classes. Satisfaction surveys showed clients improved
posture, flexibility, self-confidence, and quality of life and “learnt about
their backs”. Results show that they are more able to cope with their back
pain without consulting with their general practitioner.
The second, is the Back Rehabilitation Programme (BRP). This is a specific
four week programme based on the normal model of behaviour (rather than
disease model) and cognitive behavioural principles. This approach is
widely accepted as important for those who are not recovering from their
episode of LBP at about four to six weeks. Reactivation programmes in
general have been shown to reduce work loss and related costs, improve
function, reduce pain, return to normal activity quicker, improve clinical
status and reduce disability. Results will be presented at the conference.
The UK National Back pain Collaborative (NHS Modernisation Agency)
has endorsed both programmes.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
FRANCESCO MAROTTA
Surgery Department, Rome University Tor Vergata, Pain Service, Rome
abstract
“UNTREATABLE”
PAIN
IN
CANCER
INNOVATIVE, PORTABLE BIOPHYSICS
MIMICKING ARTIFICIAL NEURONS.
Marineo G., Spaziani S., Sabato A. F., Marotta F.
PATIENT:
AN
METHODOLOGY
Introduction. We had previously presented a novel bioengineer
methodology (Scrambler Therapy, ST5) to treat severe oncological pain
resistant to medical treatment. We report about an improved device in a
larger controlled study. The natural course of the any malignant disease will
invariably worsen the pain while involving more complex perception such
as “viscero-somatic” and/or “viscero-neurogenic” pain. Methods &
Results. In this study we selected cancer patients to study the performance
of ST5 methodology which is able to deceive the “pain signal” into a “nopain” message by means of artificial neurons activity. This is accomplished
by a construction of a set of wave forms (basic coding) which, when
assembled in real time by suitable control algorithms, can simulate the
geometric trend specific to endogenous (“self”) biopotentials thus achieving
a very quick anaelgesia (within seconds). Moreover, such dynamic
generation using artificial neurons of "packets" (strings) of information
recognized as "non pain" is algorithmically-driven as to reduce the
adaptation of the perception as a function of the noise. The related
amplitude is such that it may be decoded as the dominant stimulus by
means of the over-modulation of the endogenous biopotentials. Drugs were
eliminated in a stepwise fashion during the trial perioddepending on the
response to the daily sessions of scrambler therapy. Conclusion. This
further enables to totally halt the pharmacological pain-killer therapy(70%)
or yield an 80% reduction of it (30%). With the present improved
ST5methodology, visceral pain is shown to be very successfully treated
also in elderly cancer patients being suitable to home-treatment with a
substantial QOL impact on the patient and family environment.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
TRUDY TOWELL
Queens Medical Centre, Nottingham- UK
abstract
NURSE-LED ACUPUNCTURE IN THE PAIN CLINIC
The Department of Health (1999) reports that acupuncture is used by 86%
of chronic pain services. Our patients are referred for acupuncture by the
consultants and initially they receive a four week course of weekly
treatments. The patients are asked to complete an adapted version of the
Brief Pain Inventory, before and after the acupuncture course. The
inventory outcomes include the effect on sleep, well-being, quality of life,
function, pain intensity and perception of pain relief. The patient and nurse
assess the response which, if deemed successful, leads to regular top-up
treatments as determined by the waiting list.
This paper will present the results of one pain clinics nurse-led
acupuncture. Many of the patients referred, request on-going top-up
treatments which suggest they may view acupuncture as beneficial for
chronic pain management.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
GIUSEPPE DE BENEDITTIS
Pain Research & Treatment Unit, Department of Neurological
Sciences, University of Milan, Italy.
abstract
HYPNOSIS AS A PHYSIOLOGICALLY EFFECTIVE TOOL FOR CONTROLLING
PAIN AND EXPLORING THE CENTRAL NERVOUS SYSTEM: A COPERNICAN
REVOLUTION ?
An increasing body of evidence has shown that hypnosis can be effective in the downmodulation of the pain sensation in both acute and chronic pain states. In acute pain, the effect
of hypnotic analgesia is specific, positively correlated with hypnotic responsiveness and
unrelated to endogenous opioid mechanisms.
The neural mechanisms underlying hypnotic states and responses to hypnotic suggestions of
analgesia remain largely unknown.
Recent evidence has shed, at least, some light on the mistery of pain relief in hypnosis. It is
likely that hypnotic suggestions of analgesia may modulate pain processing at multiple levels
and sites within the peripheral and central nervous system. At peripheral level, hypnosis may
modulate nociceptive input by down-regulating A-delta and C fibres stimulation and reducing
sympathetic arousal. At spinal level, sensory analgesia during hypnosis has been shown to be
linearly related to a reduction of the nociceptive flexion (RIII) reflex, a polysynaptic spinal
reflex.
At supraspinal level, neuroimaging and electrophysiological studies have shown that hypnotic
suggestions of analgesia can modulate both sensory and affective dimensions of the pain
perception (the affective being reduced more than the sensory), thus confirming, at least
partially, the neo-dissociation theory by Hilgard &Hilgard (1994). Moreover, highly
hypnotizable subjects possess stronger attentional filtering abilities than do low hypnotizable
subjects. This greater cognitive flexibility might result in better focusing and diverting
attention from the nociceptive stimulus as well as better ignoring irrelevant stimuli in the
environment. Cognitive control processes are associated with a “supervisory attentional
system”, involving the far frontal limbic cortex.Multiple, hierarchical pain control systems
during hypnotic suggestions of analgesia provide a new description of the neurobiological
basis of hypnotic analgesia, which has beeen established as a viable, valid and reliable
intervention for controlling acute and chronic pain.
Furthermore, recent research paradigms have eventually fostered hypnosis as a
physiologically effective probe into brain mechanisms and, reciprocally, provide a means of
studying hypnosis . This seems really to be the beginning of a Copernican revolution in the
field.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
JONATHAN FRANCIS
Cheltenham General Hospital, Gloucestershire, (UK)
abstract
UK GUIDELINES ON OPIOID THERAPY
Chronic non-cancer pain is common. Simple analgesics have limited
effectiveness often leaving patients and their doctors frustrated. Strong
opioids are our most powerful analgesics, but prejudice, ignorance and fear
of addiction remain barriers to their use in the treatment of chronic noncancer pain.
The Pain Society of the UK has produced guidance to doctors and patients
who may consider the use of strong opioid treatment. Careful patient
selection and consent along with good communication between specialists
and family doctors is essential to deliver safe and effective analgesia.
Whilst side effects are common they are seldom serious and easily treated.
Problem behaviours such as addiction are rare but potentially disastrous:
regular assessment and a good understanding of tolerance, dependence and
addiction enables early identification and treatment.
A good knowledge of drug pharmacology allows a rational approach to
strong opiate use; practical considerations and approaches will be
considered.
Strong opioids may be an option for the large number of patients with
inadequately treated non-caner pain. This talk highlights the important
issues and reflects the guidance given to doctors and patients in the UK.
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12
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
JON VALENTINE
Norfolk and Norwich University Hospital, Norwich, UK.
abstract
INTRATECAL DRUG DELIVERY
Many pain management physicians believe intrathecal drug delivery can
play an important role in the management of both chronic benign and
malignant pain. Unfortunately, the provision of an intrathecal drug delivery
services varies greatly between UK centres for reasons including
experience in the technique, patient referral, health service funding and the
absence of a strong evidence base. There are several systems that can be
used for the delivery intrathecal drugs ranging from inexpensive, simple
percutaneous catheters through to costly, high tech, implanted, multiprogrammable infusion pumps. Morphine remains the most commonly
infused intrathecal analgesic although other opiates and adjuvant analgesics
such as bupivicaine and clonidine may be added. Whilst benefits in terms
of pain relief can be high, complications are not uncommon and can range
from the inconvenient to the life threatening. A full multidisciplinary team
approach is required to assess, prepare and care for these patients who often
have very complex pain management problems.
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13
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
ANDREW BARANOWSKI
National Hospital for Neurology and Neurosurgery, London (UK)
abstract
UROGENITAL PAIN, AN OVERVIEW
An understanding of the mechanisms of chronic pain has only been realised
over the past 40 years or so. The mechanisms associated with chronic
neuropathic and musculoskeletal pain over lap with those of urogenital pain
with a few exceptions specific to the viscus. When a patient presents with
urogenital pain it is important to assess beyond the primary area of
perceived pain and to consider mechanisms such as neuropathic and
musculoskeletal. The processes of central sensitisation and muscle
hyperalgesia are as relevant to chronic visceral pain as to any other
condition. Treatments aimed at these areas may produce significant benefit.
Psychological distress may be secondary to the pain problem and it should
not be assumed that in a patient with psychological issues that the pain is
secondary to those issues.
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14
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
SIAN I. JAGGAR
Royal Brompton Hospital, London, UK.
abstract
INDRODUCTION TO ANIMAL MODELS OF VISCERAL PAIN
Much information regarding the pathophysiology of pain mechanisms has
been derived from the use of animal models. It is important to understand
the basis upon which deductions are made, since this will have an important
influence upon the relevance of such material.
An ideal animal model of pain must demonstrate both ideal features of
stimulus and response. The stimulus should be:
 Representative of the clinical condition it aims to model.
 Minimally invasive (to avoid stimulating areas not under
investigation).
 Controllable.
 Reproducible.
 Quantifiable.
The response characteristics should be:
 Observable in an awake animal (the most ‘obvious’ pain response
being removal of the area from pain).
 Reliable.
 Reproducible.
 Quantifiable.
 Representative of clinical conditions.
Such features are difficult to achieve for the viscera, since the organs are
internal, so why is it worth it?
1. Visceral pain is very common - the clinical impact will be great.
2. Visceral pain differs from that arising in somatic tissues appropriate management strategies are likely to differ.
These features should all be considered when assessing the relevance of an
article to your clinical practice.
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15
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
CARLO LUCA ROMANO’
Istituto G. Pini - Department of Orthopaedics - Milano - Italy
abstract
MULTIPLE PINS PRESSURE REDUCES PIN-PRICK PAIN OF
INTRA-MUSCULAR AND SUBCUTANEOUS INJECTIONS.
Romanò C. L., Cecca E., Cirigliano C., Marchese D., Romanò D.
Background: While about ten percent of the normal population is thought
to be needle-phobic, no method to reduce pin-prick pain is currently available
for large scale application.
Purpose of the study: to evaluate the efficacy and safety of a new method to
reduce pin-prick pain through the pressure of multiple pins at the injection
site. 212 patients were randomly assigned to two groups.
In the first group injections were performed with a placebo device (an
oval plastic disk pressed onto the skin, without pins). In the second group,
injections were performed with a plastic device, that consists of an oval disk
that supports multiple blunt pins. In the middle of the oval support is a hole
through which the injection needle in inserted during the injection procedure.
Results: Pin-prick pain was rated by the patients according to a Visual
Analogue Score (V.A.S.): 0 (no pain) - 10 (maximum pain). After intramuscular injections 13.1 % of the patients in the placebo and 90.1
% in the treated group rated the pain as < 3. Mean +- S.D. V.A.S was 5.16 +1.37 in the placebo and 1.90 +- 1.27 in the treated group (p<0.0001) (mean
pain reduction: 63.2 %).
After subcutaneous injections 10.1 % of the patients in the placebo and
97.5 % in the treated group rated the pain as < 1. Mean +- S.D. V.A.S.
was 2.61 +- 0.77 in the placebo and 0.32 +- 0.51 in the treated group (p
< 0.0001) (mean pain reduction: 87.7 %).
6 patients (5.6 %) in the treated group showed a transient local inflammation
that spontaneously resolved after few minutes, withouttreatment.
Conclusion: The pressure of multiple pins at the injection site
significantly reduces the pain connected with pin-prick of intra-muscular or
subcutaneous injections. The underlying physiological
mechanisms are discussed.
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16
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
LESLEY BROMLEY
University College London, UK
abstract
ACUTE PAIN - PATHOPHYSIOLOGY
The understanding of the physiological processes involved in acute
nociception has increased greatly over the preceding 10 years. Our view of
the nervous system as a plastic system which responds to incoming stimuli
in a spatial and temporal manner has allowed us to understand acute pain in
a more scientific way.
These responses occur at every level of transmission, from the peripheral
site of injury, through the spinal cord to the brain stem, and cortex.
The current knowledge of the process will be reviewed in this talk, with
particular reference to the new understanding of the role of the glial cells in
the central nervous system, and the role of central cyclooxygenase in
modulating pain perception.
A model of the body neuromatrix as a representation of pain perception will
be introduced.
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17
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
LAURA PERISSIN
School of Medicine, University of Udine, Udine, Italy.
abstract
CHRONOBIOLIOGICAL ASPECTS OF PAIN
The chronobiology of pain and analgesia is an interesting issue, both on
theoretical and therapeutic grounds. There is evidence for diurnal,
infradian and seasonal variations in pain sensations and reactions, in the
effects of analgesic drugs, and in pain symptoms associated with many
disorders. However, there appears to be no general consensus on the
presence and characteristics not only of circadian but also of seasonal
rhythms in the responses to noxious stimulation, even in the same species.
In this connection, the choice of specific experimental pain models which
permits to evaluate and, particularly, to distinguish between the
chronobiological variations of pain tolerance and pain threshold, appears
crucial. Data obtained in the author lab employing the formalin test as
experimental model of injury-induced (tonic) pain, indicate that significant
seasonal and diurnal variations exist of nociceptive responses in mice. The
analgesic effects of morphine are also affected in a similar way. The
mechanisms involved in chronobiological changes of nociception seem to
be controlled by the endogenous 'zeitgeber' pineal gland and its hormone
melatonin that probably modulate endogenous opioid level and/or opiate
receptors.
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18
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
CARLO VALERIO BELLIENI
Department of Pediatrics, Obstetrics and Reproduction
Medicine, University of Siena, Italy
abstract
SENSORAL SATURATION IS ANALGESIC IN TERM
NEWBORNS: A RANDOMIZED CONTROLLED TRIAL
Carlo Valerio Bellieni, Franco Bagnoli, Diccio Maria Cordelli, Giuseppe
Buonocore
Many attempts have been made to obtain safe and effective analgesia in
newborns. Oral sugar has been found to have real analgesic power. We
investigated whether other sensory stimulation added to oral glucose
provided more effective analgesia than oral glucose alone. In a randomised
prospective double-blind trial we studied 120 term newborns during heel
prick. The babies were divided randomly into six groups of 20 and each
group was treated with a different procedure during heel prick: A) control;
B) 1 ml 33% oral glucose; C) sucking; D) 1 ml 33% oral glucose + sucking;
E) multisensory stimulation including 1 ml 33% oral glucose (sensorial
saturation); F) multisensory stimulation without oral glucose. Sensorial
saturation consisted in massage, voice, eye contact and perfume smelling
during heel prick. Each heel prick was filmed and assigned a point score
according to the DAN neonatal acute pain scale. Procedure E was found to
be the most effective (p<0.0001) and its analgesia was more effective even
when compared with procedure D (p=0.0028). We conclude that sensorial
saturation is an effective analgesic technique that potentiates the analgesic
effect of oral sugar. It can be used for minor painful procedures on
newborns.
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19
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
GIANCARLO CARLI
Department of Physiology, University of Siena, Italy
WELL-BEING IN PATIENTS WITH FIBROMYALGIA AND DIFFUSE
MUSCULOSKELETAL PAIN
Giancarlo Carli and Anna Lisa Suman, University of Siena, Italy
OBJECTIVES: several previous studies have underlined that fybromyalgia [FMS]
is frequently associated with mood disorders. The aim of our research was to
determine whether, in the same patients, it is possible the occurrence of both
chronic pain and well-being .
METHODS One-hundred and thirty-two women with diffuse musculoskeletal
pain, 56 of whom met the American College of Rheumatology[ACR]
classification criteria for FMS, were submitted to Multidimensional Affect and
Pain Survey [MAPS], a questionnaire with 101 descriptors and negative and
positive emotions, containing 30 clusters subsumed within 3 superclusters
[Somatosensory Pain, Emotional Pain, Well-Being, expressed on a 0-5 scale].
Patients were submitted also to Symptom Check List [SCL-90], STAI Y1 and
STAI Y2 and to a Face Scale.
RESULTS On the whole population,Well-being had a higher score [2.8] than
Somatosensory Pain [2.3] and Emotional Pain In particular, about 30% of the
patients displayed a relatively good level of Well-Being [3.5].There were no
differences between FS and the other patients.
Moreover Well-being was negatively correlated with SCL-90 depression [Pearson
correlation coefficient: r= -.422; p < .01] and STAI Y2 [r = - .414; p < .01]. The
Face Scale confirmed good scores in mood level in about 30% of the patients.
CONCLUSIONS: Results indicate that good levels in mood can occur in patients
suffering for chronic musculoskeletal pain independently from the severity of
clinical parameters
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
ROBERTO CASALE
Fondazione S. Maugeri, Clinica del Lavoro e della Riabilitazione,
Montescano (PV), Italy
abstract
THE USE OF BOTULINE TOXIN IN THE MANAGEMENT
OF PAIN
Acetylcholine (Ach) is the main neurotransmitter involved in striated
muscle contractions as well as in the autonomic nervous system (ANS). In
the skeletal muscles it binds to nicotinic receptors on the post-synaptic
membrane. In the ANS it binds to the nicotinic receptors present in the preganglionic synapses of the sympathetic nervous system and both the preand post-ganglionic synapses of the parasympathetic nervous system.
The successful pain control that can be achieved with BT is, therefore,
linked to its ability to block the Ach from all the cholinergic nerve
terminals in both the musculoskeletal and the autonomic nervous systems.
BT seems also to posses a pure anti-nociceptive action exerted through a
reduction of peripheral sensitisation: BT down regulates positive feedback,
inhibiting the release of pro-algesic neuropeptides. The reduction of
peripheral inputs to the spinal cord contributes to reducing central
sensitisation.
The use of type A botulin toxin in the management of pain is a recent field
of research. Although there are numerous researchers currently using this
toxin for a wide range of painful muscle syndromes, neither the American
FDA nor the Italian authorities currently recognize this indication.
Although extremely promising, its use must therefore be considered as an
“off-label” clinical application.
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ANITA HOLDCROFT
Chelsea and Westminster Hospital, Imperial College London , London, UK.
21
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
GENDER AFFECTS PAIN THERAPY
One of the challenging issues of pain management emerging from sciencerelated and clinical research is how to improve pain relief for an individual
patient. The evidence basis for sex and gender differences in pain and its
relief is rapidly increasing. The interactions between and individual
contributions of genetic, physiological, anatomical, neural, hormonal,
psychological, lifestyle and sociocultural factors make decisions on pain
relief based on sex and gender complicated and strongly related to age and
time of study. In addition there are significant differences in these
interactions between species such that metabolism of drugs can differ
between humans and rodents [1].
Through studies of patients in pain after surgery [2, 3] or in the community
[4], gender differences in opioid use have been measured. In some
postoperative studies males have been found to regularly use more opioids
than females whereas in the community females have a greater burden of
pain and seek its relief. The mechanisms for these findings include
psychological and biological differences and warrant further study.
However, their translation into health care is starting to develop through
pain curricula, specific drug development and gender based clinical trials.
[1] Holdcroft A, Berkley KJ. “Sex and Gender Differences in Pain and its
Relief” 5th Ed ‘Wall and Melzack Textbook of Pain’ Chapter 74, Eds S.
McMahon and M. Koltzenburg (Churchill Livingstone, Edinburgh) 2004
in press.
[2] Chia YY, Chow LH, Hung CC, Liu K, Ger LP, Wang PN. Can J
Anaesth 2002;49:249-55
[3] Cepeda MS, Carr DB. Anesth Analg 2003;97:1464-8.
[4] Isacson D, Bingefors K. Eur J Anaesthesiol Suppl 2002;26:5 – 15.
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CARLO A. PORRO
Dipartimento Scienze e Tecnologie Biomediche, Università di Udine,
22
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Udine, Italy
abstract
PAIN IMAGING IN HEALTH AND DISEASE
In healthy human volunteers, pain intensity-related hemodynamic changes
have been identified in a widespread, bilateral brain system including
parietal, insular, cingulate and frontal cortical areas, as well as thalamus,
amygdala and midbrain, during different kinds of acute noxious
stimulation. Some cortical areas, such as the perigenual cingulated cortex,
appear to be specifically related to the affective aspects of pain. Specific
patterns of nociceptive activity may characterize hyperalgesic states and
some, but not all, chronic pain conditions. Both animal and human imaging
studies suggest that forebrain nociceptive systems are under inhibitory
control by endogenous opioids; in humans, acute administration of -opioid
receptor agonists blunts noxious heat-evoked activation in several brain
areas. Anticipation of pain may in itself induce changes in brain nociceptive
networks. Moreover, pain-related increases in cortical activity can be
modulated by different cognitive processes, such as hypnotic suggestions,
focussing or diverting attention, and placebo. These findings highlight the
complexity of the pain system, and begin to disclose the spatio-temporal
dynamics of brain networks underlying pain perception and modulation in
health and disease.
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VITTORIO VELLANI
Department of Biomedical Sciences, University of Modena, Italy.
23
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
PERIPHERAL MECHANISMS OF SENSITISATION TO NOXIUS
STIMULI MEDIATED BY PKC
Vittorio Vellani, Pier Cosimo Magherini and Peter A. McNaughton.
Pain is initiated by the activation of specific pain-sensitive neurons, or
nociceptors, whose sensory terminals express a range of specific membrane
receptors responsible for detecting different noxious stimuli. Activation of
PKC by inflammatory mediators causes an increase in the sensitivity of the
nociceptor to a variety of noxious stimuli. We employed a sensory neurones
preparation in culture to show that many different g-protein coupled
receptors activated by inflammatory mediators produce sensitisation to
noxious stimuli via activation of one specific isoform of PKC – PKCepsilon – out of the five PKC isoforms expressed in dorsal root ganglia
(DRG) neurones (beta1 and beta2, delta, epsilon and zeta). Using PKCepsilon translocation to the membrane as an essay of receptor activation,
and combined Ca-imaging and electrophysiology, we show that specific
subpopulations of DRG neurones express specific patterns of g-protein
coupled receptors and ion channels involved in the generation, maintenance
and modulation of the pain signal. Our data supports the idea that isotypespecific antagonists designed to prevent or reduce PKC-epsilon activation
may have therapeutic potential as analgesics, likely to be capable of
reducing or suppressing inflammatory pain.
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THOMAS HERDEGEN
24
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Institute of Pharmacology, University of Kiel, Germany
abstract
INTRANEURONAL SIGNALLING INVOLVED IN
CHRONIC PAIN
Chronic pain is characterised by lasting alterations in signal
transduction including expression of genes and posttranslational
modifications. It is a provocative hypothesis that the cure of chronic
pain also demands the reversion of altered genetic programs and
signal transduction. It is known that the lasting upregulation of the
FosB/AP-1 transcription results in non-reversible alterations of
neuronal programs. Moreover, repetitive application of highly
intensive stimuli results in lasting habituation of MAP kinases.
This presentation will summarize and speculate on the pathological
alteration of signal transduction and gene expression underlying
chronic pain, and about the strategies to reverse these pathological
changes.
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GABRIELE ELISEO MARIO BIELLA
Institute of Molecular Bioimaging and Physiology, CNR Milan, Italy
25
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
SPINAL AND SUPRASPINAL PAIN INTEGRATIVE SYSTEMS
Maurizio Manuguerra*+, Marco Brambilla*, Stefano Panzeri°, Maria Luisa
Sotgiu*, Maurizio Valente* and Gabriele E.M Biella*
*Institute of Molecular Bioimaging and Physiology, National
Research Council, Milan; +ISI, Turin, Italy; °UMIST, University of Manchester,
UK
Pain (chronic pain, in special focus) is the final neuropsychological event of a
complex neurodynamic and neuropathological event cascade. The inner nature of
the cascade is all but clear and, additionally, no potential solution for the
neurodynamic-neuropsychological connection seems available so far.
Anyway, the psychological issue of pain is the front-end context of a neural
trade-off i.e pain is the product of neuronal dynamical interactions. Thus to try to
understand pain, some deeper insight in the neuronal activity profiles and
neuronal interactions in models of pain seem valuable.
In our experiments on different chronic pain models (neuropathic and
inflammatory models, involving monolateral hind limb manipulation) the activity
of simultaneously recorded thalamic and cortical neurons is studied. Experiments
are carried out on gas-anesthetized animals (Isoflurane and Oxygen). Multipleelectrode arrays are used to record from the somatosensory cortex and from the
ventrobasal nuclei of the thalamus, contralaterally to the injured paws.
The data are analyzed both for populations and for single units by information
theory means and by non linear methods, thus accounting for single dynamic
trajectories and for interaction dynamics.
Important, stable and significant difference shall be shown both for single unit
and population analyses and for information transfer rates between the models
and the normal animals.
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____________________________________________________________________________________
SANJAY KHANNA
26
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Neurophysiology Laboratory Department of Physiology
National University of Singapore, Singapore
abstract
HIPPOCAMPUS
AND
ELECTROPHISIOLOGICAL AND
EXPLORATION OF FIELD CA1
NOCICEPTION:
IMMUNOCYTOCHEMICAL
The hippocampal formation, which has long been associated with learning
and memory, may also provide a neural basis for aversive drive and affect
to pain. Indeed, manipulations of the hippocampus in animals with
electrical stimulation, microinjection of pharmacological agents or lesion
are reported to inhibit avoidance response to painful shock in conditioning
paradigms and attenuate indices of nociception to unconditioned peripheral
application of noxious stimulus. In humans, a recent functional imaging
study indicated that the hippocampal formation is activated during
mismatch from expectation of noxious stimulus but not non-noxious
stimulus. We have focused on investigating the neural and cellular
responses of neurons in field CA1 to noxious stimulation, including with
subcutaneous injection of formalin into a hind paw of rat, an animal model
of clinical inflammatory pain. The functional studies conducted in our
laboratory using a combination of electrophysiology and c-Fos expression
mapping have indicated that the characteristics of neural responses in field
CA1 are consistent with the notion that the region comprises part of the
‘medial pain system’. In this context, nociceptive information is processed
in a distributed fashion along the length of field CA1. Further, the pattern
of neural and cellular responses in field CA1 reflected nociceptive intensity
raising the possibility that CA1 acts as a ‘central intensity monitor’. The
neural changes were sensitive to systemic administration of morphine
which exercised its influence partly via an effect on septohippocampal
neural processing. Finally, the investigations also highlight the possibility
that a pathway from posterior hypothalamus may influence hippocampal
nociceptive response via a relay in medial septum.
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GIORGIO CRUCCU
27
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Dipartimento Scienze Neurologiche, Università La Sapienza, Roma
abstract
TRIGEMINAL PAIN MECHANISMS
The trigeminal system mediates all the oral, facial, and head pains, whether
neuropathic or nociceptive. Some of these pain syndromes are clinically
unique (e.g. trigeminal neuralgia and its trigger mechanisms, burning mouth
syndrome, or temporomandibular dysfunction) possibly because of the many
peculiarities of the anatomical-functional organisation of the trigeminal system.
In the trigeminal territory lie the corneal mucosa and dental pulps, which are
special organs exclusively innervated by free nerve endings, mostly
nociceptive. The oral mucosa and perioral skin have a very high density of
thermal and nociceptive unmyelinated afferents. Proprioceptors are
comparatively very few and exert a minimal role in modulating motoneuronal
activity. Trigeminal motoneurons are devoid of recurrent or reciprocal
inhibition; in contrast they undergo a powerful inhibition by perioral
mechanoreceptors. This organization, in particular the inhibition arising from
peri- and intraoral receptors, is thought to play a role in masticatory myofascial
pains. The trigeminal sensory root contains a huge number of afferents and its
connective membranes are particularly thin. This may partly explain why
chronic benign compressions can induce the demyelination-remyelination
phenomena responsible for the ectopic generation of impulses in trigeminal
neuralgia. Second-order-neurons (and primary proprioceptive neurons) lie in
separate nuclei dedicated to specific sensory modalities. The spinal trigeminal
complex, extending from the pons to the C2 spinal segment, has in its pars
caudalis the so-called medullary dorsal horn with its layers of nociceptive
specific and wide-dynamic-range neurons, which nonetheless differs from the
spinal dorsal horn. Similarly to the spinal system, the trigeminal system finally
projects to the somatosensory primary and secondary cortices (SI and SII) in
the parietal lobe and thermal-nociceptive inputs also reach the insula and the
anterior cingulated gyrus. In contrast with the classical description of the
sensory homunculus, whereas the input from the lower and upper facial
territories are largely overlapped in SI, the lower territories are represented
mostly contralaterally and the upper territories bilaterally in both SI and SII.
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GIANDOMENICO IANNETTI
28
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Department of Human Anatomy and Genetics and FMRIB Centre,
University of Oxford, UK
abstract
LASER STIMULATION IN PAIN RESEARCH
Powerful and brief laser stimulation of the skin produces a fast heating
restricted to the most superficial layers, where only the free-nerve endings
innervated by small-myelinated A-delta and unmyelinated C fibres lie.
Correspondingly, a painful, suprathreshold single laser radiant heat pulse
applied to the skin elicits the classical double sensation of first and second
pain, and A-delta related evoked potentials/magnetic fields can be recorded
from the scalp using EEG/MEG (late laser evoked responses, LERs). By
exploiting the different physiological properties of A-delta and C-fiber
nociceptors (resistance to ischemia, heat threshold, distribution density) it is
possible to activate selectively C-fibers without the coactivation of A-delta
fibres, producing the sensation of second pain only and eliciting C related
evoked potentials (ultralate LERs).
The cortical regions most consistently identified as sources of scalp LERs
are the operculoinsular and the anterior cingulate (ACC) cortex.
Participation of the primary somatosensory cortex (SI) to explain LER
scalp distribution remains controversial, but evidence is emerging that both
SI and opercular sources may be concomitantly activated by laser pulses,
with very similar time courses.
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FLAMINIA PAVONE
29
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Institute of Neuroscience, CNR, Psychobiology and Psychopharmacology,
Roma, Italy.
abstract
CLOSTRIDIAL NEUROTOXINS: NEW TOOLS FOR THE STUDY
OF THE PHARMACOLOGY OF PAIN
Neurotoxins affecting neuroexocytosis can represent an innovative
pharmacological approach to the investigation of neural mechanisms of
pain. In particular, our interest has been focused on the use of Botulinum
toxins, which are going to have a longterm place value in pain therapy, too.
Strains of Clostridium botulinum produce seven serotypically distinct
neurotoxins (BoNTs); all serotypes interfere with neural transmission by
blocking the release of acetylcholine in cholinergic neurones. On the basis
of the analgesic properties of cholinergic drugs, the use of BoNts may be
considered as an alternative to study the functional role of cholinergic
system on pain, with the advantageous prerogative of their selective and
reversible action. Although the peripheral effects of BoNTs are extensively
documented, their effects on the central nervous system are much less clear.
We have investigated, in mice, the central effects of two BoNTs isoforms
on inflammatory pain. To evaluate the mechanisms involved in the action
of the neurotoxins, the interaction with other neurotrasmitter systems, e.g.
the glutamatergic system, has also been examined. Our results show for the
first time a central effect of BoNTs and suggest BoNT/A as useful tool in
the experimental studies aimed at the comprehension of the mechanisms of
inflammatory pain.
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BEATRICE SOFAER
Clinical Research Centre, University of Brighton, UK.
30
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Abstract
PRACTICAL ISSUES FACED BY OLDER PEOPLE WHO SUFFER CHRONIC PAIN: SOME
SIMILARITIES AND DIFFERENCES BETWEEN MEN AND WOMEN
B. Sofaer, A.P.Moore, I. Holloway, J.M. Lamberty, J. O'Dwyer
Introduction A fifth of the population in the UK is over 60. Between 1995 and 2025 the number of people over the
age of 80 is set to increase by half. Chronic pain adversely affects older people because of the numerous disabilities
that affect people in later life.
Background and Aim Much of the literature on chronic pain has focused on measuring associated attributes and
beliefs. Some attention has been given by researchers to the personal experience of pain and the meaning it has for the
sufferer. There appears to be a paucity of literature on the practical issues faced by older people experiencing chronic
pain.
The aim of this study was to explore the practical problems faced by older people attending two pain clinics in the
South East of England.
Method Sixty three people over the age of sixty years and their spouse, partner or carer were interviewed at home as
part of a qualitative study to ascertain the practical difficulties they faced from day to day in relation to being in pain.
The interviews were transcribed and analysed using thematic analysis.
Results Forty two women and 21 men participated. All participants expressed frustration about their lack of mobility
and inability to perform many activities. Several resented having to wait for help while suffering pain, knowing that
they were in their twilight years.
Striving to maintain independence was one of the main themes identified. Within this theme there was a variety of
strategies used in an effort to overcome being disabled by chronic pain, including the use of a plethora of practical
items.
Learning to pace daily activities and trying to avoid social isolation were important for both men and women.
Some differences were identified between male and female respondents; ‘looking good and feeling good’ was
particularly important for women and was seen as part of boosting self-esteem, whereas finding a new role in life was
seen by many men as important for them in maintaining self- esteem.
Almost all respondents reported that helping other people was an important factor in boosting their own morale, but
whereas women offered a supportive role to others or carried out charitable work, men found satisfaction in carrying
out practical tasks for other people.
The results provide insights into the practical and social issues experienced by older people who suffer chronic pain
and are supported by quotations from the participants.
Implications Older patients should gain a better understanding of managing chronic pain. Health care professionals
should gain increased understanding about the needs of older people in relation to management of chronic pain.
The data generated from the interviews was used to inform the development and publication of a booklet specifically
for older patients suffering chronic pain.
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IRINA P. BUTKEVICH
I.P. Pavlov Institute of Physiology of the Russian Academy of Sciences
31
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
St. Petersburg, Russia.
abstract
SEX DIFFERENCES IN HPA AXIS AND PAIN
Our previous work has demonstrated the increase of formalin-induced pain
in prenatally stressed rats and revealed sex and age differences in effects of
prenatal stress. In the present study we evaluated formalin-induced pain and
the plasma level of corticosterone (C) in prenatally stressed (PS) and non
stressed (NPS) 25-and 90-d-o male and female rats born to dams subjected
to bilateral adrenalectomy (ADX) and sham (SH) operation. Bilateral ADX
in adult females about 3-4 weeks ahead of coupling is an approved method
for exception in the blood of pregnant dam of stress raising corticosteroids
which is considered to underlie impairments of organism’s functions in
postnatal ontogeny. It was found that differences in effects of formalin and
saline (control) injections in 25-30 min on C are more pronounced in
offspring of ADX dams. There were much more differences in both C and
indices of formalin-induced pain in 90- than 25-d-o rats. In 90-d-o females
formalin-induced pain activated the hypothalamo-pituitary-adrenal axis
(HPA) to a greater extent than in males. In this age effects of ADX clearly
manifested themselves in flexing+shaking that was fewer in number in
ADX than in SH females, but greater in ADX than in SH males. There were
no differences between ADX PS and SH PS in both females and males.
Licking duration was significanty greater in females than in males. Sex
differences were found in ADX PS, SH PS and SH. Thus, sex and age
differences are revealed in activation of HPA system by formalin-induced
pain in prenatally stressed rats. Changes in C do not always correlate with
behavioral response to formalin
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SYLVIE MULTON
Laboratoire de Neuro-Anatomie Université de Liège - Belgique
32
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
ESTROGEN AND PAIN: STUDY IN AROMATASE KNOCK-OUT
MICE USING THE FORMALIN MODEL
In order to study the role of gender and estrogens on inflammatory pain, we
compared sensitivity to formalin injected in the lip between male and
female estrogen-deficient aromatase knock-out mice (ArKO) and their
wild-type littermates (WT). No difference in nociceptive behaviour was
observed between male and female WT mice. By contrast, lip rubbing was
significantly more pronounced in ArKO than in WT females during the
second “tonic” pain phase. ArKO males did not differ significantly from
their WT littermates regarding phases 1 and 2, but they displayed a third
phase of pain behaviour 36 minutes after the formalin injection.
Furthermore, the influence of inflammatory pain on estrogen receptor
(ERα) expression was assessed by immunohistochemistry in the trigeminal
nucleus caudalis in those mice. Four hours after formalin injection, a
significant down-regulation of the receptors expression appeared in WT
female mice in laminae I-III of the injected-side while an inversed tendancy
was observed in males WT. ER expression was not changed in ArKO
males and females mice.
Altogether, our results confirm estrogen role in pain modulation in male
and female mice, their total absence having globally a pro-nociceptive
effect but also suggest that underlying control mechanisms of pain differ
between both sexes.
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ABOLHASSAN AHMADIANI
33
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Dept. of Pharmacology, University of Medical Sciences, Teheran, Iran.
abstract
GONADAL STEROIDS AND PAIN
It is more than two decades that conflicting reports have been published on
the relationship between sex steroids and pain. It has also been shown that
morphine affect the synthesis of testosterone, which can be explained
unclearly by the existance of a loop between endocrine hormones and
opioids. these findings are stretched to the role of steroids in the induction
of morphine dependence and tolerance. Since the precursors and enzymes
necessary for the synthesis of neurosteroids exist abundantly in the CNS, it
was postulated that steroids e.g. testosterone could be synthesized in CNS
regardless of gonads. We evaluated the effect of testosterone on chronic
pain using microdialysis and behavioral techniques and we showed a
connection between spinal serotonin (5HT) and the analgesia induced by
the elimination of testosterone.
We also demonstrated that testosterone was a neurosteroid and discussed a
new possible mechanism by which morphine affected the amount of
testosterone produced in CNS. We suggest that: 1) the brain and spine
synthesis of testosterone is independent of the gonads, 2) its reduction in
the neurons and plasma is a defensive mechanism in pain and 3) its
reduction after morphine treatment is due to the increased activity of 5alpha-Reductase.
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MARY FORSLING
34
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Neuroendocrine Laboratories, GKT School of Medicine,
Guy’s Campus Lodon Bridge. London , UK
abstract
PAIN AND NEUROENDOCRINOLOGY IN PARTURITION
Release of anterior pituitary hormones is stimulated during parturition. The
neurohypophysial system, producing oxytocin and vasopressin, is also
activated, oxytocin contributing to the delivery of the fetus. The release of
oxytocin and vasopressin is stimulated by stress including pain. Research
has indicated that males and females differentially experience pain with the
female being more susceptible. Evidence suggests that sex hormones
mediate differences in pain perception. Release of neurohypophysial
hormones is also modulated by ovarian steroids, suggesting their release in
response to noxious stimuli would depend on reproductive status. Initial
studies on the oestrous cycle of the rat were consistent with this hypothesis,
the animals having the lowest threshold to a painful stimulus at proestrus, a
time when the vasopressin response was greatest. Animal studies confirm
an increase in the pain threshold during parturition via spinal opioid
mechanisms modulated by oestrogen and progesterone. This may act as
negative feedback on oxytocin as stress is known to delay delivery.
However increased vasopressin concentrations are associated with difficult
labour. Pain thresholds are altered in lactation as is the formalin-induced
release of oxytocin and vasopressin in the rat. Interestingly the response
was smaller in animals having undergone a previous pregnancy.
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ANTONELLA CIARAMELLA
Pain Therapy and Palliative Care Unit, Azienda Ospedaliera Pisana, Pisa, Italy
35
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
DOES PSYCHOPATHOLOGY INFLUENCE THE DIFFERENT
PERCEPTION OF PAIN BETWEEN SEX?
The first part of this presentation will deal with a brief summary of preexisting research about the influence of psychopathology in the different
perception of pain between sex in clinical and experimental settings.
In the second part, results from our research both in clinical and
experimental contexts will be discussed.
Regarding the clinical studies two different methodologies will be
compared: psychopathological self rating scales and the assessment of
psychopathology according to DSM IV criteria. Using the SCL 90 rating
scale results show a difference between sex in a) some dimensions of
psychopathology (somatization, depression, anxiety and psychotic
symptoms) and b) Melzack and Casey theory dimensions of pain (Sensorial
and Affective). However using a multivariate regression model analysis the
psychopathological and pain relationship between sex are independent
variables, confirming pre-existing results. Also using DSM IV criteria in
some psychiatric disorders a difference was found between sex. Moreover,
intensity and affective dimension were different between sex in about 200
chronic pain subjects of this study.
In the experimental setting the influence of psychopathology in the
different perception of pain between sex was investigated comparing pain
free with chronic pain subjects.
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SERGE MARCHAND
Faculté de Medicine, University of Sherbrooke, Sherbrooke, Canada.
36
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
THE ROLE OF SEX HORMONES ON PAIN MODULATION:
FROM ANIMALS TO HUMAN STUDIES
The role of sex hormones on endogenous pain modulation mechanisms
plays a key role in explaining the differences in pain perception between
men and women. Recent results support that it may also play an important
role in the gender dependant prevalence of certain chronic pain conditions.
During this talk, we will present data from formaline induced nociceptive
responses in rat to endogenous pain inhibition in humans supporting that
view. The influence of sex hormones in different modulation mechanisms
will be discussed, including the role of odors on pain perception and the
role of sex hormones levels in some chronic pain conditions that are more
frequent in women than in man (fibromyalgia, irritable bowel). Autonomic
activity derived from electrophysiological data including electrocardiogram
and galvanic skin responses (ECG and GSR) linking our findings in chronic
pain and an effect on autonomic responses will also be discussed.
The final goal of this presentation is to underline the importance of
understanding the influence of sex hormones on endogenous pain
modulation mechanisms and their effect on some chronic pain conditions.
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____________________________________________________________________________________
FRANCO MONGINI
Dept. Clinical Pathophysiology , Headache and Facial Pain Unit,
37
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
University of Turin, Turin Italy,
abstract
PSYCOLOGICAL ASPECT OF MIGRAINE AND OTHER
HEADACHE TYPES IN WOMEN AND MEN
Distinctive personality traits are observed in patients with specific head
pain pathologies. Patients who suffer from frequent migraine show
elevations of MMPI and STAI scales. In chronic headache an “emotionally
overwhelmed” profile (with elevation of several scales), or a conversive
profile (with elevation of hypochondria and hysteria, depression being
somewhat lower) are frequent . The prevalence of anxiety and depression
disorders is high. After treatment a score decrease of many MMPI scales is
observed. However, conversive traits may still be present at a lower level in
migraine patients. Chronic migraine and chronic tension type headache are
also characterized by different pattern of pain sensation. High levels of the
affective dimension prevail in chronic migraine. The co-occurrence of
psychiatric disorders and personality changes in migraine does not appear
to influence the results of treatment at short term, but it seems to be
influential on the headache history in the long term. In these patients
psychiatric disorders considerably increase the level of muscle tenderness
in the head and, even more, in the neck: this might facilitate the evolution
into chronic migraine. In women with different headache types before
treatment several MMPI scores are higher than in men but tend to improve
more consistently after treatment.
____________________________________________________________________________________
____________________________________________________________________________________
VICTORIA GRACE
38
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
College of Arts, University of Canterbury, Christchurch, New Zealand.
abstract
CHRONIC PELVIC PAIN: GENDER AND MEANING
Victoria Grace and Sara MacBride-Stewart
Chronic pelvic pain in women is often unable to be explained in biomedical
terms, and tests the limits of a biomedical model. There is a concern to
develop approaches to understanding chronic pain that overcome the
problems inherent in a rigid mind/body dualism. Dualist models that
postulate the distinction between biological and socio-psychological
phenomena in absolute terms fail to produce cogent explanations of chronic
pain. Questions surrounding meanings individuals ascribe to their
experience of chronic pain are opening up new lines of inquiry and new
models of understanding at the interface of medicine and the social
sciences. This research reports the results of an empirical study of the
meanings women generate in association with their experience of chronic
pelvic pain (not associated with sexual activity or menstruation),
dysmenorrhoea and dyspareunia. Discourse analytic methods are used to
analyse narratives produced through in-depth interviews with 40 New
Zealand pakeha women (of European descent). Critical phenomenological
approaches inform the research. In particular the paper explores the
significance of gender.
____________________________________________________________________________________
____________________________________________________________________________________
STEFAN LAUTENBACHER
39
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Physiological Psychology, Otto-Friedrich-University of Bamberg, Bamberg,
Germany
abstract
SEX-RELATED DIFFERENCES IN THE
MECHANISM OF PAIN MODULATION
PSYCHOLOGICAL
The study of sex differences in pain perception has arrived at a stage when
mere description is no longer sufficient but the quest for the mechanisms of
action has started. On the psychological sex-related differences in anxiety
anticipating and accompanying pain, perceived threat thru pain, gender role
expectations towards pain and attentional control of pain have recently
gained interest. The author will review the available literature and add
experimental data from his own laboratory on sex differences in the
attentional control of pain
____________________________________________________________________________________
____________________________________________________________________________________
JOEL D. GREENSPAN
Dept. of Biomedical Sciences, Univ. of Maryland Dental School – Baltimore,
40
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
USA
Abstract
SEX DIFFERENCES IN THE FUNCTIONAL MRI RESPONSE TO PAINFUL
HEAT
Eric A. Moulton, Michael L. Keaser, Rao P. Gullapalli, and Joel D. Greenspan*;
Program in Neuroscience, and Research Center for Neuroendocrine Influences
on Pain, Univ. of Maryland, Baltimore, MD, USA.
A few neuroimaging studies have reported significant sex differences in painrelated brain activation, although results are not altogether consistent across
studies. We sought to identify sex differences in the fMRI-measured response to
painful contact heat stimuli in a large sample of subjects (19 women, 14 men).
One innocuous and two painful levels of stimuli were used. The noxious heat
stimuli were adjusted to evoke comparable pain intensity ratings across subjects
- a "slightly painful" and a "moderately painful" level. Using a GLM-based
analysis on a subject-by-subject basis, several components of the "pain matrix"
contained significantly activated clusters in almost all subjects. The sizes of
significantly activated clusters showed large intersubject variability, such that
voxel counts were not significantly different between men and women in any
ROI. The fMRI signal intensity amplitude of the nociceptive-related response
(i.e., the "moderately painful" response minus the innocuous response) was
significantly greater for men in contralateral S1, contralateral anterior insula,
mid-ACC, and perigenual ACC, as well as borderline significant in the inferior
frontal gyrus. No significant sex differences were found for S2 or posterior
insula, despite trends in the same direction. Thus, in most pain-related cortical
regions, the fMRI signal amplitude was greater in men vs. women in response to
painful heat, despite comparable pain intensity ratings. The biological
significance of these differences remains to be determined. Future studies
involving functional neuroimaging of pain should consider the sex of the subject
as a factor in study design. (Supported by NIH grants P50 AR-49555 and R01
NS-39337.)
__________________________________________________________________________________
____________________________________________________________________________________
POSTER
ANNA MARIA ALOISI
41
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Department of Physiology, University of Siena, Via Aldo Moro, 53100 Siena, Italy
abstract
GONADECTOMY AFFECTS HORMONAL AND BEHAVIORAL
RESPONSES TO REPETITIVE NOCICEPTIVE STIMULATION IN
MALE RATS
Aloisi Anna Maria*, Ceccarelli Ilaria and Fiorenzani Paolo
Sex differences have repeatedly been observed in chronic pain syndromes
in both humans and animals, with females showing a higher incidence; it is
likely that the gonadal hormones are responsible for these differences. To
examine the role of male gonadal hormones on repetitive nociceptive
stimulation, we studied male rats, half of them gonadectomized (GDX) and
half left intact (INT). Starting from the third week after gonadectomy, they
formalin 5% injected s.c. in the dorsum of the hind paw: right, left and
right). Formalin-induced licking, flexing and jerking of the injected paw
were recorded and analyzed for each of the three trials. Analysis of
Variance showed significant differences between GDX and INT animals
depending on the trial considered: Trial 1: the GDX and INT groups
showed a similar amount of licking, flexing and paw-jerk; Trials 2 and 3:
these responses showed a sort of adaptation in INT animals, not present in
the GDX ones, resulting in lower levels of pain responses in INT than
GDX. Corticosterone was higher in GDX animals than INT ones.
Testosterone plasma levels were drastically decreased by gonadectomy,
while estradiol was increased. These data indicate that male gonadal
hormones play a key role in inhibiting the behavioral responses to repeated
nociceptive stimulation. This suggests that the lower incidence of chronic
pain syndromes in males could be due to the presence of these hormones.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
EMILIO BATTISTI
42
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
TAMMEF CENTRE- University of Siena,
C.I.R.D.I.B.- University of Siena, Italy
Italy
abstract
EFFICACY OF A MUSICALLY MODULATED ELECTROMAGNETIC
FIELD (TAMMEF) IN THE TREATMENT OF CHRONIC LOW BACK
PAIN. Battisti E., *Piazza E., Bianciardi L°., Rigato M., Giordano N.
Background: Numerous studies have demonstrated the utility of extremely low
frequencies (ELF) electromagnetic fields in the treatment of pain.
Moreover, the effects of these fields seems to depend on their respective codes
(frequency, intensity, waveform).
Purpose of the study: In our study we want to value the effects of the
TAMMEF (Therapeutic Application of a Musically Modulated
Electromagnetic Field) system, which field is piloted by a musical signal and
its parameters (frequency, intensity, waveform) are modified in time, randomly
varying within the respective ranges, so that all possible codes can occur during
a single application.
Ninety subjects, affected by chronic low back pain, were enrolled in the study
and randomly divided into three groups of 30 patients each: A exposed to
TAMMEF, B exposed to ELF, C exposed to a simulated field. All subjects
underwent a cycle of 15 daily sessions of 30 minutes each and a clinical
examination upon enrolment, after 7 days of therapy, at the end of the cycle
and at a follow-up 30 days later.
Results: All the patients of groups A and B completed the therapy without the
appearance of side effects: they presented a significant improvement of the
subjective pain and the functional limitation, which remained stable at the
follow-up examination. In group C, there was no improvement of the pain
symptoms or articular functionality.
Conclusions: This study suggests that the TAMMEF system is efficacious in
the control of pain symptoms and in the reduction of functional limitation
in patients with chronic low back pain. Moreover, the effects of the TAMMEF
system cover those produced by the ELF field.
Key words: electromagnetic fields, therapy, low back pain, TAMMEF.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
AMALIA DI GIANNUARIO
Department of Drug Research and Evaluation –
43
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Istituto Superiore di Sanità, Rome. Italy.
abstract
ORPHANIN/FQ BLOCKED THE TOLERANCE TO THE
ANTINOCICEPTIVE EFFECT OF MORPHINE.
Amalia Di Giannuario, Stefano Fidanza, Adriano Urciuoli, Stefano
Pieretti.
The development of tolerance in response to chronic use of drugs is a
characteristic of all the opioid analgesics and one the major problems in
their clinical use (1). It has been suggested that the reduction of morphine
analgesia during chronic treatment is mediated by an increased
compensatory activity of anti-opioid peptides and the endogenous ligand
for opioid-receptor-like OP4 receptor, named orphanin FQ /nociceptin is a
possible candidate (2). Although orphanin shows homology with dynorphin
A, it lacks affinity for traditional OP1, OP2, and OP3 opioid receptors and
exerts anti-opioid activity. Since intracerebroventricular (i.c.v.)
administration of orphanin reduces opioid-induced antinociception (2), we
evaluated whether repeated administration of orphanin (0.25-0.5 nmol i.c.v.
for 5 days) influenced the tolerance to the antinociceptive effect of
morphine (7 mg/kg intraperitoneally i.p. for 5 days) in mice, by using the
hot-plate test. A maximal antinociceptive response appeared on day 1, 30
min after morphine administration. This effect decreased progressively
from day 3 to 5 reflecting the development of opioid tolerance. Chronic
administration of orphanin did not by per se modify the nociceptive
threshold. Orphanin administered on day 1 with morphine reduced the
antinociceptive effect of morphine exhibiting anti-opioid activity. However
tolerance to this orphanin anti-opioid effect appeared on day 3, when the
peptide was able to block the development of tolerance to the
antinociceptive effect of morphine. Our results suggested that tolerance to
anti-opioid activity of orphanin might control opioid antinociception.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
JOEL D. GREENSPAN
Dept. of Biomedical Sciences, Univ. of Maryland Dental School - Baltimore
44
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
CENTRAL NOCICEPTIVE PROCESSING DIFFERENCES
RELATED TO SEX AND TEMPOROMANDIBULAR DISORDERS
Eleni Sarlani, Edward G. Grace, Mark A. Reynolds, Joel D. Greenspan.
This study assessed differences in temporal summation (TS) of mechanically
evoked pain, and aftersensations following repetitive noxious stimulation,
between TMD patients and controls, and between healthy females and males.
TS, the increase in pain intensity with repetitive noxious stimulation, is
thought to reflect transient upregulation in central processing of nociceptive
input. Sixteen series of 10 repetitive, mildly noxious, sharp, mechanical
stimuli were applied to the fingers of 25 TMD patients, 25 healthy females,
and 25 healthy males. The subjects rated the pain intensity and
unpleasantness evoked by the 1st, 5th and 10th stimulus in the series, and
aftersensations 15sec and 1min after the last stimulus. Data were analyzed by
3-way ANOVA. Pain and unpleasantness ratings increased with repetition
(p<0.0001). TMD patients exhibited greater temporal summation of pain and
unpleasantness (p<0.001), stronger aftersensations (p<0.005), and more
frequent painful aftersensations (p<0.05) than controls. Healthy females
showed greater TS of pain intensity and unpleasantness (p<0.0001), higher
intensity and unpleasantness of aftersensations (p<0.0005), and more
frequent painful aftersensations (p<0.05) than males. Greater TS of pain and
aftersensations from digital stimulation of TMD patients vs. controls suggest
a generalized hyperexcitability of the central nociceptive system in this
patient group. Such hyperexcitability may contribute to the pathophysiology
of TMD pain. Moreover, greater TS of pain and aftersensations in healthy
females than males indicate that their central processing of nociceptive input
may be more easily upregulated into pathological hyperexcitability, possibly
accounting for the predominance of TMD among women. (Supported by NIH
grants P50-AR49555 and RO1-NS39337).
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
MOHAMMADREZA HEIDAR
Sari School of Pharmacy, Medical Sciences University of Mazandaran,
45
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Sari, Iran
abstract
ANTINOCICEPTIVE EFFECT OF GLAUCIUM
PAUCILOBUM EXTRACT AND TOTAL ALKALOIDS IN
RATS
The species of Glaucium have been used in Iranian herbal medicine as
laxative, hypnotic, antidiabetic agents and also in the treatment of
dermatitis. The probable analgesic effect of extract of aerial parts of
Glaucium pacilubom (G.P) Boiss and Huet (papaveraceae), a native
plant of Iran were studied using acute and chronic (formalin test) pain
models of rats. The intrapreatonial (i.p) administration of (G.P)
extract at the doses of 50,60,70 and 80 mg/kg caused graded
inhibition of pain in early and late phases of formalin test. The extract
at the doses of 50 to 80 mg/kg significantly raised the pain threshold
at an observation time of test in comparison with control (p<0.05).
The (i.p) administration of (G.P) total alkaloid at the doses of 10, 20,
30, 40 and 50 mg/kg also inhibited both phases of formalin induced
pain. The extract at the antinociceptive doses did not affect motor
coordination of animals when assessed in the rotarod model.
topics Keyword: Glaucium paucilobum - Formalin test Antinociception - Rat . pharmacology
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
YONG-CHUL KIM
Dept. of Anesthesiology and Pain Medicine Seoul National University College of Medicine
Faculty of Pain Clinic - Seoul National University Hospital, Seoul, Corea
46
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
THE EFFECT OF EPIDURALLY-ADMINISTERED HYALURONIC
ACID IN A RAT FORAMINAL STENOSIS MODEL
Woo-Seok Sim, Young-Jin Lim, Pyung-Bok Lee, and Yong-Chul Kim
Background: Hyaluronic acid (HA) is a naturally occurring polysaccharide that
has been shown to be beneficial in various clinical settings such as intra-articular
injection and has anti-inflammatory, anti-adhesion, and concussion-deadening
effects. This study was designed to evaluate the effect of epidurally-injected HA
as an agent for decreasing pain in an animal model of chronic compression of
dorsal root ganglion.
Methods: In the first study, trial drugs were administered epidurally 3 days after
the operation in saline group (n = 20), HA group (n = 23), or no treatment
(control) group (n = 10) in the model. In the second study, trial drugs were
administered epidurally 8 days after the operation in saline group (n = 12), HA
group (n = 16), or control group (n = 9). In the saline and HA groups, 0.1 ml of
0.9% normal saline and of HA were injected into the epidural space through the
epidural catheter, respectively. Mechanical and thermal withdrawal tests and
motor dysfunction were evaluated for five weeks after the epidural injection.
Results: On both the immediate (up to 4th postoperative hours) and delayed (from
1st to 35th postoperative days) evaluations, the mechanical withdrawal threshold
was recovered in the HA injected group regardless of injection time. However, in
both the saline and control groups, the mechanical hyperalgesia did not recovered.
The results on the thermal withdrawal threshold showed similar tendency to the
mechanical withdrawal test.
Conclusions: Our findings suggest that the epidurally-administered HA may be
effective for the relief of pain produced by chronic compression of dorsal root
ganglion in the clinical settings such as spinal stenosis and failed back surgery
syndrome.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
MASSIMO MEARINI
Neurosurgical Clinic, Brescia University, Brescia, Italy
47
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
FOUR LIMBS DISTAL NEUROPATHYC PAIN LYME’S DESEASE
RELATED,
TREATED WITH CERVICAL AND DORSO-LUMBAR
DOUBLE CHANNEL SPINAL CORD STIMULATION
M. Mearini MD*, C. Cornali MD, C. Barazzetti MD, S. Podetta MD, C.
Ferlinghetti MD, E. Catenacci MD.
Lyme’s desease is caused by Borrelia, a bacterium transmitted by mints. A slow
developing encephalopathy or an axonal polineuropathy with distal parestesia and spinal or
radicular pain can rarely appear.
We report the case of a 45 years-old woman, affected by Lyme’s Desease (W.B. Borrelia
Garinii antibodies positiveness) whose first clinical manifestation, 7 years before, was
characterized by feet cold disestesia evolved in about 12 months toward a distal parestesic
syndrome with irrepressible neuropathyc pain to the four limbs, with normal EMG and
Doppler.
Pain became intolerable, particularly at rest, unresponsive to any drugs. The patient could
sleep only 10-15 minuts per night. Normal social activities were impossible.
After 8 years from the first symptoms, it was decided to effect a therapeutic attempt with
SCS, following these procedures:
 percutaneus positioning of median epidural electrode D12 with evoked parestesia to
both the distal inferior extremities and stimulation test for 2 weeks with excellent
result;
 then percutaneus positioning of median cervical epidural electrode C6-C7 and
stimulation test for 2 weeks with excellent result. In the meantime the lumbar test
continued always maintaining the initial result;
 in accordance with these favorable tests, we proceeded to the third session in which
the cervical and lumbar electrodes were connected to a double independent channel
ANS-Genesis neurostimulator, positioned in subcutaneus paravartebral lumbar region.
Cervical and dorso-lumbar stimulations were programmed with distinguished
parameters, both in continuous.
Now, after 18 months, the analgesic result is excellent, with an almost complete subjective
pain relief, without any drug assumption. Patient’s compliance is very good. She
recovered her normal nighttime sleep and social relationships.
Technical problematics did not occur.
We have not found in literature analogous cases treated with SCS. We thought that the
neuropathyc characteristic of the pain and the absence of valid alternatives could justifie
the attempt. This has been comforted by a really meaningful and lasting result.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
STEFANO PIERETTI
Department of Drug Research and Evaluation Italian National Institute of Health
48
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
Rome, Italy
abstract
THE INVOLVEMENT OF FORMYL PEPTIDE RECEPTORS
(FPRs) IN INFLAMMATORY PAIN: THE EFFECTS OF FPRs
AGONISTS IN THE FORMALIN TEST IN MICE
S. Pieretti, A. Di Giannuario, A. Dalpiaz, G. Vertuani
The receptors for formilated peptides (FPRs) belong to the G proteincoupled receptors family, three members of which have been cloned so far
in human tissues and cells (Le et al., Trends Immunol 2002; 23:541-548)
and with six genes, that at least three translated into protein, have been
identified in mice (Gao et al., Genomics, 1998; 51: 270-276). The FPRs
agonist formyl-MLF (fMLF) is one of the first identified FPR ligand but a
number of novel peptide agonists has recently been identified that activate
the FPRs (Le et al., 2002). Some of these - as the agonist formyl-MIFL
(FTM) and formyl-MIFL-OMe (FTO) - are more potent agonist than fMLF
(Dalpiaz et al.,. Eur. J. Pharmacol. 2001; 411:327-333). Until recently, it
has been thought that FPRs are specifically expressed in neutrophils and
monocytes where they potently modulate chemotaxis (Le et al., 2002).
However, the presence of FPRs has been demonstrated in different
nonhematopoietic cells, such as hepatocytes, dendritic cells and microglial
cells suggesting that FPR agonists may influence cellular mechanisms other
that the inflammatory response (Le et al., 2002).
Recently, we reported the involvement of FPRs in inflammatory pain
(Pieretti et al., Pain 2004; 109:52-63). So the current study was undertaken
to increase our knowledge on the role of FPRs in nociception, and we
administered FTM and FTO in mice performing the formalin test. We
found that the formyl peptide receptor agonists fMLF and FTM induced
antinociceptive effects in the formalin test both after peripheral and central
administration. On the contrary, FTO did not change formalin-induced
effects. The antinociceptive effects induced by fMLF and FTM were
blocked by the FPRs antagonist Boc-MLF (Boc1). These results indicate
that exogenously administered FPRs agonists can peripherally and centrally
inhibit the nociceptive transmission associated with inflammatory processes
through a mechanism that involves formyl peptide receptors.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
MOHAMMAD B. ROKNI
49
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
PhD in Parasitology. Dept. Medical Parasitology, School of Public Health,
Teheran University of Medical Sciences, Teheran, Iran
abstract
THE ROLE OF PAIN IN DIAGNOSIS THE PARASITIC INFECTIONS
In general, most parasitic infections in serene cases encompass no pain or show
a moderate one. Pain in intestinal parasitic infection such as giardiosis,
cryptosporidiosis, trichinosis, strongyloidiasis and so on, is generally blurred or
imprecise epigasteric one with nausea and vomiting.
This kind of pain is allied to duodenitis and jejunitis provoked by these
infections. In most of the cases there is need to complimentary documents to
assign a pain specifically to a parasitic infection. For example an abdominal
pain localized to the right hypocondrium or epigastrium must be accompanied
by a history of eating aqueous vegetables to allocate it to fasciolosis, or an
acute pain in right upper quaderam suspected to opistorchiasis must be
confirmed by detecting if the patient has eaten raw fish or not. Some times a
sever pain indicating obstruction in ascariasis may be indicative. Parasites are
resident in most of the parts of the body;
hence it is expected to witness pain throughout the body. Muscle pain in
trichinosis, headache and abdominal pain in shistosomiasis, chest pain in
paragonimiasis, intense griping pain similar to epigastritits in the morning
which is relieved by food in fasciolopsiasis buski, colicky pain and tenderness
in heterophiasis are such. In conclusion, pain in parasitic infection is merely a
supplementary marker to help the physician to diagnose the disease and can not
be regarded as a problem-solving indicator.
Keywords: pain- parasitic infections- diagnosis- intestinal parasites
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
IVAN SMILOV
Department of Anesthesiology and Intensive Care Medicine;
50
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
University hospital of Obstetric and Gynecology, Sofia, Bulgaria
abstract
INFUSION WITH DEXMEDETOMIDIN HCL (PRECEDX) AND INFUSION
WITH PARECOXIB SODIUM (DYNASTAT) FOR POSTOPERATIVE PAIN
RELIEF AND SEDATION IN GYNECOLOGY
Smilov I., D. Uzunova, S. Georgiev, N. Faitondjieva
Background and Goal of study: The aim of our study is to find a method with better
analgesic and sedative results and fewer adverse effects, which can be easily used for the
postoperative treatment in Gynecology.
Material and Methods: After institutional approval 60 ASA I-II patients, undergoing
elective gynecological operations were randomized in two groups. The groups were
similar in age, weight and type of operations. All patients received the same induction
and maintenance of anesthesia – group A (n=30) and group B (n=30). In all groups the
infusions started after the extubation and transfer to the postoperative care unit for 12
hours at Ramsay  2 and VAS  5. In group A the patients received a loading dose of
Precedex 1 mcg/kg/h for 10 min, followed by maintenance infusion rate of 0,2-0,7
mcg/kg/h. Group B received 40 mg Dynastat i.v. bolus, followed by infusion of Dynastat
with rate 3,2-4,0 mg/h up to 80 mg per day. Visual analogue scale (VAS) was used for
postoperative pain degree (0-10). The sedation level was assessed using Ramsay-scale.
Pain intensity, heart rate, respiratory rate, arterial pressure, sedation and incidence of
adverse effects of drugs were assessed. The statistical analysis was performed by
Student, s t-test, Mann-Whitney U-test and Kolmogorov-Smirnov test.
Results and Discussion: Satisfactory analgesia was obtained by group B (VAS = 2.6),
in group A 20 % of patients required additional pain relief medication. The good level of
sedation was achieved in group A (Ramsay = 3,3), in group B by 30% of patients was
applied sedative medication. Only one patient in the group A experienced significant
hypotension (MAP=60) and required additional medication (Ephedrine = 10 mg i.v.)
Conclusion: The infusions of Dynastat and Precedx were safe and effective for
postoperative analgesia and sedation in gynecological surgery.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
ABE SUMIKO
Department of Legal Medicine
Fukushima Medical University School of Medicine, Japan
51
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
abstract
INDUCTION OF NERVE GROWTH FACTOR EXPRESSION IN A
RAT DORSAL ROOT GANGLION AFTER APPLICATION OF A
TOURNIQUET
Sumiko Abe, Ikubumi Mizusawa, Miwako Suto, Naho Katoh, Takashi
Honda, Kouichi Hiraiwa
We investigated the mRNA levels of neurotrophins and neurotrophin
receptors in a rat dorsal root ganglion (DRG) after tourniquet application to
a hind limb to identify the nerve-protective molecules that are induced
immediately after peripheral nerve crush and play a part in the process
leading to secondary events. No significant expression of nerve growth
factor (NGF) mRNA or protein was observed in the control or contralateral
DRG. NGF mRNA expression started within 2 h and then NGF protein
expression was observed in Schwann cells at 4 h after application of the
tourniquet. The levels of neurotrophin 3 (NT3) mRNA were significantly
increased in the DRGs on both sides at 1 and 2 h after tourniquet
application, but no significant changes in brain-derived neurotrophic factor
and neurotrophin 4/5 expression levels were observed in either the
contralateral or ipsilateral DRG. The expressions of NGF and NT3 mRNAs
might be an acute response to protect DRG neurons that have lost materials
provided by retrograde axonal transport from the target organs at the early
stage of nerve injury. The expression levels of neurotrophin receptors in the
DRGs on both the contralateral and ipsilateral sides had decreased at 1 to 2
h after application of the tourniquet and had returned to the control levels at
4 h after tourniquet application. It is possible that the inflammatory
mediators produced locally in the limb circulate systemically and mediate
the initial decrease in neurotrophin receptor expression levels.
We also examined the mRNA levels of c-fos in a rat brain at 6 h after
tourniquet application to a hind limb. The expression level of c-fos mRNA
significantly increased after tourniquet application, suggesting that
continuous neuronal excitation that arises from pressed sciatic nerve leads
to a rapid induction of c-fos mRNA expression in the brain.
____________________________________________________________________________________
____________________________________________________________________________________
POSTER
SALVATORE CRISCUOLO
U.O.C. Post-operative Therapy of pain, Siena University Hospital Siena
52
TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
FEMORAL-SCIATIC NERVE BLOCK WITH ELECTRICAL STIMULATION
AND SURFACE ELECTROMIOGRAPHY A NEW OPTION TO OPTIMIZE
ANAESTHESIA
Criscuolo S.$, De Martino A, Consiglio F., Staffieri C. and Zalaffi A.# *
Institute of General Surgery and Surgical Specialities,
Chair
of
Surgical
Pathology, $U.O.C. Post-operative Therapy of pain # DPT of Ophtalmological and
Neurosurgical Sciences
Background: peripheral nerve stimulation has been shown to produce a faster onset
and higher success rates of peripheral plexus and nerve block. In order to obtain a
quick and optimal needle positioning before anaesthetic injection and perfect control
of motor block, instead of the simple visual twitch control, surface electromyography
(EMG) techniques to register motor electrical activity have been used at our
institution.
Purpose: in order to see if our method could improve anaestesiological techniques we
compared a group of 5 awake patients undergoing lower limb surgery using the new
anaesthesiological peripheral block injection method, with a similar group of patient
that underwent the same surgical procedure with standard anaesthesiological
peripheral block methods. The differences in Pain Visual Analogue Scale (VAS)
changes and amount of drug used were studied.
Results: we didn’t found any difference in VAS in both groups but the amount of
carbocaine 1% necessary for a satisfactory block was significatively decreased in the
EMG guided group (500 mg in control and 250 mg in studied group).
Conclusion: the possibility to reduce the local anaesthetic doses appeared to be
extremely useful in patients at risk like those affected by cardiac and neurological
diseases.
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TRADITIONAL AND INNOVATIVE APPROACHES TO PAIN
The University of Siena and The Royal Society of Medicine
Siena, 16-19 September 2004
POSTER
ANTONIO DE MARTINO
Surgical Pathology , University of Siena, Siena Italy
DIAGNOSIS AND TREATMENT IN NEUROPATHIC PAIN AFTER SURGICAL HERNIA
REPAIR
A. De Martino, A. Zalaffi # *, G. Napoli, D. Cirianni, F.M. Consiglio, S. Criscuolo $
Institute of General Surgery and Surgical Specialities, Chair of Surgical Patology, $ U.O.C.
Post-operative Therapy of pain, # DPT of Ophtalmological and Neurosurgical Sciences
University of Siena – Italy
Background: Neuropathic postoperative pain affects surgical treatment of surgical hernia repair.
The countinuous increase in the incidence of patients with pain after hernioplastic Lichtenstein’s
could depends on several reasons: prosthetic material, fibrosis, technique variant, type of
anaesthetic block.
Purpose: In this pilot study we tested a new method that may permit to improve the diagnosis
and permit to treat the pain more precociously; the final task has been to decrease the role of
central sensibilization phenomena of post-operative pain. A quasi-experimental cohort of fourteen
patients (13 male, 1 female, range 45-78 year) was followed before and after our new pourposed
treatment. The inclusion criteria were: 1) a constant neurophatic postoperative pain on surgical
scar, with VAS score >5 in at least 3 measurement during the first 2 months after the operation.
2) no advantage, during this observation period, of several traditional drugs: FANS, opiate,
antiepileptic and antidepressant. After 2 months all patients were treated with a neurostimulator
with impulses of 0,1-0,3 mA, to point out cutaneous trigger points on surgical scar. Each trigger
point was infiltrated by a 1ml of solution of Ropivacaine 1% + depo-medrol 40mg. The
infiltration was repeated every 7 days, 5 times at most.
Results: Generally since the first infiltration the VAS score was reduces below 5. After the first
infiltration nine patients obtained a VAS score = 0-1; after the third infiltration patients obtained
a VAS score = 0-1; 2 patients obtained a VAS score = 3-4 after the fifth infiltration. The VAS
scores during the two following months significatively differed from those before the injection.
Also the oral analgesic consumpion of the whole group was significantly reduced after the
injection treatment.
Conclusion: Beside the small number of the patients studied in our group, the use of a
neurostimulation technique for the diagnosis and treatment of neuropathic pain allowed us to
obtain a better pain relief and a faster recover in quality of live of patients.
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