Structural pathology in a rodent model of osteoarthritis is associated with neuropathic pain: increased expression of ATF-3 and pharmacological characterisation.

Abstract Intra-articular injection of mono-iodoacetate (MIA) in the rat knee joint induces a histopathology with similarities to osteoarthritis (OA). Typically, a synovitis (days 1–3) is observed followed by thinning of articular cartilage and subsequent lesion of subchondral bone at days 8–14 onwards. Behaviourally, weight-bearing asymmetry is observed, which is sensitive to anti-inflammatory pharmacology at early but not later (days 14+) time points. As subchondral bone is densely innervated, an intriguing possibility is that focal bone pathology may cause neuropathy in this model. In male Wistar rats, activating transcription factor (ATF)-3-immunofluorescence was used as a marker of nerve injury in lumber (L)4 and L5 dorsal root ganglia of the ipsilateral knee. Significantly increased ATF-3-immunoreactivity following MIA treatment was measured in L5 on days 8 and 14 ( P U -test), compared to saline controls. Furthermore, in an additional study animals were orally dosed vehicle (5 ml/kg), naproxen (0.3–10 mg/kg), celecoxib (1–10 mg/kg), amitriptyline (3–30 mg/kg) and gabapentin (10–100 mg/kg) and evaluated for weight-bearing asymmetry on days 14, 21 and 28 post-MIA. Significant resolution of weight-bearing was observed at high and intermediate doses of amitriptyline and gabapentin at all time points ( P