Pain

Question 0

Nociceptive pain

Answer 0

Stimuli:
Mechano -> free nerve endings
Chemo
- metabolites - K+, ATP, pH
- neurotrans - substance P, NE
- tissue products - histamine, bradykinin, nerve GF
- inflammatory - prostaglandins, leukotrienes, cytokines

Can act

• directly
• via modification/sensitization
• ex: PGE, bradykinin, NGF -> G protein -> PKA, PKC -> TRPV1
• causing release of other stimuli

Question 1

Pain definitions

Answer 1

Allodynia - pain from non-painful stimulus (tapping)
Hyperalgesia - increased pain from painful (pin)
Hyperesthesia - increased sensation of any sort
Dysesthesia - wierd sensation (pins, needles)

Neuropathic - from nervous, usu sharp, stabbing
Nociceptive - tissue damage, nociceptors

Question 2

Pain nerve fibers

Answer 2

Slowly adapting
Relatively slowly conducting
- A-delta (myelin) - 15 m/s, C (unmyelin) < 1 m/s
Release neurotransmitters at both ends
Peripheral -> sub P, neurokinin A, CGRP -> inflammation
- neurotrophic (BDNF) -> remodelling
Central -> zone of Lissauer -> poorly localized

Question 3

Pain pathways

Answer 3

Peripheral fibers -> dorsal horn synapse (substantia gelatinosa)

• C fibers (slow)
  
  • > layer I - marginal/specific cells - localized, sharp, stinging
  • > layer IV, V - wide dynamic range - intensity, burning, aching
  • poorly localized (convergent input)
  • most viscera only through this pathway -> poorly localized

Neospinothalamic: marginal and wide dynamic range -> ventral commissure -> anterolateral tract -> VPL -> somatic cortex
Paleospinothalamic: wide dynamic range -> reticular thalamic nuclei -> broad cortex -> mood (also brainstem autonomic)

Question 4

Localization of pain

Answer 4

Generally poor due to convergent fibers
Viscera - only through convergent pathway
Trigeminal - synapse convergent with cervical, etc
- location is less diagnostic than provoke/palliate, associated sx

Question 5

Pain inhibitory pathways

Answer 5

A-beta - touch, pressure, proprioception (rubbing toe)
-> inhibitory interneurons in dorsal horn
C fibers -> enkephalinergic interneurons -> opiate receptors
- temporary inhibition after initial stimulus
Descending: periaqueductal gray -> medulla -> interneurons
- raphe -> serotonin, lateral medulla -> NE
- all levels have enkephalinergic and opiate receptors

Question 6

Pain control strategies

Answer 6

Opiates - activate suppression, directly inhibit -> dependency
Serotonin or NE - esp good for chronic or neuropathic
Ca and Na channels - gabapentin, etc

Question 7

Central pain syndromes

Answer 7

Lesion, chronic -> deafferentation -> loss of inhibitory/GABA
Severe pain, difficult to treat

ex: thalamic pain syndrome

Question 8

Cortical pain effects

Answer 8

Similar to depression!

• inc ant cingulate, medial frontal (interpretation, reaction)
• thalamus -> attention
• dec post cingulate

Question 9

Facilitation

Answer 9

Similar mechanisms to hippocampal memory

• short term adaptation - PKA
• long-term potentiation
  
  • partial depolarization + NMDA -> Ca -> changes in sensitivity
  • also neurotrophic release (BDNF -> tyrosine kinase TRP)
  • from both glial cells and activated pain axons