Intrathecal administration of an NMDA or a non-NMDA receptor antagonist reduces mechanical but not thermal allodynia in a rodent model of chronic central pain after spinal cord injury

Spinal cord injuries (SCI) result in a devastating loss of function and chr onic central pain syndromes frequently develop in the majority of these pat ients. The present study uses a rodent spinal hemisection model of SCI in w hich mechanical and thermal allodynia develops by 24 days after injury. Pos t-operative paw withdrawal responses to low threshold and high threshold me chanical stimuli compared to pip-operative responses (4.78, 9.96, and 49.9 mN) were increased and were statistically significant (p < 0.05) for both f orelimbs and hindlimbs indicating the development of mechanical allodynia. By contrast, post-operatively, the temperature at which paw withdrawal acco mpanied by paw lick occurred was significantly decreased (p < 0.05), indica ting the development of thermal allodynia. The intrathecal application of e ither D-AP5, a competitive NMDA receptor antagonist, or NBQX-disodium salt, a competitive non-NMDA AMPA/kainate receptor antagonist, alleviated the me chanical allodynia and lowered the threshold of response for the high thres hold mechanical stimuli in a dose-dependent manner, and these decreases wer e statistically significant (p < 0.05). By contrast, neither the D-AP5 nor the NBQX produced a statistically significant change in the thermal allodyn ia behavior in either forelimbs or hindlimbs in the hemisected group. No si gnificant changes in locomotion scores. and thus no sedation, were demonstr ated by the hemisected group for the doses tested. These data support the p otential efficacy of competitive excitatory amino acid receptor antagonists in the treatment of chronic central pain. particularly where input from lo w threshold mechanical afferents trigger the onset of the painful sensation . Furthermore. these data suggest a role for both NMDA and non-NMDA recepto rs in the development of plastic changes in the spinal cord that provide th e underlying mechanisms for central neuropathic pain. (C) 2000 Elsevier Sci ence B.V. All rights reserved.