Study for the Antinociceptive Effect and Toxicity of Chronic Intrathecal Infusion of Cannabinoids in Rats / 대한통증학회지

BACKGROUND: Cannabinoids have shown antinociceptive action. The aims of this study were to examine the effect of chronic infusion of a cannabinoids receptors agonist (WIN 55, 212-2) for thermal nociception at the spinal level, and to also observe the development of toxicity. METHODS: Male Sprague-Dawley rats were implanted with lumbar intrathecal catheters with the nociceptive response (withdrawal response latency) determined by exposing the plantar surface of the hindpaw to radiant heat. Initially, the effect of intrathecal WIN 55, 212-2 was evaluated followed by the change in the effect at 1, 2, 3 and 4 weeks after repeated infusion. Finally, the histopathological findings were assessed 1 and 4 weeks following the infusion of WIN 55, 212-2. RESULTS: Intrathecal WIN 55, 212-2 was found to produce a limited antinociception during the thermal test. %MPE of WIN 55, 212-2 at 1, 2, 3, and 4 weeks after infusion was not different from each other. No abnormal pathological findings were observed following a chronic intrathecal infusion of WIN 55, 212-2. CONCLUSIONS: WIN 55, 212-2, a cannabinoids receptors agonist, may be useful in the management of thermal nociception, without changing the effectiveness or causing the toxicity following a chronic infusion at the spinal level.

Localization of Cyclooxygenase Isozymes in Dermal Wound Healing in Mouse

Cyclooxygenase(COX)-1 and COX-2 expression in dermal wound healing of mouse was detected by immunohistochemistry and Western blot analysis. In order to gain more information on the functional importance of COX-1 and COX-2 in dermal wound healing, we analysed COX-1 and COX-2 protein levels using the Western blotting technique. In addition, we used immunohistochemistry to determine the cellular localization of the protein products. The collected skins were rapidly frozen and kept at -70degrees Cuntil assayed. Each frozen skin was lysed with 0.5 ml of ice-cold solution. Large tissue debris and nuclear fragments were removed by two low-speed centrifugations and the resulting supernatant fraction was used for blots. The skin extracts were stored below -20degrees Cfor further experiments. By Western blotting, compared to the activity of COX-2 in normal skin, its activity was increased at days 1, 4, 8, and 12 and was maximal at 1 day after incisional wound of mouse skin whereas COX-1 was barely detectable. In normal skin, COX-1 immunostaining was observed among the basal cells of epidermis whereas COX-2 immunostaining was detected in the more differentiated, suprabasal keratinocytes. At post-incision 1-4 days, COX-2 staining was particularly prominent in the inflammatory cells, and at day 8, many macrophage-like cells were stained positively. COX-2 immunoreactive fibroblast, macrophage-like cells, and newly formed vascular endothelial cells were increased in number at 12 days after incision. These data suggest that COX-2 is constitutively expressed, just as is COX-1, in epidermis and is associated with keratinocyte differentiation. In addition, these findings support the well-established role for COX-2, the prostaglandins that they generate, as mediators of inflammatory response.