Harada_2000_Neurosci.Lett_284_163

Several lines of evidence suggest that central cholinergic neurons play a key role in the perception and control of pain. We investigated the effects of analgesics on the increase in central cholinergic activity and writhing responses elicited by i.p. injection of acetic acid. ACh efflux from the rat cerebral cortex and hippocampus was measured in the absence of a cholinesterase inhibitor using an in vivo microdialysis technique and a highly sensitive and specific radioimmunoassay. ACh efflux from the cerebral cortex was significantly increased during the first 30 min after acetic acid injection and then returned to the control levels. In contrast, acetic acid-induced writhing responses, indicative of the perception of pain, persisted for almost the entire 120 min observation period. No changes in ACh efflux were observed in the hippocampus. The centrally-acting analgesic morphine and the peripherally-acting analgesic indomethacin each completely abolished the enhanced cerebral cortical ACh efflux and the writhing, whereas diazepam, a muscle relaxant, selectively suppressed only the writhing. These results demonstrate that peripheral nociceptive stimulation transiently increases cholinergic activity in the cerebral cortex, but not in the hippocampus, and that analgesics suppress both the enhanced ACh efflux and the writhing induced by acetic acid.