Download Pain Classification: Nociceptive, Neuropathic, Central and Mixed

Pain Classification:
Nociceptive, Neuropathic, Central and Mixed
Rachael Rzasa Lynn, MD
Chronic Pain Zoom Webinar
2 December 2015
Definitions
• Most basic = neurophysiologic classification
– based on presumed mechanism of pain.
• Simplified, there are 2 types of pain:
– nociceptive pain
– non-nociceptive pain
• Neuropathic pain
• Idiopathic pain
– ≠psychogenic pain!
Nociceptive Pain
• Pain due to continuous tissue
injury
– actual or threatened damage to
non-neural tissue results in
activation of peripheral
nociceptors
• noxious stimulus 
electrochemical impulses in
peripheral nerves  spinal cord
 brain
= transduction, transmission,
modulation, and perception
– Examples: arthritis pain, acute
post-traumatic pain
– Subdivided into
somatic pain and visceral pain
Basbaum et al. Cell 2009; 139: 267-284
Nociceptive Pain
• Somatic pain
– excitation and/or sensitization of nociceptors in
tissues such as bone, periarticular soft tissue,
joints, and muscles
• Well localized
• Intermittent or constant
• “aching,” “stabbing,” “gnawing,” “throbbing”
Nociceptive Pain
• Visceral pain
– Not produced by all visceral organs
• Liver, kidney, most solid viscera, and lung parenchyma are not
sensitive to pain.
– Not always created by visceral injury
– Cutting intestine causes no pain, stretching of the bladder is painful
– Diffuse and poorly localized
• No separate visceral sensory pathway and low proportion of
afferent nerve fibers from viscera
• Intermittent or constant
• “dull,” “colicky,” “squeezing”
– Referrs to other locations.
– Accompanied by motor and autonomic reflexes
• Eg, nausea, vomiting, muscle tension, etc.
Neuropathic Pain
• “Pain arising as a direct consequence of a lesion or disease affecting
the somatosensory system.”
– at any point(s) within the somatosensory pathways
– Pain from lesion/disease sustained by aberrant processing in the
peripheral and/or central nervous system
– typically described as “sharp” or “burning”
• This is a clinical description (NOT a diagnosis)
– According to IASP,
• “this requires a demonstrable lesion or a disease that satisfies established
neurological diagnostic criteria.”
• “The presence of symptoms or signs (e.g., touch-evoked pain) alone does not
justify the use of the term neuropathic.”
• “It is common…that diagnostic testing may yield inconclusive or even
inconsistent data. In such instances, clinical judgment is required to reduce the
totality of findings in a patient into one putative diagnosis or concise group of
diagnoses.”
Neuropathic Pain
• Subsets
– Peripherally generated pain:
• involves such cervical or lumbar radiculopathy, spinal nerve
lesions, and brachial or lumbosacral plexopathies
– Centrally generated pain:
• involves injury to the central nervous system at the level of
the spinal cord or above.
– Sympathetically maintained pain:
• may be generated peripherally or centrally
• characterized by localized autonomic dysregulation
– vasomotor or sudomotor changes, edema, sweating, trophic
changes including atrophy
– Complex Regional Pain Syndrome
Central Pain States
• Central pain: Pain initiated or caused by a primary
lesion or dysfunction in the central nervous system.
– Can be produced by an type of vascular, demyelinating,
infectious, inflammatory, or traumatic lesion in the brain
or spinal cord
• Eg, post-stroke pain
• Central sensitization: Increase in the excitability of
neurons in the spinal cord.
– Increased responsiveness of nociceptive neurons in the
central nervous system
• Increased response to input to which they normally respond
• Activation in response to subthreshold input
IASP Pain Classification
• Multidimensional Classification of Pain
– Developed to standardize descriptions of pain syndromes and provide a point
of reference
– Uses 5 axes to classify chronic pain
• Region of the body affected (Axis I),
• System whose abnormal functioning could produce the pain (Axis II),
• Temporal characteristics of pain and pattern of occurrence (Axis III),
• Patient's statement of intensity and time since onset of pain (Axis IV)
– Mild, medium or severe, each for ≤1 month, 1-6 months or >6 months
duration
• Presumed Etiology (Axis V)
– Infection, inflammation, neoplasm, toxic, metabolic, etc
• Uses the above to create 5-digit code assigned to each chronic pain
diagnosis
• Limitations: Does not include psychosocial or behavioral data
– ALL PAIN HAS A PSYCHOLOGICAL COMPONENT
Proposed Taxonomy of Pain Based
upon Multifactorial Assessment
• Pain Parameters:
– Anatomy/System
– Duration/Intensity/Quality
– Associated Abnormality (physical/psychological)
• Underlying Diseases:
– Signs/Symptoms
• Pain Mechanisms:
– NEUROPHYSIOLOGICAL
• Primary afferent involvement
• CNS involvement
– PSYCHOLOGICAL
• Cognitive-Affective-Behavioral Involvement
–
–
–
–
Cognitive appraisal of pain
Coping
Affect/mood
Environment
Mixed Pain
• Most pain is mixed
• Even “nociceptive pain” can lead to central
sensitization
– Eg, osteoarthritis
• fMRI and PET changes
– Increased activation in brain areas involved with affect, aversive
conditioning and motivation than experimental pain
• These patients display hyperalgesia locally and in areas
distant from the arthritic joint
– After THA, these patients display reduced pain in both areas
• ALL pain has a psychological component!
Aranda-Villalobos P et al. Arthritis & Rheumatism 2013; 65: 1262-1270.
Sofat et al. Rheumatology 2011; 50: 2157-2165
REV I EW S
b
c
Brain
S1
Dorsal root
ganglion
Unmyelinated
C- bres
Lightly myelinated
Aδ- bres
Heavily myelinated
Aδ- bres
ACC
PFC
IC
Thalamus
Cortex
CeA
Dorsal
PAG
Midbrain
LC
Pons
RVM
Medulla
Ventral
Spinal cord
Second-order pain
projection neurons
Spinal sites
a
Peripheral terminal
Noxious stimuli
Thermal
Mechanical
Chemical
In ammation
Tissue damage
Peripheral tissue
Ion
channels
TRPA
TRPM
TRPV
Nav
KCNK
ASICs
First-order
neuron
Normal,
physiological pain
TRP: Transient receptor potential channel (many
subtypes)
TRPA1=cold (<15°C) in injury (not normal,
acute cold), menthol
TRPM8=cold(<25°C), menthol
TRPV1=heat (>43°C), capsaicin
ASICs: Acid-sensing ion channels
KCNK: Potassium channel subtypes
Nav: Voltage-gated sodium channel isoforms
Also Voltage-gated Calcium channels (N- and T-type);
α2δ subunit ↑’d after injury
Mechanical transduction may occur via TRP, ASIC
KCNK channels
Figure 1 | Physiological pain processing. a | Nociceptive signals areand/or
transmitted
from the periphery by nociceptive
Nature Reviews | Immunology
Grace PM, et al. Nat Rev Immunol. 2014; 14: 217-231
sensory neurons (first-order primary afferent neurons) the peripheral terminals of which are clustered with ion
Basbaum et al. Cell 2009; 139: 267-284
Mechanistic Stratification of Medications Used
to Treat Neuropathic Pain
Fig. 4. Mechanistic stratification of antineuralgic agents. PNS = peripheral nervous system; CBZ = carbamazepine; OXC =
oxcarbazepine; PHT = phenytoin; TPM = topiramate; LTG = lamotrigine; TCA = tricyclic antidepressant; NE =
norepinephrine; SSRI = selective serotonin re-uptake inhibitor; SNRI = serotonin and norepinephrine re-uptake inhibitor; GBP
= gabapentin; LVT = levetiracetam; NMDA = N-methyl-D-aspartate; NSAID = nonsteroidal anti-inflammatory drug.
Beydouna & Backonja M. J Pain Symptom Manage. 2003;25:S18-30