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Intrathecal Clonidine Decreases Spinal Nitric Oxide Release in a Rat Model of Complete Freund's Adjuvant Induced Inflammatory Pain

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Abstract

A long-lasting antihyperalgesic effect has been demonstrated for intrathecal (IT) clonidine, an alpha2-adrenergic agonist. In the present study, the mechanism and antihyperalgesic effects of IT clonidine were examined post-treatment in a rat model of Complete Freund's Adjuvant (CFA)-induced inflammatory hyperalgesia. Using a chronic model of spinal cord dialysis, we examined the effect of the adjuvant-induced inflammation on spinal release of nitric oxide (NO) and the development of chronic pain and assessed the antinociceptive effects and mechanisms of the alpha2-adrenergic agonist, clonidine (IT). Chronic, persistent inflammatory pain was induced by left hind paw injection of 0.3 ml CFA prepared in a mixture with Mycobacterium butyricum. Rats were randomly assigned to groups receiving IT clonidine in discrete doses of 1, 10 or 50 μg, 3 or 24 hr post-inflammation. Measurement of total NO x (NO + \({\text{NO}}_{2 - } + {\text{NO}}_{3 - } \)) was used to determine NO release into the cerebrospinal fluid. Rat thermal antinociception was assessed using a radiant heat thermal hyperalgesia model. CFA injection resulted in significant thermal hyperalgesia throughout the four days of observation. A dose-dependent suppression of thermal hyperalgesia and spinal NO release was observed after IT clonidine treatment. Evidence from this CFA-induced inflammatory pain model suggests that clonidine's spinal antihyperalgesic mechanisms act through inhibition of spinal NO release.

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Authors and Affiliations

  1. Anesthesiology Research Laboratory, Kaohsiung Chang Gung Memorial Hospital, Chang Gung University, Kaohsiung Hsien, 833, Taiwan

    C.-R. Lin, Y.-C. Chuang, C.-J. Wang & L.-C. Yang

  2. National Sun-Yat Sen University, Kaohsiung, 804, Taiwan

    C.-R. Lin & J.-T. Cheng

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Lin, CR., Chuang, YC., Cheng, JT. et al. Intrathecal Clonidine Decreases Spinal Nitric Oxide Release in a Rat Model of Complete Freund's Adjuvant Induced Inflammatory Pain. Inflammation 26, 161–166 (2002). https://doi.org/10.1023/A:1016563628274

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