Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats

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Abstract

Neuropathic alterations of sensory nerves involved in the mediation of neurogenic inflammation of the meninges may contribute to the increased incidence of headaches in diabetics. In the rat, activation of capsaicin-sensitive nociceptors, which express the transient receptor potential vanilloid type 1 (TRPV1) receptor, induces meningeal vasodilatation, a significant component of neurogenic inflammation, through the release of calcitonin gene-related peptide (CGRP). This study examines the effects of streptozotocin-induced diabetes on TRPV1 receptor-mediated neurogenic sensory vasodilatation, CGRP release and nerve fiber density in the rat dura mater. In a cranial window preparation, epidural application of capsaicin (10-7 M) produced distinct vasodilatory responses in control animals as measured by laser Doppler flowmetry. In diabetic rats, capsaicin-induced vasodilatation was reduced or even abolished 6, but not 2 or 4 weeks after diabetes induction. In contrast, vasoconstriction, a non-neurogenic response to capsaicin at a higher concentration (10-5 M), was not altered in diabetic rats. The vasodilatory effects of histamine (10-5 M), acetylcholine (10-4 M) and CGRP (10-5 M) were similar in control, diabetic and insulin-treated diabetic animals. In diabetic rats, a significant decrease in the capsaicin-evoked release of CGRP and reduction in the density of TRPV1-immunoreactive (IR) nerves were demonstrated. Treatment of the diabetic rats with insulin restored both the vasodilatory response and the capsaicin-induced CGRP release toward control values. In conclusion, this study revealed a marked impairment of meningeal TRPV1-IR nerves in streptozotocin diabetic rats by showing reduced neurogenic sensory vasodilatation, decreased capsaicin-evoked CGRP release and reduction in the number of TRPV1-IR nerve fibers of the dura mater. The findings suggest that capsaicin-sensitive afferents may play an important role in meningeal nociceptor function and their dysfunction, e.g. due to a limited removal of inflammatory mediators and/or tissue metabolites from the meningeal tissue, may contribute to the enhanced incidence of headaches in diabetics.

Original languageEnglish
Pages (from-to)194-201
Number of pages8
JournalNeuroscience
Volume150
Issue number1
DOIs
Publication statusPublished - Nov 30 2007

Fingerprint

Capsaicin
Vasodilation
Calcitonin Gene-Related Peptide
Neurogenic Inflammation
Dura Mater
Nociceptors
Nerve Fibers
Headache
Insulin
Meninges
Laser-Doppler Flowmetry
Experimental Diabetes Mellitus
Incidence
Streptozocin
Vasoconstriction
Histamine
Acetylcholine
vanilloid receptor subtype 1

Keywords

  • blood flow
  • calcitonin gene-related peptide
  • headache
  • laser Doppler flowmetry
  • transient receptor potential vanilloid type 1 receptor

ASJC Scopus subject areas

  • Neuroscience(all)

Cite this

Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats. / Dux, M.; Rosta, J.; Pintér, S.; Sántha, P.; Jancsó, G.

In: Neuroscience, Vol. 150, No. 1, 30.11.2007, p. 194-201.

Research output: Contribution to journalArticle

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AU - Jancsó, G.

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