HOME HELP FEEDBACK SUBSCRIPTIONS ARCHIVE SEARCH TABLE OF CONTENTS		QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

This Article Full Text Free Full Text (PDF) Free Alert me when this article is cited Alert me if a correction is posted Services Similar articles in this journal Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Google Scholar Google Scholar Articles by Chichorro, J. G. Articles by Rae, G. A. Search for Related Content PubMed PubMed Citation Articles by Chichorro, J. G. Articles by Rae, G. A.

---

PAIN

Endothelin ET_B Receptor Antagonist Reduces Mechanical Allodynia in Rats with Trigeminal Neuropathic Pain

Juliana Geremias Chichorro^*, Aleksander Roberto Zampronio and Giles Alexander Rae^*,1

^* Department of Pharmacology, Universidade Federal de Santa Catarina, Florianópolis, Santa Catarina, Brazil; and Department of Pharmacology, Universidade Federal do Paraná, Curitiba, Paraná, Brazil

To whom requests for reprints should be addressed at ¹ Universidade Federal de Santa Catarina, Center of Biological Sciences, Block D, Trindade, Florianópolis, SC 88040–900, Brazil. E-mail address: garae{at}farmaco.ufsc.br

Abstract

Trigeminal neuropathic pain, which is associated with marked orofacial mechanical allodynia, is frequently refractory to currently available drugs. Because endothelins (ETs) can contribute to nociceptive changes in animal models of inflammatory, cancer, and diabetic neuropathic pain, the present study evaluated the influence of ET_A and ET_B receptor antagonists on orofacial mechanical allodynia in a rat model of trigeminal neuropathic pain. Unilateral constriction (C) of the infraorbital nerve (ION) caused pronounced and sustained bilateral mechanical allodynia, evaluated by application of von Frey hairs to the vibrissal pad. Mechanical allodynia on postoperative days 12–15 after nerve injury was abolished for up to 90 mins by subcutaneous administration of 2.5 mg/kg morphine, but was fully refractory to intravenous (iv) administration of 10 mg/kg of the dual ET_A plus ET_B or selective ET_A receptor antagonists, bosentan and atrasentan, respectively. In sharp contrast, iv administration of 20 mg/kg of the selective ET_B receptor antagonist, A-192621, caused a net 61 ± 15% reduction of mechanical threshold, lasting 2 hrs. Co-injection of atrasentan plus A-192621 did not modify ION injury-induced mechanical allodynia. Injection of 10 pmol ET-1 into the upper lip of naive rats caused ipsilateral mechanical allodynia lasting up to 5 hrs. Thus, ET_B receptor–mediated mechanisms contribute to orofacial mechanical allodynia induced by CION injury, but, some-how, functional ET_A receptors are required for expression of the antiallodynic effect of ET_B receptor blockade.

Key Words: trigeminal neuropathic pain • endothelin • rats • mechanical allodynia

This article has been cited by other articles:

				D. T. Hamamoto, S. G. Khasabov, D. M. Cain, and D. A. Simone Tumor-Evoked Sensitization of C Nociceptors: A Role for Endothelin J Neurophysiol, October 1, 2008; 100(4): 2300 - 2311. [Abstract] [Full Text] [PDF]