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Journal of Anesthesia

, Volume 25, Issue 1, pp 78–86 | Cite as

Antinociceptive action of carbamazepine on thermal hypersensitive pain at spinal level in a rat model of adjuvant-induced chronic inflammation

  • Tatsushige Iwamoto
  • Yoshihiro Takasugi
  • Hideaki Higashino
  • Hiroyuki Ito
  • Yoshihisa Koga
  • Shinichi Nakao
Original Article

Abstract

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 60 min 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 1.54 mg/kg, and those of intrathecal carbamazepine were 0.311 and 0.048 nmol, respectively. Intrathecal tetrodotoxin also clearly inhibited the response, with ED50s of 1.006 pmol in intact rats and 0.310 pmol 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.

Keywords

Chronic inflammatory pain Voltage-gated sodium channel Carbamazepine Tetrodotoxin Complete Freund’s adjuvant 

Notes

Acknowledgments

This study was supported by The Osaka Medical Research Foundation for Incurable Diseases in 2009.

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Copyright information

© Japanese Society of Anesthesiologists 2010

Authors and Affiliations

  • Tatsushige Iwamoto
    • 1
  • Yoshihiro Takasugi
    • 1
  • Hideaki Higashino
    • 2
  • Hiroyuki Ito
    • 3
  • Yoshihisa Koga
    • 1
  • Shinichi Nakao
    • 1
  1. 1.Department of AnesthesiologyKinki University Faculty of MedicineOsaka-sayamaJapan
  2. 2.Department of PharmacologyKinki University Faculty of MedicineOsaka-sayamaJapan
  3. 3.Department of PathologyKinki University Faculty of MedicineOsaka-sayamaJapan

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