Pharmacological regulation of descending cortical control of the nociceptive processing

Clinical and experimental data indicate that the cerebral cortex plays an important role in pain perception and endogenous antinociceptive system function. Moreover, the enhancement of descending inhibitory cortical control may be involved in the mechanisms of analgetic effect of some agents. The present study was designed to investigate the effect of cortical electrical stimulation (as a model of descending inhibitory control) on the behavioral and electrophysiological signs of nociceptive response, decipher the mechanisms involved therein and evaluate the action of central analgesics (both opioid and non-opioid) on descending cortical control. In acute experiments in cats the inhibitory cortical influence on neuronal activity produced by nociceptive stimuli (electrical stimulation of tooth pulp, C-fibers of afferent somatic nerves, afferent cardiac structures) was most marked after stimulation of the first and second sensory and fronto-orbital areas. In chronic experiments on rats cortical stimulation reduced behavioral signs of visceral pain (writhing test) and also delayed the development of neuropathic pain syndrome along with lowering its intensity. Mu-opioid receptor agonists (morphine, fentanyl) potentiated the inhibitory cortical effect on the evoked neuronal activity. Pentazocine, which has pronounced kappa-receptor agonistic activity, was less effective. Naloxone eliminated the effects of both cortical stimulation and opioid analgesics. Serotonin receptor antagonist methysergide as well as p-chlorophenylalanine significantly decreased inhibitory cortical control and opioids effect. Monoamine re-uptake inhibitors with analgetic properties (imipramine, fluoxetine) potentiated the inhibitory effect of cortical stimulation. Adrenoceptor, dopamine, acetylcholine, GABA-receptor agents and antagonists of NMDA receptors had minor or no effect. Among non-narcotic analgesics, inhibitors of cyclooxygenase, metamysole and ketorolak increased only moderately the descending cortical control of nociception. Thus, the cerebral cortex is able to control the nociceptive processing in different pain syndromes (somatic, visceral or neuropathic pain). Opioidergic and serotonergic systems play the key role in this control. The effect over the cortical descending control is likely to be one of the components of the analgetic effect exerted by opioids and some other central analgesics.