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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) A correction has been published 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 (31) Citing Articles via Google Scholar Google Scholar Articles by Joshi, S. K. Articles by Gebhart, G. F. Search for Related Content PubMed PubMed Citation Articles by Joshi, S. K. Articles by Gebhart, G. F.

 Previous Article  |  Next Article 

The Journal of Neuroscience, August 1, 2000, 20(15):5874-5879

-Opioid Receptor Agonists Modulate Visceral Nociception at a Novel, Peripheral Site of Action

S. K. Joshi¹, Xin Su¹, Frank Porreca², and G. F. Gebhart¹

¹ Department of Pharmacology, College of Medicine, The University of Iowa, Iowa City, Iowa 52242, and ² Department of Pharmacology, University of Arizona, Tucson, Arizona 85721

-opioid receptor agonists (-ORAs) have been shown to modulate visceral nociception through an interaction with a peripheral, possibly novel, -opioid-like receptor. We used in the present experiments an antisense strategy to further explore the hypothesis that -ORA effects in the colon are produced at a site different from the cloned -opioid receptor (KOR). An antisense oligodeoxynucleotide (ODN) to the cloned rat KOR was administered intrathecally (12.5 µg, twice daily for 4 d) to specifically knock-down the cloned KOR. Efficacy of the KOR antisense ODN treatment was behaviorally evaluated by assessing the antinociceptive effects of peripherally administered - (EMD 61,753 and U 69,593), µ- (DAMGO) and - (deltorphin) ORAs in the formalin test. Intrathecal antisense, but not mismatch ODN blocked the actions of EMD 61,753 and U 69,593 without affecting the actions of DAMGO or deltorphin; a complete recovery of antinociceptive actions of the -ORA EMD 61,753 was observed 10 d after the termination of antisense ODN treatment. In contrast, the ability of EMD 61,753 to dose-dependently attenuate responses of pelvic nerve afferent fibers to noxious colonic distension was unaffected in the same rats in which the antisense ODN effectively knocked-down the KOR as assessed in the formalin test. Additionally, Western blot analysis demonstrated a significant downregulation of KOR protein in the L4-S1 dorsal root ganglia of antisense, but not mismatch ODN-treated rats. The present results support the existence of a non--opioid receptor site of action localized in the colon.

Key words: peripheral opioids; nociception; colorectal distension; formalin test; antisense; visceral pain

---

Copyright © 2000 Society for Neuroscience  0270-6474/00/20155874-06$05.00/0

This article has been cited by other articles:

				T. Kitamura, M. Ogawa, and Y. Yamada The Individual and Combined Effects of U50,488, and Flurbiprofen Axetil on Visceral Pain in Conscious Rats Anesth. Analg., June 1, 2009; 108(6): 1964 - 1966. [Abstract] [Full Text] [PDF]

				H. U. De Schepper, B. Y. De Winter, L. Van Nassauw, J.-P. Timmermans, A. G. Herman, P. A. Pelckmans, and J. G. De Man TRPV1 receptors on unmyelinated C-fibres mediate colitis-induced sensitization of pelvic afferent nerve fibres in rats J. Physiol., November 1, 2008; 586(21): 5247 - 5258. [Abstract] [Full Text] [PDF]

				N. Jimenez, M. M. Puig, and O. Pol Antiexudative Effects of Opioids and Expression of {kappa}- and {delta}- Opioid Receptors during Intestinal Inflammation in Mice: Involvement of Nitric Oxide J. Pharmacol. Exp. Ther., January 1, 2006; 316(1): 261 - 270. [Abstract] [Full Text] [PDF]

				S. K. Joshi, K. Lamb, K. Bielefeldt, and G. F. Gebhart Arylacetamide {kappa}-Opioid Receptor Agonists Produce a Tonic- and Use-Dependent Block of Tetrodotoxin-Sensitive and -Resistant Sodium Currents in Colon Sensory Neurons J. Pharmacol. Exp. Ther., October 1, 2003; 307(1): 367 - 372. [Abstract] [Full Text] [PDF]

				O. Pol, J. R. Palacio, and M. M. Puig The Expression of {delta}- and {kappa}-Opioid Receptor Is Enhanced during Intestinal Inflammation in Mice J. Pharmacol. Exp. Ther., August 1, 2003; 306(2): 455 - 462. [Abstract] [Full Text] [PDF]

				S. K. Joshi and G. F. Gebhart Nonopioid Actions of U50,488 Enantiomers Contribute to Their Peripheral Cutaneous Antinociceptive Effects J. Pharmacol. Exp. Ther., June 1, 2003; 305(3): 919 - 924. [Abstract] [Full Text] [PDF]

				J. N. Sengupta, B. K. Medda, and R. Shaker Effect of GABAB receptor agonist on distension-sensitive pelvic nerve afferent fibers innervating rat colon Am J Physiol Gastrointest Liver Physiol, December 1, 2002; 283(6): G1343 - G1351. [Abstract] [Full Text] [PDF]

				X. Su, S. K. Joshi, S. Kardos, and G. F. Gebhart Sodium Channel Blocking Actions of the kappa -Opioid Receptor Agonist U50,488 Contribute to Its Visceral Antinociceptive Effects J Neurophysiol, March 1, 2002; 87(3): 1271 - 1279. [Abstract] [Full Text] [PDF]

				Y. Ji and R. J. Traub Spinal NMDA Receptors Contribute to Neuronal Processing of Acute Noxious and Nonnoxious Colorectal Stimulation in the Rat J Neurophysiol, October 1, 2001; 86(4): 1783 - 1791. [Abstract] [Full Text] [PDF]

				R. G. Hill Book Review: Molecular Basis for the Perception of Pain Neuroscientist, August 1, 2001; 7(4): 282 - 292. [Abstract] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help