Figure 1.

Overview of experimental timeline: The effect of pre-exposure to morphine on OA-like pain behavior. (A) Study 1: Female SD rats received bi-daily dosing with systemic morphine (3 mg/kg, s.c.) or saline for 1 week before intra-articular injection of 2 mg MIA or saline. Systemic treatment with saline or morphine continued for a further 2 weeks. Pain behavior was assessed 1 hour before and after morning injection of morphine or saline to provide measures of both chronic and acute effects of treatment. (B) Study 2: Female SD rats received bi-daily dosing with systemic morphine (3 mg/kg, s.c.) or saline for 1 week before intra-articular injection of 2 mg MIA or saline. Systemic treatment with saline or morphine continued for a further 3 weeks (n = 6/group/study: saline/saline, saline/MIA, morphine/saline, and saline/MIA). To focus on the chronic effects of morphine, behavioral assessments were made 1 hour before the first dose each morning. MIA, monosodium iodoacetate; OA, osteoarthritis; PWTs, paw withdrawal thresholds; s.c., subcutaneous; SD, Sprague-Dawley; WB, weight-bearing.