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Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats.
Neuroscience. 2007 Nov 30; 150(1):194-201.N

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.

Authors+Show Affiliations

Department of Physiology, University of Szeged, Dóm tér 10., H-6720 Szeged, Hungary. dux@phys.szote.u-szeged.hu <dux@phys.szote.u-szeged.hu>No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17920775

Citation

Dux, M, et al. "Loss of Capsaicin-induced Meningeal Neurogenic Sensory Vasodilatation in Diabetic Rats." Neuroscience, vol. 150, no. 1, 2007, pp. 194-201.
Dux M, Rosta J, Pintér S, et al. Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats. Neuroscience. 2007;150(1):194-201.
Dux, M., Rosta, J., Pintér, S., Sántha, P., & Jancsó, G. (2007). Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats. Neuroscience, 150(1), 194-201.
Dux M, et al. Loss of Capsaicin-induced Meningeal Neurogenic Sensory Vasodilatation in Diabetic Rats. Neuroscience. 2007 Nov 30;150(1):194-201. PubMed PMID: 17920775.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Loss of capsaicin-induced meningeal neurogenic sensory vasodilatation in diabetic rats. AU - Dux,M, AU - Rosta,J, AU - Pintér,S, AU - Sántha,P, AU - Jancsó,G, Y1 - 2007/09/12/ PY - 2007/03/01/received PY - 2007/08/30/revised PY - 2007/09/13/accepted PY - 2007/10/9/pubmed PY - 2008/3/29/medline PY - 2007/10/9/entrez SP - 194 EP - 201 JF - Neuroscience JO - Neuroscience VL - 150 IS - 1 N2 - 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. SN - 0306-4522 UR - https://www.unboundmedicine.com/medline/citation/17920775/Loss_of_capsaicin_induced_meningeal_neurogenic_sensory_vasodilatation_in_diabetic_rats_ DB - PRIME DP - Unbound Medicine ER -