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Neural Regeneration Research 2013年第35期8卷 3325-3333页

作者： Xiuhong Yuan Xiangyan Liu Qiuping Tang Yunlong Deng Institute of Psychosomatic Health the Third Xiangya Hospital of Central South University

Approximately 50-70% of patients experience incision-induced mechanical nociception after sur- gery. However, the mechanism underlying incision-induced mechanical nociception is still unclear. Interleukin-10 and brain-derived neurotrophic factor are important pain mediators, but whether in- terleukin-10 and brain-derived neurotrophic factor are involved in incision-induced mechanical no- ciception remains uncertain. In this study, forty rats were divided randomly into the incision surgery （n = 32） and sham surgery （n = 8） groups. Plantar incision on the central part of left hind paw was performed under anesthesia in rats from the surgery group. Rats in the sham surgery group re- ceived anesthesia, but not an incision. Yon frey test results showed that, compared with the sham surgery group, incision surgery decreased the withdrawal threshold of rats at 0.5, 3, 6 and 24 hours after incision. Immunofluorescence staining in the dorsal root ganglia of the spinal cord （L3-5） showed that interleukin-10 and brain-derived neurotrophic factor were expressed mainly on small- and medium-sized neurons （diameter 〈 20 pm and 20-40 pm） and satellite cells in the dorsal root ganglia of the spinal cord （L3-5） in the sham surgery group. By contrast, in the surgery group, high expression of interleukin-10 and brain-derived neurotrophic factor appeared in large-sized neurons （diameter 〉 40 pm） at 6 and 24 hours after incision surgery, which corresponded to the decreased mechanical withdrawal threshold of rats in the surgery group. These experimental findings suggest that expression pattern shift of interleukin-10 and brain-derived neurotrophic factor induced by inci- sion surgery in dorsal root ganglia of rats was closely involved in lowering the threshold to me- chanical stimulus in the hind paw following incision surgery. Pain-related mediators induced by in- cision surgery in dorsal root ganglia of rats possibly underlie mechanical nociception in ipsilateral hind paws.

关键词： neural regeneration peripheral nerve injury interleukin-lO brain-derived neurotrophic factor rats mechanical nociception dorsal root ganglia incision pain-related mediators von frey test hind paws grants-supported paper neuroregeneration

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In Vivo Interaction of Morphine and Diclofenac

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Pharmacology & Pharmacy 2016年第12期7卷 493-503页

作者： Yoshiaki Kimura Koki Muryoi Mika Shibata Noriyuki Ozaki Kunizo Arai Faculty of Pharmacy Institute of Medical Pharmaceutical and Health Sciences Kanazawa University Kanazawa Japan Suisen Pharmacy Fukui Pharmaceutical Association Fukui Japan Department of Functional Anatomy Graduate School of Medical Sciences Kanazawa University Kanazawa Japan

The number of studies on possible pharmacokinetic interactions between opioid analgesics and nonsteroidal anti-inflammatory drugs (NSAIDs), which are commonly used in combination for the treatment of chronic pain, is limited. In rats, the major metabolic pathway of morphine is glucuronidation to morphine-3-glucuronide (M3G) by UDP-glucuronosyltransferase. In this study, we investigated the influence of diclofenac (NSAID) on the formation of M3G in vitro using rat liver tissue homogenates. Competitive inhibition of M3G formation by diclofenac was observed with an average Ki of 19.9 μM. Because these in vitro findings suggested that a pharmacokinetic interaction occurs in vitro , we investigated whether diclofenac inhibits the glucuronidation of morphine in rats. A single dose of diclofenac increased serum concentrations of both morphine and M3G and showed a higher analgesic efficacy in the von frey test. Furthermore, diclofenac caused a net decrease in morphine urine concentrations, but the excretion of M3G through biliary and urinary routes was unchanged. These results demonstrated that in contrast to in vitro data a single dose of diclofenac did not alter the glucuronidation of morphine in vitro .

关键词： Morphine Diclofenac Udp-Glucuronosyltransferase von frey test

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