PHARMACOLOGY Pain and Breathing

The pre-Boetzinger complex (PBC) is a region in the lower brainstem that generates and controls spontaneous breathing movements. Manzke et al. used immunocytochemistry and single-cell polymerase chain reaction analysis to show that serotonin 4A [5-HT_4A] receptors are expressed in respiratory neurons in the PBC. Application of a 5-HT_4A receptor agonist reduced the respiratory depression evoked by the opioid agonist fentanyl without the loss of its analgesic effect. This effect could be explained by the antagonistic interaction of the two different receptor systems converging on the same intracellular signaling pathway. The absence of 5-HT_4A receptors in dorsal horn neurons in the spinal cord explains why fentanyl still acts as a pain reliever under these conditions.

T. Manzke, U. Guenther, E. G. Ponimaskin, M. Haller, M. Dutschmann, S. Schwarzacher, D. W. Richter, 5-HT_4(a) receptors avert opioid-induced breathing depression without loss of analgesia. Science 301, 226-229 (2003). [Abstract] [Full Text]

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5-HT_4(a) Receptors Avert Opioid-Induced Breathing Depression Without Loss of Analgesia

Till Manzke, Ulf Guenther, Evgeni G. Ponimaskin, Miriam Haller, Mathias Dutschmann, Stephan Schwarzacher, and Diethelm W. Richter (11 July 2003)
Science 301 (5630), 226. [DOI: 10.1126/science.1084674]
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