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?