Comparative Efficacy of GABAA and GABAB Receptor Agonists in Pain Alleviation in a Spinal Cord Injury Model of Neuropathic Pain

Abstract

We investigated the effectiveness of intrathecal introduction of GABAA and GABAB receptor agonists in reversing pain modalities in a central model of neuropathic pain. In adult male Wistar rats, spinal cord injury was produced by compression of the spinal cord at the T6–T8 level. For drug delivery to the spinal cord, a PE10 catheter was inserted into the subarachnoid space through an intervertebral foramen. Testing was performed three weeks after spinal cord injury. Mechanical and thermal hyperalgesia were estimated using the pressure withdrawal (Randall–Selitto) and heat withdrawal (Hargreaves) tests, respectively. Tactile allodynia was quantitated by testing with the von Frey filaments. Cold allodynia was assessed by the acetone drop test to the hindpaw. The motor function was evaluated using the 21-score scale for locomotion in the open field. At the end of the experiment, animals were anesthetized and transcardially perfused with fixative, and sections of the spinal cord were prepared and stained. Compression injury of the spinal cord produced a cavity in the dorsal horn of the spinal cord and resulted in clear impairment of the motor function of animals. Spinal administration of both abovementioned drugs reduced mechanical hyperalgesia and cold and tactile allodynia. The GABAA agonist muscimol also decreased thermal hyperalgesia, while the GABAB agonist baclofen did not change this phenomenon. Thus, exogenous administration of GABAA agonists can reverse all spinal cord compression-induced sensory disorders. These agents may provide a better therapy of neuropathic pain than GABAB agonists.