Download Modulation of pain

Anatomy
and physiology
of pain
Nociceptive Pain
Clinically, pain can be
labeled “nociceptive” if
it is inferred that the
pain is due to ongoing
activation
of
the
nociceptive system by
tissue injury.
Nociceptive Pain
Although
neuroplastic
changes (such as those
underlying
tissue
sensitization) are clearly
involved, nociceptive pain
is presumed to occur as a
result of the normal
activation of the sensory
system by noxious stimuli, a
process that involves 4
basic processes
 transduction
 transmission
 perception of pain
 modulation of pain
Nociceptors
Tissue injury activates primary afferent neurons
called nociceptors, which are small diameter
afferent neurons (with A-delta and C-fibers)
Nociceptors
Nociceptors respond to
noxious stimuli
Nociceptors are found in
 skin
 muscle
 joints
 and some visceral
tissues.
Nociceptors
Nociceptive primary afferent neurons are varied:
most are “silent” (may not respond to standard
stimuli, only than inflammatory substances are
present)
some are specific to one type of stimulus,
such as
- mechanical
- or thermal
but most are polymodal (respond to many
stimuli)
the number and size of the receptive fields
served by each fiber may be small or large,
respectively
Nociceptors
nociceptors free nerve endings has
capacity to distinguish between
noxious and innocuous stimuli when
exposed to
 mechanical (incision or tumor
growth)
 thermal (burn, ice)
 chemical (toxic substance) stimuli
 tissue damage occurs

substances are released by the
damaged tissue which facilitates the
movement of pain impulse to the
spinal cord
Substances released
The substances released from the affected tissue are:
 prostaglandins
 bradykinin
 serotonin
 substance P
 histamine
 protons
 NGF
The role of this substances provide opportunities for the
development of new analgesic drugs
Clinical significance
Non-steroidal anti-inflammatories, such as
ibuprofen, are effective in minimizing pain
because they minimize the effects of these
substances
released,
especially
prostaglandins .
Corticosteroids, such as dexamethasone used
for cancer pain, also interferes with the
production of prostaglandins.
Transduction
sufficient amounts of noxious stimulation
cause the cell membrane of the neuron (nervous
system cell) to become permeable to sodium
ions, allowing the ions to rush into the cell
and creating a temporary positive charge.
then potassium transfers back into the cell,
thus changing the charge back to a negative
one.
with this depolarization and repolarization, the
noxious stimuli is converted to an impulse
this impulse takes just milliseconds to occur.
Clinical significance
Some analgesics relieve pain primarily by
decreasing the sodium and potassium
transfers at the neuron level, thereby
slowing or stopping pain transmission.
Examples:
- local anesthetics,
- anticonvulsants used for neuropathic
pain, migraines.
Transmission
once depolarization
occurs,
transmission
of
information
proceeds proximally
along the axon to the
spinal cord and then
on to higher centers.
transmission across the first central synapse may
be influenced by activity in the primary afferent itself
and modulatory neural pathways.
that originate segmentally or supraspinally.
further modulation results from processes initated by
glial cells.
Transmission
impulse  spinal cord  brain stem  thalamus
 central structures of brain  pain is
processed.
neurotransmitters are needed to continue the
pain impulse from the spinal cord to the brain.
Transmission
Clinical
significance
Clinical significance
Clinical significance
Perception of pain
the end result of the neural activity
of pain transmission
it is believed pain perception
occurs in the cortical structures
- behavioral strategies and
therapy can be applied to
reduce pain.
brain can accommodate a limited
number of signals
- distraction, relaxation signals
may get through the gate,
leaving limited signals (such
as pain) to be transmitted to the
higher structures.
Perception of pain
Modulation of pain
The neurochemistry of these
processes involves an
extraordinary array of
compounds, including
- endorphins,
- neurokinins,
- prostaglandins,
- biogenic amines,
- GABA,
- neurotensin,
- cannabinoids,
- purines,
- and many others.
Modulation of pain
The endorphinergic pain modulatory pathways are
characterized by multiple endogenous ligands and different
types of opioid receptors: mu, delta, and kappa.
Endorphins are present in the periphery, on nerve endings,
immune-related cells, and other tissues,
Endorphins are widely distributed in the central nervous
system (CNS).
They are involved in many neuroregulatory processes
apart from pain control, including the stress response and
motor control systems.
Opioid drugs mimic the action of endogenous opioid ligands.
Most of the drugs used for pain are full mu receptor
agonists.
Modulation of pain
Other pain modulating systems, such as those that use
- monoamines (serotonin, norepinephrine and dopamine),
- histamine,
- acetylcholine,
- cannabinoids,
- growth factors
- and other compounds,
are targets for nontraditional analgesics, such as specific
- antidepressants and
- anticonvulsants.
It is likely that entirely novel analgesic compounds will
become commercially available in the future as drug
development programs target these systems.
Modulation of pain
changing or inhibiting pain impulses in the
descending tract (brain  spinal cord).
descending fibers also release substances such
as norepinephrine and serotonin (referred to as
endogenous opioids or endorphins) which have
the capability of inhibiting the transmission of
noxious stimuli.
cancer pain responds to antidepressants which
interfere with the reuptake of serotonin and
norepinephrine which increases their availability
to inhibit noxious stimuli.
Pathophysiology of visceral pain
Visceral pain:
Types - angina pectoris, myocardial infarction,
acute pancreatitis, cephalic pain, prostatic pain,
nephro-lytiase pain.
Receptors: unmyelinated C – fibres
For human pathophysiology the kinds of stimuli apt
to induce pain in the viscera are important.
It is well-known that the stimuli likely to induce
cutaneous pain are not algogenic in the viscera.
This explains why in the past the viscera were
considered to be insensitive to pain.
Pathophysiology of visceral pain
Visceral pain stimuli:
•abnormal distention and contraction of the hollow
viscera muscle walls
•rapid stretching of the capsule of such solid visceral
organs as are the liver, spleen, pancreas.
•abrupt anoxemia of visceral muscles
•formation and accumulation noxious substances
•direct action of chemical stimuli (oesophagus, stomach),
•traction or compression of ligaments and vessels
•inflammatory processes
•necrosis of some structures (myocardium, pancreas)
Pathophysiology of visceral pain
Mechanisms involved in referred pain:
convergence of impulses from viscera and from
the skin in the CNS:
- sensory impulses from the viscera create an
irritable focus in the segment at which they
enter the spinal cord.
- afferent impulses from the skin entering the
same segment are thereby facilitated, giving
rise to true cutaneous pain.
senzitization of neurons in dorsal horn
Pathophysiology of visceral pain

Painful visceral afferent impulses activate anterior
horn motor cells to produce rigidity of the muscle
(visceromotor reflexes)
 A similar activation of anterolateral autonomic cells
induces pyloerection, vasoconstriction, and
other sympathetic phenomena
 These mechanisms, which in modern terms can be
defined as positive sympathetic and motor feedback
loops, are fundamental in refered pain
 It is clear that painful stimulation of visceral
structures evokes a visceromuscular reflex, so
that some muscles contract and become a new
source of pain
Referred visceral pain
Clinical aspects
 Intricate conditions - in some types of pain, e.g.
chest pain, is difficult to distinguish the true cause
of pain because such kind of pain may be related to
cervical
osteoarthrosis, esophageal hernia, or
cholecystitis.
 It is difficult to ascertain whether these intricate
conditions are due to a simple addition of impulses
from different sources in the CNS or to somatovisceral
and viscerosomatic reflex mechanisms.
Clinical aspects
 It has been demonstrated that the modulation
process is facilitated if the experience to be retained
is repeated many times or is accompanied by pleasant
or unpleasant emotions.
Pain is, at least in part, a learned experience - e.g.
during the first renal colic, true parietal pain followed
visceral pain after a variable interval.
 In subsequent episodes of renal colic pain, parietal
pain developed promptly and was not preceded by
true visceral pain.
This is probably due to the activation of central
modulation.
EVALUATION
OF
PAIN
EXPERIMENTAL
EVALUATION
OF
PAIN
Somatic pain models
Hot plate test
Tail flick test
Tail immersion test
Analgezimeter test
Visceral pain models
Writhing test
Capsaicin colon stimulation test
Inflammatory cystitis test
(clyclophosphamide)
Behavioural models
Activity cage test
Hole board test
Inflammation models
Pletismometer test
Subcutaneous pellets implantation
!!! The results obtained
in experiments can not
be directly extrapolated
in humans



CLINICAL
EVALUATION
OF
PAIN
Pain history
Description: severity, quality, location,
temporal features, frequency, aggravating &
alleviating factors
Previous history
Context: social, cultural, emotional, spiritual
factors
Meaning
Interventions: what has been tried?
Physical exam in pain assessment
Inspection / Observation
• facial expression: grimacing; appears anxious; flat
affect
• body position and spontaneous movement: there may
be positioning to protect painful areas, limited
movement due to pain
• diaphoresis – can be caused by pain
• areas of redness, swelling
• atrophied muscles
Physical exam in pain assessment
Palpation
• localized tenderness to pressure or
percussion
• fullness / mass
• induration / warmth
Physical exam in pain assessment
neurological examination
Important in evaluating pain, due to the possibility of spinal
cord compression, and nerve root or peripheral nerve lesions
Sensory examination
• Areas of numbness / decreased sensation
• Areas of increased sensitivity, such as allodynia or
hyperalgesia
Motor (strength) exam
Deep tendon reflexes – intensity, symmetry
• Hyperreflexia and clonus: possible upper motor neuron
lesion, such as spinal cord compression or cerebral
metastases.
• Hyoporeflexia - possible lower motor neuron impairment.
Assessing pain intensity
• Use a numeric pain rating scale in most
clinical settings.
• The most common is an 11 point scale
where 0 = no pain and 10 =worst pain
imaginable.
• Many use a 0 to 5 faces scale for children.
Assessing pain intensity
Assessing pain intensity
in children
Assessing pain intensity
Diagnosis
• Medical diagnoses related to the pain: underlying diagnoses causing
pain
• Pain type (acute, neuropathic, visceral, etc.), intensity, impact on
quality of life and function
• Medical comorbidities contributing to pain and/or affecting
treatment: cardiovascular, cerebrovascular or neuromuscular diseases
• Medications that may interfere with the usual choices of drug or
nondrug treatments.
• Psychosocial issues and patient's ability to cope with pain
Factors that impact treatment planning and may affect response to
treatment include depression, anxiety, negative emotions, past
experiences, illness perception, alcohol dependence, substance abuse
and current social situations.
Clinical aspects
• Pain cannot be treated on the basis of
pain intensity alone, for example with
numeric based drug treatment algorithms
like those commonly used for blood sugar
or blood pressure.
• Rather, clinicians must respond to pain
reports in a manner appropriate to the type
of pain (e.g., acute versus chronic;
neuropathic versus inflammatory) and
setting (e.g., inpatient versus outpatient).
THANK YOU !