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Publication : Involvement of pain associated anxiety in the development of morphine tolerance in formalin treated mice.

First Author  Rahman AF Year  1994
Journal  Jpn J Pharmacol Volume  65
Issue  4 Pages  313-7
PubMed ID  7990268 Mgi Jnum  J:20515
Mgi Id  MGI:68602 Doi  10.1254/jjp.65.313
Citation  Rahman AF, et al. (1994) Involvement of pain associated anxiety in the development of morphine tolerance in formalin treated mice. Jpn J Pharmacol 65(4):313-7
abstractText  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.
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