Pain: Underlying Mechanisms, Rationale for Assessment

Jessie VanSwearingen

, Ph.D, PT Associate Professor Department of Physical Therapy University of Pittsburgh School of Health and Rehabilitation Sciences

PAIN “…an unpleasant sensory and emotional experience….primarily associate with tissue damage or describe in terms of such damage or both.” Intl. Assoc. for Study of Pain

The Report of Pain 3 components of the patients experience: – sensory discriminative (localize, quality) – motivational / affective (emotional) – cognitive / evaluative (meaning)

The Report of Pain Relation of pain and tissue damage: not consistent or constant ‘All pain is truly experienced’ (- a helpful clinician belief…)

Terminology of Pain

Nocioception

neural response related to potentially tissue damaging stimuli

Pain

conscious experience of nocioception

Terminology of Pain

Experience of pain

• dysthesia - experience abnormal noxious sensation – paraesthesia - abnormal nonpainful sensation; – hyperpathia- exaggerated pain response to noxious or nonoxious stimuli) • allodynia - perception of nonoxious stimuli as painful

Terminology of Pain • hyperalgesia increased pain response to painful stimuli • hypoalgesia - decreased sensitivity to noxious stimuli • hyperesthesia and hypoesthesia increase or decrease, respectively, in sensitivity to nonnoxious stimuli

Characteristics of Pain Nocioceptive pain - directly related to the activation of peripheral nocioceptors somatic - aching , squeezing, stabbing visceral - cramping, knawing, rise and fall

Characteristics of Pain • Neuropathic - pain assumed to be related to aberrant sensory processing (PNS or CNS) • Deafferentation- sympathetic maintained alterations in peripheral transmission or central representation ‘burning, lancinating, electrical’

Characteristics of Pain • Idiopathic - pain persisting without identifiable organic basis or excessive pain for organic processes (presumes some clinical correlation) (psychogenic - no clinical observations correlating with the pain)

Nocioceptive Pain

Activation of nocioceptors by tissue-damaging stimuli. Mechanisms:

• neurogenic inflammation - vasodilation; inflammatory cells; antidromic (polymodal) nocioceptor release of Substance P and others from nerve terminals • endogenous substances - directly activate nocioceptors - histamine, Subs. P, bradykinin, ACH, serotonin, K+ • prostoglandins - sensitize nocioceptors: produce lower thresholds for noxious stimuli (also: serotonin, ADP, NE, interleukin, NGF); role in development of chronic pain

Neuropathic Pain Peripheral tissue injury leading to aberrant somatosensory processing  pathophysiologic changes, which sustain a pain experience.

Mechanisms: – peripheral generators – sympathetic maintained – central (mechanism) generators

Neuropathic Pain Example: Axonal Injury 1) multiple axon sprouts  neuroma 2) axon sprouts  spontaneous activity (peripheral generator)

pain

3) neuromas sensitive chemical sensitivity “tenderness” mechanical and

chronic pain

4) ephases - spread of impulses in juxtaposed nerve fibers; incl sympathetic nerves (sympathetic maintained) 5) ectopic generation of impulses in DRG,  transmitter release  dorsal horn neurons expand receptive fields (hyperalgesa)

Neuropathic Pain:CNS Activity • Increased activity in spinal cord, thalamus, cortex following peripheral nerve injury: – central sensitization of neurons – abnormal feedback (sympathetic outflow  stimulate peripheral nocioceptors)

Clinical Events of Pain Hyperalgesia –1º -site of injury: peripheral nocioceptor sensitization –2 º -surrounding region: peripheral and central mechanisms –central - hyperexcitable neruon activated by nocioceptor

Pain episodes with the same phenomena may not have the same mechanism

Referred Pain

Phenomena:

• stimulation of peripheral nerve fascicles, report of pain throughout the extremity • pain from muscle or visceral injury accompanied by cutaneous hyperalgesia

convergence-projection theory

• convergent input of nocioceptors from different sources on to the same projection neurons or central neurons

Basis for Joint and Bone Pain: Joint Nocioceptors 1. nocioceptors - polymodal cutaneous receptor; c-fiber, unmyelinated (capsule, type IV) 2. free- nerve endings - A -delta nocioceptors in int’l and ext’l joint ligaments 3. Synovium - small diameter, neuropeptide containing fibers A-delta and C-fibers innervate joint nocioceptors; ? Also sensitive mechanical and chemical stimuli

Basis for Joint and Bone Pain: Joint Mechanoreceptors 1. Large diameter, fast-conducting afferents, serving…..

2. Corpuscular receptors - low-threshold, dynamic receptors; capsule outer layer type I, subsynovial layer - type II, dynamic receptors on surface of joint ligaments 3. Mechanically Insensitive Afferents (MIAs) - C-fiber afferents, become sensitive to mechanical stimuli only with inflamed joint

Basis for Joint and Bone Pain: “Sleeping Nocioceptors” (MIAs) • insensitive to pain or mechanical stimuli • become spontaneously active • active during non-noxious movement • enlarged receptive fields • (central targets unknown)

Basis for Joint and Bone Pain: Spinal Cord Mechanisms Dorsal horn neurons: nocioceptive specific (NS) wide dynamic range (WDR) articular inputs visceral Cutaneous muscle afferents afferents Basis for arthritic pain being: •poorly localized •poorly discriminated Basis for: referred pain and hyperalgesia

Basis for Joint and Bone Pain: Spinal Cord Mechanisms Noxious joint inputs reach cortical targets.

– inputs from inflamed joints appear to take paths to widespread supraspinal targets With persistent nocioceptive input, dorsal horn neurons  in sensitivity – enhanced responsiveness – enlarged receptive fields

Basis for Joint and Bone Pain: Spinal Cord Mechanisms With acute joint inflammation,

(sensitivity)

1) dorsal horn neurons with little response to movement show large response (

enhanced receptive fields

) 2) respond to stimuli remote from the site of inflammation 3) become spontaneously active

Basis for Joint and Bone Pain: Somatosensory Cortex Chronic inflammation

receptive field changes

• increased ‘background activity’ • prolonged response to non-noxious stimuli (reduced inhibition of pain afferents in the dorsal horn - decreased descending inhibitory pain projections with

inflammation)

Neurogenic Inflammation Example: “axon reflex” - localized vasodilation and exudation in response to an irritant - intact sensory innervation - mediated by release of neuropeptides from C-fiber terminals  change in vascular tone and permeability production of inflammatory cells; immune response

Neurogenic Inflammation • Partially attenuated by Substance P depleter (eg

capsaicin)

• In Rheumatoid Arthritis, reduced neuropeptide Y (vasoconstrictor) in the sympathetic nerve terminals  no ‘stop’ to the inflammatory response

Summary of Pathophysiology of Joint and Bone Pain Chemical Nocioception • pain activation of nocioceptors • primary hyperalgesia - sensitization of nocioceptors • swelling, vascular response to neuropeptide release

Summary of Pathophysiology of Joint and Bone Pain Mechanical Nocioception – (joint bomechanics) “mechanical nocioceptors activated – primary hyperalgesia, sensitized mechano - nocioceptors – mechanoreceptors, incl remote musculotendinous site receptors, induce dorsal horn plasticity

Summary of Pathophysiology of Joint and Bone Pain Secondary Hyperalgesia / Neuropathic Model • altered central pathways with chronic arthritis (both altered dorsal horn neurons responding and the pattern of the response) – changes in threshold for response – changes in projection targets – changes in the responsiveness • referred pain to: other joints; cutaneous areas and deeper tissues

Clinical Assessment of Joint and Bone Pain Looking for: • anatomic origin - define the tissue damage • mechanisms of pain production • associated disease

Clinical Assessment of Joint and Bone Pain Finding a hyperalgesic joint in the region of pain - likely to be the origin - other signs: crepitus, swelling (implies nocioceptors activated) but in osteoarthritis: mechanoreceptors could elicit mechanical nocioception and sensitize primary afferents…..

Joints which don’t move and joints that move properly can be painful

.

Clinical Assessment of Joint and Bone Pain Recognizing Bone pain: (causes: vascular, infection, neoplastic, metabolic) • not influenced by posture or movement • worse at night • well localized, over the painful site (eg vertebra) (eg. Osteonecrosis; osteoporotic fracture)

Review this lecture