Increase of capsaicin-induced trigeminal Fos-like immunoreactivity by 5-HT(7) receptors

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.