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Increase of Capsaicin-Induced Trigeminal Fos-Like Immunoreactivity by 5-HT7 Receptors

Authors

  • Esther Martínez-García PhD,

    1. From the Department of Pharmacology, Cinvestav-IPN, Mexico D.F., Mexico (J.A. Terrón and E. Martínez-García); Dipartimento Farmaco-Chimico, Universitá degli Studi di Bari, Bari, Italy (M. Leopoldo and E. Lacivita).
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  • Marcello Leopoldo MD,

    1. From the Department of Pharmacology, Cinvestav-IPN, Mexico D.F., Mexico (J.A. Terrón and E. Martínez-García); Dipartimento Farmaco-Chimico, Universitá degli Studi di Bari, Bari, Italy (M. Leopoldo and E. Lacivita).
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  • Enza Lacivita PhD,

    1. From the Department of Pharmacology, Cinvestav-IPN, Mexico D.F., Mexico (J.A. Terrón and E. Martínez-García); Dipartimento Farmaco-Chimico, Universitá degli Studi di Bari, Bari, Italy (M. Leopoldo and E. Lacivita).
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  • José A. Terrón PhD

    Corresponding author
    1. From the Department of Pharmacology, Cinvestav-IPN, Mexico D.F., Mexico (J.A. Terrón and E. Martínez-García); Dipartimento Farmaco-Chimico, Universitá degli Studi di Bari, Bari, Italy (M. Leopoldo and E. Lacivita).
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  • 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.

  • Conflict of Interest: No conflict.

José A. Terrón, Department of Pharmacology, Cinvestav-IPN, Av. IPN 2508, col. San Pedro Zacatenco, Mexico DF 07360, Mexico, email: jterron@cinvestav.mx

Abstract

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.

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