K A Carrigan1, C J Nelson, D T Lysle. 1. Department of Psychology, University of North Carolina at Chapel Hill, 27599-3270, USA. kelly@isis.unc.edu
Abstract
RATIONALE: Although there is evidence that central opioid receptors are involved in immunomodulation, it has been only recently that an endogenous agonist, designated endomorphin-1, possessing high selectivity and affinity for the mu opioid receptor has been identified. OBJECTIVE: The present study assesses the immunomodulatory effects of endomorphin- in the rat and provides further evaluation of the antinociceptive effects of endomorphin-1. METHODS: Rats were surgically implanted with cannulae directed at the lateral cerebral ventricle. Animals received vehicle or endomorphin-1 at doses of 31.63 or 56.23 microg (ICV) and were tested for antinociception in two different assays, the warm water tail withdrawal procedure and the hotplate assay. Additional studies assessed the effect of naltrexone on the antinociception produced by endomorphin-1 in both antinociceptive assessments. Assessments of immune status following endomorphin-1 treatment included measurements of splenic natural killer cell activity, production of interferon-y, and lymphocyte proliferative responses to mitogenic stimulation by Con-A, LPS, and the microbial superantigen, TSST-1. RESULTS: Endomorphin-1 induced significant and naltrexone reversible antinociception 30 and 60 min following drug administration, as measured by the hotplate assay and warm water tail withdrawal procedure. In marked contrast, endomorphin-1 did not produce immunomodulatory effects up to 120 min following ICV administration. CONCLUSIONS: Endomorphin-1 produces antinociception but does not induce immunomodulatory effects in the rat. These findings suggest that it is possible to develop therapeutic strategies for separating antinociception and immunomodulatory properties through the mu opioid receptor.
RATIONALE: Although there is evidence that central opioid receptors are involved in immunomodulation, it has been only recently that an endogenous agonist, designated endomorphin-1, possessing high selectivity and affinity for the mu opioid receptor has been identified. OBJECTIVE: The present study assesses the immunomodulatory effects of endomorphin- in the rat and provides further evaluation of the antinociceptive effects of endomorphin-1. METHODS:Rats were surgically implanted with cannulae directed at the lateral cerebral ventricle. Animals received vehicle or endomorphin-1 at doses of 31.63 or 56.23 microg (ICV) and were tested for antinociception in two different assays, the warm water tail withdrawal procedure and the hotplate assay. Additional studies assessed the effect of naltrexone on the antinociception produced by endomorphin-1 in both antinociceptive assessments. Assessments of immune status following endomorphin-1 treatment included measurements of splenic natural killer cell activity, production of interferon-y, and lymphocyte proliferative responses to mitogenic stimulation by Con-A, LPS, and the microbial superantigen, TSST-1. RESULTS: Endomorphin-1 induced significant and naltrexone reversible antinociception 30 and 60 min following drug administration, as measured by the hotplate assay and warm water tail withdrawal procedure. In marked contrast, endomorphin-1 did not produce immunomodulatory effects up to 120 min following ICV administration. CONCLUSIONS: Endomorphin-1 produces antinociception but does not induce immunomodulatory effects in the rat. These findings suggest that it is possible to develop therapeutic strategies for separating antinociception and immunomodulatory properties through the mu opioid receptor.
Authors: Huina Zhang; Mary M Torregrossa; Emily M Jutkiewicz; Yong-Gong Shi; Kenner C Rice; James H Woods; Stanley J Watson; M C Ko Journal: Eur J Neurosci Date: 2006-02 Impact factor: 3.386