Differential analgesic effects of morphine and gabapentin on behavioural measures of pain and disability in a model of osteoarthritis pain in rats

Osteoarthritis (OA) is associated with chronic debilitating joint pain. Pain is the result of an emotional and sensory experience and preclinical models of OA can thus be useful to better understand the underlying mechanisms of the disease and test new therapeutic options. We induced unilateral knee CA in Sprague-Dawley rats using monosodium iodoacetate (MIA), a glycolysis inhibitor and assessed the effects of acute and chronic morphine and gabapentin using a battery of quantitative behavioural outcome measures of pain and disability. Animals received a single intra-articular injection of 2 mg MIA in 25 mu l saline, causing inflammation and progressive cartilage degradation. Mechanical and thermal sensitivity as well as ambulatory-evoked pain were then monitored using von Frey hairs, acetone and a rotarod. Once maximum nociceptive responses were reached, chronic bi-daily morphine (3 mg/kg s.c.) or gabapentin (30 mg/kg s.c.) were administered for 5 days. We observed a marked biphasic mechanical hypersensitivity that increased and reached a plateau from day 14 (317.6% of control response, p < 0.01, with von Frey 6 g). Moreover we found a marked cooling hypersensitivity, and validated a novel ambulatory-evoked pain score. These measures were significantly reduced after both acute (13.3% of sham response, p < 0.01, von Frey 6 g) and chronic (38.3%, p < 0.05) morphine whilst only chronic gabapentin (37.0%, p < 0.05) had an effect. We show the reliability of the model in terms of mechanical hypersensitivity and demonstrate cooling hypersensitivity and ambulatory-evoked pain. In terms of translational research, the effects of morphine and gabapentin validate the model and suggest trials of these therapeutic approaches in OA patients. Crown Copyright (C) 2008 Published by Elsevier Ltd. on behalf of European Federation of Chapters of the International Association for the Study of Pain. All rights reserved.