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Tissue injury regulates serotonin 1D receptor expression: implications for the control of migraine and inflammatory pain.
J Neurosci. 2006 Aug 09; 26(32):8332-8.JN

Abstract

The anti-migraine action of "triptan" drugs involves the activation of serotonin subtype 1D (5-HT1D) receptors expressed on "pain-responsive" trigeminal primary afferents. In the central terminals of these nociceptors, the receptor is concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from the plasma membrane. Based on this arrangement, we hypothesized that in the resting state the receptor is not available for binding by a triptan, but that noxious stimulation of these afferents could trigger vesicular release of DCVs, thus externalizing the receptor. Here we report that within 5 min of an acute mechanical stimulus to the hindpaw of the rat, there is a significant increase of 5-HT1D-immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord. We suggest that these rapid immunohistochemical changes reflect redistribution of sequestered receptor to the plasma membrane, where it is more readily detected. We also observed divergent changes in 5-HT1D-IR in inflammatory and nerve-injury models of persistent pain, occurring at least in part through the regulation of 5-HT1D-receptor gene expression. Finally, we found that 5-HT1D-IR is unchanged in the spinal cord dorsal horn of mice with a deletion of the gene encoding the neuropeptide substance P. This result differs from that reported for the partial differential-opioid receptor, which is also sorted to DCVs, but is greatly reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered regulation of 5-HT1D-receptor expression underlies the effectiveness of triptans for the treatment of migraine. Moreover, the widespread expression of 5-HT1D receptor in somatic nociceptive afferents suggests that triptans could, in certain circumstances, treat pain in nontrigeminal regions of the body.

Authors+Show Affiliations

Department of Neurology, University of California, San Francisco, San Francisco, California 94158, USA. andrew.ahn@ucsf.eduNo affiliation info available

Pub Type(s)

Journal Article
Research Support, N.I.H., Extramural
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

16899728

Citation

Ahn, Andrew H., and Allan I. Basbaum. "Tissue Injury Regulates Serotonin 1D Receptor Expression: Implications for the Control of Migraine and Inflammatory Pain." The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, vol. 26, no. 32, 2006, pp. 8332-8.
Ahn AH, Basbaum AI. Tissue injury regulates serotonin 1D receptor expression: implications for the control of migraine and inflammatory pain. J Neurosci. 2006;26(32):8332-8.
Ahn, A. H., & Basbaum, A. I. (2006). Tissue injury regulates serotonin 1D receptor expression: implications for the control of migraine and inflammatory pain. The Journal of Neuroscience : the Official Journal of the Society for Neuroscience, 26(32), 8332-8.
Ahn AH, Basbaum AI. Tissue Injury Regulates Serotonin 1D Receptor Expression: Implications for the Control of Migraine and Inflammatory Pain. J Neurosci. 2006 Aug 9;26(32):8332-8. PubMed PMID: 16899728.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Tissue injury regulates serotonin 1D receptor expression: implications for the control of migraine and inflammatory pain. AU - Ahn,Andrew H, AU - Basbaum,Allan I, PY - 2006/8/11/pubmed PY - 2006/9/6/medline PY - 2006/8/11/entrez SP - 8332 EP - 8 JF - The Journal of neuroscience : the official journal of the Society for Neuroscience JO - J. Neurosci. VL - 26 IS - 32 N2 - The anti-migraine action of "triptan" drugs involves the activation of serotonin subtype 1D (5-HT1D) receptors expressed on "pain-responsive" trigeminal primary afferents. In the central terminals of these nociceptors, the receptor is concentrated on peptidergic dense core vesicles (DCVs) and is notably absent from the plasma membrane. Based on this arrangement, we hypothesized that in the resting state the receptor is not available for binding by a triptan, but that noxious stimulation of these afferents could trigger vesicular release of DCVs, thus externalizing the receptor. Here we report that within 5 min of an acute mechanical stimulus to the hindpaw of the rat, there is a significant increase of 5-HT1D-immunoreactivity (IR) in the ipsilateral dorsal horn of the spinal cord. We suggest that these rapid immunohistochemical changes reflect redistribution of sequestered receptor to the plasma membrane, where it is more readily detected. We also observed divergent changes in 5-HT1D-IR in inflammatory and nerve-injury models of persistent pain, occurring at least in part through the regulation of 5-HT1D-receptor gene expression. Finally, we found that 5-HT1D-IR is unchanged in the spinal cord dorsal horn of mice with a deletion of the gene encoding the neuropeptide substance P. This result differs from that reported for the partial differential-opioid receptor, which is also sorted to DCVs, but is greatly reduced in preprotachykinin mutant mice. We suggest that a "pain"-triggered regulation of 5-HT1D-receptor expression underlies the effectiveness of triptans for the treatment of migraine. Moreover, the widespread expression of 5-HT1D receptor in somatic nociceptive afferents suggests that triptans could, in certain circumstances, treat pain in nontrigeminal regions of the body. SN - 1529-2401 UR - https://www.unboundmedicine.com/medline/citation/16899728/Tissue_injury_regulates_serotonin_1D_receptor_expression:_implications_for_the_control_of_migraine_and_inflammatory_pain_ L2 - http://www.jneurosci.org/cgi/pmidlookup?view=long&pmid=16899728 DB - PRIME DP - Unbound Medicine ER -