Amitriptyline prevents thermal hyperalgesia and modifications in rat spinal cord GABAB receptor expression and function in an animal model of neuropathic pain

Using an animal model of neuropathic pain, behavioral and biochemical experiments were performed to assess the effects of this condition on pain threshold and GABAB receptor sensitivity and subunit gene expression in the rat lumbar spinal cord. The results indicate that partial sciatic nerve ligation decreases thermal and mechanical pain withdrawal latencies, and increases baclofen-stimulated [35S]GTPγS binding and GABAB receptor subunit gene expression in the rat lumbar spinal cord, suggesting that neuropathic pain may be due, in part, to a deficiency in GABAergic transmission. The experiments also demonstrate that daily administration (10 mg/kg, i.p.) of amitriptyline, a tricyclic antidepressant used for the treatment of neuropathic pain, for 1 week after surgery prevents the decline in thermal pain threshold, the increase in GABAB(2) gene expression, and development of increased GABAB receptor function in spinal cord resulting from nerve damage. These findings indicate that the efficacy of amitriptyline as a treatment for neuropathic pain may be related to an ability to maintain spinal cord GABAB receptor activity.