Involvement of Pain Associated Anxiety in the Development of Morphine Tolerance in Formalin Treated Mice

The Japanese Journal of Pharmacology

Masakatsu Takahashi¹  Hiroshi Kaneto¹  A.F.M. Mohibur Rahman¹ 

[1] Department of Pharmacology, Faculty of Pharmaceutical Sciences, Nagasaki University

关键词: Chronic pain;    Formalin;    Anti-inflammatory drug;    Morphine tolerance;    Anxiety;   

DOI  :  10.1254/jjp.65.313

学科分类：药理学

来源: Nihon Yakuri Gakkai Henshuubu / Japanese Pharmacological Society

【 摘 要 】

References(20)Cited-By(13)ABSTRACT-The mechanism underlying the previous findings that the development of antinociceptive tolerance to morphine was significantly delayed in the presence of inflammatory pain induced by formalin was examined. Measurements of the pain threshold at different time intervals have shown that pain lasts around one week in the formalin treated mice. A single dose of indomethacin (10 mg/kg) or aspirin (400 mg/kg), 30 min before formalin injection, and daily 400 mg/kg of aspirin had no effects on the pain threshold or swelling, and it also did not affect the delay of morphine tolerance development. Daily administration of diazepam, 1 mg/kg, 1 hr before morphine injection completely abolished the delay. This effect was antagonized by 2 mg/kg of flumazenil, administered 15 min before diazepam injection. These results suggest that pain-associated anxiety participates in the delay of morphine tolerance development and consequently the benzodiazepine-receptor complex plays a role in the development of morphine tolerance during a painful state.

【 授权许可】

Unknown