How is pain perceived?

Sanjay Manohar (Oxford 2015)

Pain pathways

------------- Definition; Roles of pain in behaviour Adaptive function. Phylogenetically old. "Anterolateral system" 1. Receptors = free nerve endings, polymodal but some specificity - mechanoreceptors - channels - thermoreceptors - channels (Thermal grill illusion) - chemoreceptors (itch) - damage / stress - acid release -- TRP receptor channels 2. Fibres. cell body in DRG. glutamatergic. Adelta C ------------------------------------------- light myelination unmyelinated 5um <2um up to 15 m/s <2 m/s sharp ache localised diffuse complete adaptation slow adapting more modality specific more polymodal Anoxia experiment local anaesthetics (lignocaine, VGNaC) 3. Spinal cord lamina I/V -> lissauer tract (2 segments) substantia gelatinosa lamina II decussation, lateral and ventral spinothalamic tract Brown-Sequard. Diagram. 4. VPL/VPM -> S1 postcentral gyrus Plus: Trigeminothalamic (V) Spinohypothalamic - hormonal and autonomic-visceral responses Spinoreticular tract -> reticular formation -> cortex: arousal

Factors influencing

Referred pain - larger RFs; convergence? Subjective intensity is variable Potentiation by damage, sensitisation by chronic pain - hyperalgesia, allodynia, neuropathic pain prostaglandin, bradykinin, Nociceptin (NSAIDs) Substance P (a tachykinin) = signals cell damage, potentiates afferent, also central cotransmitter. Top down control - Gelatinosa & Periaqueductal grey: mu and kappa opioid receptors (DBS) dynorphins, enkephalins, endorphins: natural neurotransmitter peptides (->opiate drugs); G-protein coupled - modulate transmission. Tachyphylaxis, addiction Manipulate expectation socially/visually; hypnosis, placebo Bottom up control Melzack and Wall 1960s gate theory: Abeta tactile -> inhbitory interneuron. TENS Effect: reflex withdrawal, arousal, perception, learning.

Big picture:

compare the injured war hero with the chronic pain sufferer adaptive vs maladaptive pain scale! arguably the humanity's biggest problem?