OBJECTIVE: To explore whether pharmacological stimulation of the 5-hydroxytryptamine(7) (5-HT(7) ) receptor modulates Fos-like immunoreactivity in the trigeminal nucleus caudalis of rats. BACKGROUND: The serotonin 5-HT(7) 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-HT(7) 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-HT(7) receptor agonist, LP-211, in the absence and the presence of intracisternal capsaicin, respectively. The agonist effect was characterized with the 5-HT(7) 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-HT(7) 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.
OBJECTIVE: To explore whether pharmacological stimulation of the 5-hydroxytryptamine(7) (5-HT(7) ) receptor modulates Fos-like immunoreactivity in the trigeminal nucleus caudalis of rats. BACKGROUND: The serotonin 5-HT(7) 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-HT(7) 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-HT(7) receptor agonist, LP-211, in the absence and the presence of intracisternal capsaicin, respectively. The agonist effect was characterized with the 5-HT(7) 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-HT(7) 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.
Authors: Ian T Forbes; Sara Douglas; Andrew D Gribble; Robert J Ife; Andrew P Lightfoot; Ashley E Garner; Graham J Riley; Phillip Jeffrey; Alexander J Stevens; Tania O Stean; David R Thomas Journal: Bioorg Med Chem Lett Date: 2002-11-18 Impact factor: 2.823
Authors: Hayrunnisa Bolay; Uwe Reuter; Andrew K Dunn; Zhihong Huang; David A Boas; Michael A Moskowitz Journal: Nat Med Date: 2002-02 Impact factor: 53.440
Authors: Patricio Atanes; Enza Lacivita; Javier Rodríguez; José Brea; Javier Burgueño; José Miguel Vela; María Isabel Cadavid; María Isabel Loza; Marcello Leopoldo; Marián Castro Journal: Pharmacol Res Perspect Date: 2013-12-05