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Olvanil acts on transient receptor potential vanilloid channel 1 and cannabinoid receptors to modulate neuronal transmission in the trigeminovascular system

Hoffmann, Jan; Supronsinchai, Weera; Andreou, Anna P.; Summ, Oliver; Akerman, Simon; Goadsby, Peter J.*

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doi: 10.1016/j.pain.2012.07.006
Article

Summary The transient receptor potential vanilloid channel 1 (TRPV1) receptor agonist olvanil inhibits neuronal activity in the trigeminocervical complex acting on vanilloid and cannabinoid receptor systems.

ABSTRACT The transient receptor potential vanilloid channel 1 (TRPV1) is a nociceptive transducer located on nociceptive neurons. TRPV1 channels located on peripheral neurons mainly transduce the sense of heat and are also activated by low pH or capsaicin. The role of centrally located TRPV1 channels is not fully understood. Likewise their importance in pain syndromes of central origin, such as migraine, is not known. Experimental data suggest a relationship to migraine. However, experimental studies with TRPV1 receptor antagonists indicate that the receptor may not be a useful target for new acute migraine treatments. Any potential role for the receptor in the chronification of migraine has not been investigated. The present study aimed at analyzing the use of the TRPV1 channel as a target to desensitize trigeminal neurons and thereby inhibit neuronal activity in the trigeminocervical complex. The TRPV1 receptor agonist olvanil was used for desensitization because, as compared with capsaicin, it is non-noxious and lacks capsaicin’s pungency and CGRP release potential. We further investigated a possible effect of olvanil on cannabinoid (CB1) receptors, as an interaction between both receptor systems has been described previously. The results show that olvanil dose-dependently inhibited spontaneous and stimulus-induced activity within the trigeminocervical complex, whereas it had no effect on CSD susceptibility. We further demonstrated that the inhibiting effect of olvanil is mediated by vanilloid and cannabinoid receptor systems, thereby using the synergistic effects this dual mechanism offers. Curiously, TRPV1 receptor agonism may have anti-nociceptive properties through central mechanisms that would be of considerable interest to elucidate.

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

UCSF Headache Program, Department of Neurology, University of California San Francisco, San Francisco, CA, USA

*Corresponding author. Address: UCSF Headache Program, 1701 Divisadero Street, Suite 480, San Francisco, CA 94115, USA.

E-mail address: pgoadsby@headache.ucsf.edu

Article history: Received 1 January 2012; Received in revised form 29 June 2012; Accepted 5 July 2012.

© 2012 Lippincott Williams & Wilkins, Inc.
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