caa a22 4500 445372761 CHVBK 20180317142952.0 cr unu---uuuuu 170323e20110201xx s 000 0 eng 10.1007/s00540-010-1046-7 doi (NATIONALLICENCE)springer-10.1007/s00540-010-1046-7 Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation [Elektronische Daten] [Tatsushige Iwamoto, Yoshihiro Takasugi, Hideaki Higashino, Hiroyuki Ito, Yoshihisa Koga, Shinichi Nakao] Purpose: Systemic carbamazepine, a voltage-gated sodium channel blocker, has been reported to dose-dependently reduce inflammatory hyperalgesia. However, the antinociceptive effects of carbamazepine on the spinal cord in inflammatory conditions are unclear. The aim of the present study was to evaluate the antinociceptive effects of carbamazepine on the spinal cord in a chronic inflammatory condition. Methods: In Sprague-Dawley rats, a chronic inflammatory condition was induced by complete Freund's adjuvant (CFA) inoculation into the tail. Tail flick (TF) latencies were measured following intraperitoneal carbamazepine, or intrathecal carbamazepine or tetrodotoxin injection in intact rats and in the chronic inflammatory rats. From the values of TF latency at 60min after drug injection, the effective dose required to produce 50% response (ED50) of each drug was derived. Results: Carbamazepine attenuated thermal responses with both systemic and intrathecal administration. The effect was more evident in rats with chronic inflammation than in intact rats; the ED50s of intraperitoneal carbamazepine in intact and inflamed rats were 12.39 and 1.54mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED50s of 1.006pmol in intact rats and 0.310pmol in inflamed rats. The relative potencies of intrathecal carbamazepine versus tetrodotoxin for inhibition were approximately 1:150-1:300 in intact and inflamed rats. Conclusion: These results indicate that the inhibition of voltage-gated sodium channels, at least tetrodotoxin-sensitive channels, may contribute to the antinociceptive effect of carbamazepine on CFA-induced inflammatory pain, since lower doses of intrathecal carbamazepine and tetrodotoxin attenuated thermal responses to a greater extent in inflamed rats than in intact rats. Japanese Society of Anesthesiologists, 2010 Chronic inflammatory pain nationallicence Voltage-gated sodium channel nationallicence Carbamazepine nationallicence Tetrodotoxin nationallicence Complete Freund's adjuvant nationallicence Iwamoto Tatsushige Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut Takasugi Yoshihiro Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut Higashino Hideaki Department of Pharmacology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut Ito Hiroyuki Department of Pathology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut Koga Yoshihisa Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut Nakao Shinichi Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut Journal of Anesthesia Springer Japan 25/1(2011-02-01), 78-86 0913-8668 25:1<78 2011 25 540 https://doi.org/10.1007/s00540-010-1046-7 text/html Onlinezugriff via DOI 1 research-article jats NATIONALLICENCE 856 40 https://doi.org/10.1007/s00540-010-1046-7 text/html Onlinezugriff via DOI NATIONALLICENCE 700 1- Iwamoto Tatsushige Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut NATIONALLICENCE 700 1- Takasugi Yoshihiro Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut NATIONALLICENCE 700 1- Higashino Hideaki Department of Pharmacology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut NATIONALLICENCE 700 1- Ito Hiroyuki Department of Pathology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut NATIONALLICENCE 700 1- Koga Yoshihisa Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut NATIONALLICENCE 700 1- Nakao Shinichi Department of Anesthesiology, Kinki University Faculty of Medicine, 377-2 Ohno-higashi, 589-8511, Osaka-sayama, Osaka, Japan aut NATIONALLICENCE 773 0- Journal of Anesthesia Springer Japan 25/1(2011-02-01), 78-86 0913-8668 25:1<78 2011 25 540 Metadata rights reserved Springer special CC-BY-NC licence nationallicence BK010053 XK010053 XK010000 NATIONALLICENCE NATIONALLICENCE NL-springer