Nociception brain sites

The best-understood sites of action of morphine are at spinal and brainstem/ midbrain loci, producing both the wanted and unwanted effects of the opioid. The spinal actions of opioids and their mechanisms of analgesia involve (1) reduced transmitter release from nociceptive C-fibres so that spinal neurons are less excited by incoming painful messages, and (2) postsynaptic inhibitions of neurons conveying information from the spinal cord to the brain. This dual action of opioids can result in a... 

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The 5-HT3 receptor is the only monoamine neurotransmitter receptor that functions as a lig-and-gated ion channel, controlling the flux of Na-i- and K+ ions. 5-HT3 receptors are located on parasympathetic nerve terminals in the gastrointestinal tract, and high densities are found in areas of the brain associated with the emetic response, such as the area postrema. The antiemetic effects of 5-HT3 antagonists, such as ondansetron, result from actions at these sites. 5-HT3 receptors in the dorsal horn of the spinal cord have been implicated in nociception and development of new 5-HT3 receptor-related compounds may have potential as non-opioid, non-addictive analgesics. 

Lutfy, K. and Weber, E. Attenuation of nociceptive responses by ACEA-1021, a competitive NMDA receptor/glycine site antagonist, in the mice, Brain Res. 1996, 743, 17-23. 

Another important site of opioid-mediated analgesia is the periaqueductal gray matter. This area of brain, as noted above, is rich in opioid receptors, and exercises descending anti-nociceptive influence on the dorsal horn of the spinal cord. 

EinaUy, prostanoids act both at the peripheral sensory neurons and at central sites within the spinal cord and brain to evoke hyperalgesia (Ito et al., 2(X)1). Recent data support the involvement of PGI and PGE in pain although these prostanoids do not cause pain directly, they have been shown to potentiate the nociceptive responses induced by bradykinin and histamine (Parente and Perretti, 2(X)3). 

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