Nociception Flashcards
Adelta fibre diameter:
1-5um.
Adelta fibre CV:
3-30m/s.
C fibre diameter:
0.2-1.5um.
C fibre CV:
0.5-2m/s.
Abeta fibre diameter:
6-12um.
Abeta fibre CV:
33-75 m/s.
Membrane of nociceptors contain receptors that …
Covert energy of noxious stimuli into depolarising electrical potential.
What ion channel mediates pain producing action of capsaicin, and is activated by temperatures over 45C?
TRPV1.
What is the menthol-responsive and cold-sensing channel?
TRPM8.
What does congenital pain insensitivity show about the role of other ion channels (v-g sodium channels) in nociception?
Caused by loss of function mutation in SCN9A gene encoding NaV1.7 v-g Na+ channel.
Mutations in SCN9A gene can also cause what? Implicated in what condition?
Hyperexcitability of nociceptors. Inherited erythromelalgia, ongoing burning pain of extremities.
Role of v-g Na+ channels also highlighted by what pharmacological evidence?
Local anaesthetics, lidocaine, blocks v-g Na+ in primary afferent fibre.
What mechanism highlights the role of inflammation in pain sensitivity?
TRPv1-mediated membrane currents are enhanced by a reduction in pH, characteristic of the chemical milieu of inflammation.
Describe the spinothalamic tract:
Sensory neurons synapse in dorsal root ganglion, second order neurons decussate and ascend in anterolateral white matter to the VPL. Then somatosensory cortex.
Describe the spinoreticular tract:
Fibres decussate after DRG and ascend the contralateral cord to reach the brainstem reticular formation, before projecting to the thalamus and hypothalamus.
Describe the spinomesencephallic tract:
DRG, decussate, travel upwards in anterolateral column to midbrain, terminating in PAG and superior colliculus.
Role of the spinothalamic tract:
Localisation.
Role of the spinoreticular tract:
Arousal and emotional responses to pain.
Role of the spinomesencephalic tract:
Modulates pain by connections with the PAG.
What evidence is there that the VPL organises input from the spinothalamic tract according to body region, preserving spatial fidelity of signal to somatosensory areas?
Neurons in VPL have small RFs matching those of presynaptic spinal neurons .
What evidence is there that the thalamus plays a role in pain?
Electrical stimulation of thalamus leads to intense pain. And lesions can cause neuropathic pain condition Dejerine-Roussy syndrome. Causes spontaneous burning pain and abnormal sensations (dysesthesias).
Gate control theory suggests that pain arises from the …
Balance of activity in nociceptive and non-nociceptive afferent fibres.
What is the mechanism behind gate control theory?
Activation of non-n neurons engages inhibitory interneurons in the dorsal horn, closing a gate for the transmission of afferent signals. Activation of n neurons opens the gate.
Evidence for gate control theory?
Activation of low threshold afferent fibres can attenuate pain, TENS machine. Electrodes at peripheral locations can activate large diameter fibres innervating areas that overlap and surround area of pain.
What empirical observation may gate control theory explain?
Reflexive behaviour of shaking the hand after hammer blow or burn. May activate fibres that suppress pain transmission.
What shows that the PAG modulates pain?
Stim. produces analgesia. Also blocks spinally mediated withdrawal reflexes normally evoked by noxious stimuli.
How do PAG neurons modulate pain?
Make connections with neurons in rostroventral medulla, including serotonergic neurons in nucleus raphe magnus. Axons project through dorsal region of lateral funiculus to spinal cord, forming inhibitory connections.
What could a noadrenergic modulatory system originating in locus coeruleus explain?
Stress-induced analgesia.
What does morphine do?
Binds to brainstem opiate receptors, activates brainstem descending serotonergic pathway to spinal cord.
What shows that morphine acts by activating monaminergic systems?
Blocked if naloxone injected into PAG or NRM. Also bilateral transection of lateral funiculus blocks. This central analgesic actions involve activation of descending pathways.
What does C fibres having more mu receptors than Adelta fibres explain?
Why morphine is more effective at treating persistent> acute pain.
What is hyperalgesia vs allodynia?
Increased sensitivity to pain, perception of a tactile stimulus as painful.
Who showed that after prolonged stimulation, ‘silent’ fibres become responsive?
Raja, Campbell and Meyer (1984). Burnt areas on palm , mechanical threshold significantly decreased, and in an area larger than burn.
Why causes peripheral hyperalgesia ?
Activation of nociceptors releases substance P. Acts on mast cells in area which release histamine. Histamine directly excites C fibres.
Damaged tissue also releases prostaglandins which potentiate effects of histamine, lowering activation threshold of nerves for activation by it.
What highlights role of histamine in peripheral hyperalgesia?
NSAIDs are COX1 and COX2 inhibitors. They reduce prostaglandin synthesis.
When can central facilitation happen?
More signals to CNS, long term changes in activity at level of SC an brain. “Wind up”.
Mechanism behind central facilitation:
C fibres fire repeatedly, co-release of Glu and P. P enhances Glu-induced NMDAR activation by increasing response to glutamate. LTP.
What highlights role of NMDARs in central hyperalgesia?
Chronic pain can be treated with ketamine (Orhurhu et al., 2019).
Referred pain is what:
When pain spreads from visceral organs to distant site.
Referred pain, heart: , liver: .
Left arm, shoulder blades.
What causes referred pain:
Nociceptive axons from viscera enter spinal cord by same route as cutaneous axons. Convergence of information on same nocineurons.
Verbal-induced hyperalgesia is associated with what?
Increased adrencorticotropic hormone and cortisol plasma concentrations.
