QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science 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 Web of Science (21) Citing Articles via Google Scholar Google Scholar Articles by Khodorova, A. Articles by Davar, G. Search for Related Content PubMed PubMed Citation Articles by Khodorova, A. Articles by Davar, G.

 Previous Article  |  Next Article 

The Journal of Neuroscience, September 1, 2002, 22(17):7788-7796

Local Injection of a Selective Endothelin-B Receptor Agonist Inhibits Endothelin-1-Induced Pain-Like Behavior and Excitation of Nociceptors in a Naloxone-Sensitive Manner

Alla Khodorova^{1, 2, *}, Moin U. Fareed^{1, *}, Alexander Gokin^{1, 2, *}, Gary R. Strichartz^{1, 2, 3}, and Gudarz Davar¹

¹ Molecular Neurobiology of Pain, ² Sensory Neurophysiology Laboratories of the Pain Research Center, Department of Anesthesiology, Perioperative and Pain Medicine, Brigham and Women's Hospital, and ³ Department of Biological Chemistry and Molecular Pharmacology, Harvard Medical School, Boston, Massachusetts 02115

We showed previously that subcutaneous injection of the injury-associated peptide mediator endothelin-1 (ET-1) into the rat plantar hindpaw produces pain behavior and selective excitation of nociceptors, both through activation of ET_A receptors likely on nociceptive terminals. The potential role of ET_B receptor activation in these actions of ET-1-has not been examined. Therefore, in these experiments, we studied the effect of blocking or activating ET_B receptors on ET-1-induced hindpaw flinching and excitation of nociceptors in rats. An ET_B receptor-selective antagonist, BQ-788 (3 mM), coinjected with ET-1 (200 µM) reduced the time-to-peak of flinching and significantly enhanced the average maximal flinch frequency (MFF). In contrast, coinjection of an ET_B receptor selective agonist, IRL-1620 (100 or 200 µM), with ET-1 reduced the average MFF and the average total number of flinches. Interestingly, this unexpected inhibitory effect of IRL-1620 was prevented by the nonselective opioid receptor antagonist naloxone (2.75 mM). To confirm these inhibitory actions, we studied the effects of IRL-1620 on ET-1-induced spike responses in single, physiologically characterized nociceptive C-fibers. IRL-1620 suppressed spike responses to ET-1 in all (n = 12) C-units, with mean and maximum response frequencies of 0.08 ± 0.02 and 1.5 ± 0.4 impulses/sec versus 0.32 ± 0.07 and 4.17 ± 0.17 impulses/sec for ET-1 alone. In additional support of the behavioral results, coinjection of naloxone (2.75 mM) completely prevented this inhibitory action of IRL-1620. These results establish that ET_B receptor activation inhibits ET-1-induced pain behavior and nociception in a naloxone-sensitive manner and point to a previously unrecognized dual modulation of acute nociceptive signaling by ET_A and ET_B receptors in cutaneous tissues.

Key words: nociception; analgesia; G-protein; endothelin-1; opioid; potassium channel

---

^* A.K., M.U.F., and A.G. contributed equally to this work.

---

Copyright © 2002 Society for Neuroscience  0270-6474/02/22177788-09$05.00/0

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]

				D. Fraga, R. R. Machado, L. C. Fernandes, G. E. P. Souza, and A. R. Zampronio Endogenous opioids: role in prostaglandin-dependent and -independent fever Am J Physiol Regulatory Integrative Comp Physiol, February 1, 2008; 294(2): R411 - R420. [Abstract] [Full Text] [PDF]

				U. C. Kopp, M. Z. Cicha, and L. A. Smith Activation of Endothelin-A Receptors Contributes to Angiotensin-Induced Suppression of Renal Sensory Nerve Activation Hypertension, January 1, 2007; 49(1): 141 - 147. [Abstract] [Full Text] [PDF]

				U. C. Kopp, M. Z. Cicha, and L. A. Smith Differential effects of endothelin on activation of renal mechanosensory nerves: stimulatory in high-sodium diet and inhibitory in low-sodium diet Am J Physiol Regulatory Integrative Comp Physiol, November 1, 2006; 291(5): R1545 - R1556. [Abstract] [Full Text] [PDF]

				P. G. Trentin, M. B. Fernandes, P. D'Orleans-Juste, and G. A. Rae Endothelin-1 causes pruritus in mice. Experimental Biology and Medicine, June 1, 2006; 231(6): 1146 - 1151. [Abstract] [Full Text] [PDF]

				K. Balonov, A. Khodorova, and G. R. Strichartz Tactile Allodynia Initiated by Local Subcutaneous Endothelin-1 Is Prolonged by Activation of TRPV-1 Receptors. Experimental Biology and Medicine, June 1, 2006; 231(6): 1165 - 1170. [Abstract] [Full Text] [PDF]

				W. A. Verri Jr, I. R. S. Schivo, T. M. Cunha, F. Y. Liew, S. H. Ferreira, and F. Q. Cunha Interleukin-18 Induces Mechanical Hypernociception in Rats via Endothelin Acting on ETB Receptors in a Morphine-Sensitive Manner J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 710 - 717. [Abstract] [Full Text] [PDF]

				K. Garber Why it Hurts: Researchers Seek Mechanisms of Cancer Pain J Natl Cancer Inst, June 4, 2003; 95(11): 770 - 772. [Full Text]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help