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

Headache. 2011 Nov-Dec;51(10):1511-9. doi: 10.1111/j.1526-4610.2011.02011.x.

Abstract

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.

Publication types

  • Research Support, N.I.H., Extramural

MeSH terms

  • Animals
  • Capsaicin / pharmacology*
  • Male
  • Proto-Oncogene Proteins c-fos / metabolism*
  • Rats
  • Rats, Wistar
  • Receptors, Serotonin / metabolism*
  • Trigeminal Caudal Nucleus / drug effects
  • Trigeminal Caudal Nucleus / metabolism*

Substances

  • Proto-Oncogene Proteins c-fos
  • Receptors, Serotonin
  • serotonin 7 receptor
  • Capsaicin