Figure 4: Physiology of pain
Antinociceptive pathways are activated when pain signals in the spinothalamic tract reach the brain stem and thalamus. The periaqueductal gray matter and nucleus raphe magnus release endorphins and enkephalins. A series of physicochemical changes then produce inhibition of pain transmission in the spinal cord.
70% of endorphin and enkephalin receptors are in the presynaptic membrane of nociceptors. Thus, most of the pain signal is stopped before it reaches the dorsal horn. The signal is then further weakened by dynorphin activity in the spinal cord. The site of action of various analgesics is shown.
Dynorphin activation of alpha receptors on inhibitory interneurons causes the release of GABA. This causes hyperpolarisation of dorsal horn cells and inhibits further transmission of the pain signal.
Implications for pain therapy:
Medications that mimic the effects of endorphins and enkephalins are the mainstays of chronic pain therapy. Newer drugs that mimic or potentiate the effects of GABA or alpha-2 receptor agonists have made it possible to target therapy for chronic pain syndromes.