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Activity of Murine Raphe Magnus Cells Predicts Tachypnea and On-Going Nociceptive Responsiveness

¹Department of Neurobiology and ²Committee on Neurobiology, University of Chicago, Chicago, Illinois

Submitted 13 August 2007; accepted in final form 2 October 2007

In rats, opioids produce analgesia in large part by their effects on two cell populations in the medullary raphe magnus (RM). To extend our mechanistic understanding of opioid analgesia to the genetically tractable mouse, we characterized behavioral reactions and RM neural responses to opioid administration. d-Ala², N-Me-Phe⁴-Gly⁵ol-enkephalin, a mu-opioid receptor agonist, microinjected into the murine RM produced cardiorespiratory depression and reduced slow wave electroencephalographic activity as well as increased the noxious heat-evoked withdrawal latencies. As in rat, RM cell types that were excited and inhibited by noxious stimuli, termed ON and OFF cells, respectively, were observed in mice. However, in contrast to findings in rat, opioid doses that suppressed withdrawals did not alter the background discharge rate of murine ON and OFF cells, suggesting that the cellular mechanisms by which the murine RM generates opioid analgesia are substantially different from those in rats. Murine ON cell discharge did not predict the latency or magnitude of an ensuing withdrawal but did correlate to the magnitude and latency of concurrent withdrawals. Although opioids failed to alter the background discharge of ON and OFF cells, they reduced the responses of RM neurons to noxious stimulation, further evidence that RM modulates on-going withdrawals. In characterizing the role of RM in respiratory modulation, we found that ON cells burst and OFF cells paused during tachypneic events. The effects of opioids in the murine RM on homeostasis and the association of ON and OFF cell discharge with tachypnea corroborate roles for opioid signaling in RM beyond analgesia.

This article has been cited by other articles:

				K. M. Hellman, S. J. Mendelson, M. A. Mendez-Duarte, J. L. Russell, and P. Mason Opioid microinjection into raphe magnus modulates cardiorespiratory function in mice and rats Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2009; 297(5): R1400 - R1408. [Abstract] [Full Text] [PDF]