Source of financial support: NIH Research Grant # R01TW006622 funded by the Fogarty International Center, the Office of Research on Women's Health, and the Office of Dietary Supplements.
Increase of Capsaicin-Induced Trigeminal Fos-Like Immunoreactivity by 5-HT7 Receptors
Article first published online: 14 NOV 2011
© 2011 American Headache Society
Headache: The Journal of Head and Face Pain
Volume 51, Issue 10, pages 1511–1519, November/December 2011
How to Cite
Martínez-García, E., Leopoldo, M., Lacivita, E. and Terrón, J. A. (2011), Increase of Capsaicin-Induced Trigeminal Fos-Like Immunoreactivity by 5-HT7 Receptors. Headache: The Journal of Head and Face Pain, 51: 1511–1519. doi: 10.1111/j.1526-4610.2011.02011.x
Conflict of Interest: No conflict.
- Issue published online: 14 NOV 2011
- Article first published online: 14 NOV 2011
- Accepted for publication June 9, 2011.
- 5-hydroxytryptamine7 receptor;
- Fos-like immunoreactivity;
- trigeminal nucleus caudalis;
- cephalic pain;
Objective.— To explore whether pharmacological stimulation of the 5-hydroxytryptamine7 (5-HT7) receptor modulates Fos-like immunoreactivity in the trigeminal nucleus caudalis of rats.
Background.— The serotonin 5-HT7 receptor was proposed to be involved in migraine pathogenesis and evidence suggests it plays a role in peripheral nociception and hyperalgesia through an action on sensory afferent neurons.
Methods.— The potential activating or sensitizing role of 5-HT7 receptors on trigeminal sensory neurons, as visualized by Fos-like immunoreactivity in the superficial layers of the trigeminal nucleus caudalis in rats, was investigated using the 5-HT7 receptor agonist, LP-211, in the absence and the presence of intracisternal capsaicin, respectively. The agonist effect was characterized with the 5-HT7 receptor antagonist, SB-656104. Male Wistar rats received a subcutaneous injection of LP-211, SB-656104, and SB-656104 + LP-211. They were then anesthetized and prepared to receive an intracisternal injection of capsaicin or its vehicle. Animals were perfused and brains removed; sections of the brain stem from the area postrema to the CI level were obtained and processed for Fos immunohistochemistry.
Results.— Capsaicin but not its vehicle induced Fos-like immunoreactivity within laminae I and II of trigeminal nucleus caudalis. Pretreatment with LP-211 had no effect on Fos-like immunoreactivity but strongly increased the response produced by capsaicin; this effect was abolished by SB-656104. Interestingly, capsaicin-induced Fos-like immunoreactivity was abolished by SB-656104 pretreatment thus suggesting involvement of endogenous 5-HT.
Conclusions.— Data suggest that 5-HT7 receptors increase activation of meningeal trigeminovascular afferents and/or transmission of nociceptive information in the brain stem. This mechanism could be relevant in migraine and its prophylactic treatment.