Open AccessInvolvement of Pain Associated Anxiety in the Development of Morphine Tolerance in Formalin Treated Mice
Author(s) -
A.F.M. Mohibur Rahman,
Masakatsu Takahashi,
Hiroshi Kojima
Publication year - 1994
Publication title -
japanese journal of pharmacology/japanese journal of pharmacology
Language(s) - English
Resource type - Journals
eISSN - 1347-3506
pISSN - 0021-5198
DOI - 10.1254/jjp.65.313
Subject(s) - morphine , diazepam , flumazenil , nociception , medicine , aspirin , anesthesia , pharmacology , pain tolerance , anxiety , threshold of pain , benzodiazepine , receptor , psychiatry
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.