What is nociception?
The sensory process that provides the signals that trigger pain.
Transduction of nociceptive stimuli occurs in the free nerve endings of unmyelinated ‘C’ fibres & thinly myelinated ‘Ad’ fibres
4 important points on types of sensory afferents?
1) Large diameter, rapidly conducting afferents (I/II) associated with low threshold mechanoreceptors
2) Small diameter, slow conducting afferents (III/IV) associated with nociceptors & thermoceptors
3) Thermal & mechanical nociceptors have Adelta fibres
4) Polymodal nociceptors have C fibres
Features of 1st pain?
Fast A-delta fibres Sharp or prickling Easily localised Occurs rapidly Short duration Mechanical or thermal nociceptors
Features of 2nd pain?
Slow C-fibres Dull ache, burning Poorly localised Slow onset Persistent Polymodal nociceptors
Where do nociceptive fibres have their cell bodies? What happens after they enter the dorsal horn?
Within the dorsal root ganglion.
After terminals enter the dorsal horn, they travel up/down a short distance (1 or 2 spinal segments) within the Zone of Lissauer. Afferent terminals then synapse within the superficial laminae of the dorsal horn.
They synapse with neurons in lamina I & II (substantia gelatinosa)
Referred pain of:
a) Bladder
b) Ureter
c) Prostate
d) Appendicitis
a) Perineum
b) Lower abdomen & back
c) Lower trunk & legs
d) Navel wall area
What excitatory neurotransmitter do pain afferents release?
Glutamate
What important neuropeptide do synaptic terminals have?
Substance P. (most dense in superficial dorsal horn)
WHO analgesic ladder?
- ->Aspirin, NSAIDS, Cox-2 inhibitors
- ->Codein, Tramadol
- ->Morphine, Fentanyl, Methadone
Mechanism of action of non-opioid analgesics? (NSAIDS/ COX-2 inhibitors)
Act mainly peripherally (paracetamol has central activity)
Mechanism of action of opioid analgesics? (tramadol, codeine, morphine)
Act at 2 sites in the spinal cord:
Presynaptically pain signal transmission is reduced.
Postsynaptic membrane is hyperpolarised, decreasing the probability of action potential generation.
-Main eficacy in nociceptive pain.
What pain relief would you use in Renal failure?
NOT morphine/codeine.
Use fentanyl or oxycodone
What are the features of neuropathic pain?
Often persistent or recurrent
Associated with sever comorbidity & poor quality of life
(MECHANISM: trauma/amputation etc leads to hyperexcitable spinal cord which leads to expanded hyperexcitable dorsal horn with new inputs)
How are Antidepressants (TCAs) used in neuropathic pain therapy?
Inhibition of neuronal reuptake of noradrenaline & serotonin.
Types of Anticonvulsants used in neuropathic pain therapy?
Gabapentin, Pregabalin, Carbamazepine
What is used to measure pain quality?
McGill Questionaire