Behavioral characterization and effect of clinical drugs in a rat model of pain following spinal cord compression

Abstract

Chronic pain symptoms, including spontaneous unevoked pain and evoked cutaneous hypersensitivity, appear following spinal cord injury (SCI). A reliable preclinical model is needed to develop effective analgesic treatments for these symptoms. A previously described rat model of SCI pain was modified and behaviorally characterized and used to test clinically available drugs. A segment of the mid-thoracic spinal cord was compressed for 60 s with a micro-vascular clip. The sensitivity of the hind paws to noxious heat (Hargreaves test), innocuous tactile (von Frey filaments), and cooling (acetone) stimuli were determined once per week beginning 1 week following spinal compression. Spinal cord compression led to long lasting hypersensitivity to stimuli, lasting for at least 12 weeks post-surgery. Systemic baclofen, gabapentin, tramadol, and morphine dose-dependently attenuated tactile hypersensitivity. No effect on tactile hypersensitivity was observed with amitriptyline, carbamazepine, rofecoxib, and diazepam. Baclofen and morphine also dose-dependently ameliorated heat hypersensitivity. In contrast, no effect on heat hypersensitivity was observed with amitriptyline, carbamazepine, diazepam and gabapentin. The current data suggest that the model can potentially differentiate those drugs with analgesic efficacy from those that do not have efficacy in SCI pain. Thus, the model may be useful for rapid screening and clinical translation of promising SCI pain therapies.