| Abstract No.: | A-D1153 |
| Country: | Canada |
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| Title: | ON A ROLE FOR ADRENOMEDULLIN IN THE DEVELOPMENT OF MORPHINE TOLERANCE |
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| Authors/Affiliations: | 1 Yanguo Hong*; 2 Peiwen Chen; 1 Weiya Ma; 1 Jean-Guy Chabot; 1 Rémi Quirion;
1 Douglas Mental Health University Institute, Montreal, QC, Canada; 2 Fujian Normal University, China
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| Content: | Yanguo Hong1,2, Peiwen Chen2, Weiya Ma1, Jean-Guy Chabot1 and Remi Quirion1 1Douglas Mental Health University Institute, Department of Psychiatry, McGill University, Montreal, Quebec H4H 1R3, Canada and 2Department of Anatomy and Physiology, Fujian Normal University, Fuzhou, Fujian, 350108, China
The development of opioid tolerance is usually associated with enhanced excitatory neurotransmission. Since adrenomedullin-like immunoreactivity (AM-IR), a pain-producing peptide, was enhanced in the spinal cord and dorsal root ganglia (DRG) during chronic inflammation (Hong et al., 2007, Soc. Neurosci. Abstr.33, 25), we hypothesized that AM at the spinal level may be up-regulated in morphine tolerance. Intrathecal administration of morphine (20 µg, daily) for 6 days induced a progressive decline of its antinociceptive effect and a right shift of the morphine dose¨Cresponse curve as measured by the tail flick assay. Co-administration of the AM antagonist AM22-52 prevented these responses in a dose-dependent manner (2-10 nmol, i.t.). However, acute administration of AM22-52 did not alter the antinociceptive efficacy of morphine. Chronic treatment with morphine evoked increases in the expression of AM-like immunoreactivity (AM-IR) in the superficial layers of the spinal dorsal horn and small, medium and large subpopulations of DRG neurons. Furthermore, chronic administration of morphine evoked an increase in the expression of neuronal nitric oxide synthase (nNOS) in small and medium DRG neurons. Co-treatment with AM22-52 (10 nmol, i.t.) completely abolished morphine-evoked increase in AM-IR and nNOS in the spinal cord or DRG. The present study suggests that increase in AM levels at the spinal level is involved in the development of morphine tolerance, and that the effect of AM is mediated by the activation of NO pathway. (Supported by the Canadian Institutes of Health Research and the National Natural Science Foundation of China)
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