Strychninemdependent alladynia in the urethanemanesthetized

The blockade of spin& glycine receptors with intrathecal strychnine produces a reversible allodynia-like state in the rat. Thus, hair deflection, in the presence of intrahecal strychmine, induces cardiovascular and motor withdrawal responses comparable with those evoked by noxious thermal, mechanical, or chemical stimulation in the absence of strychnine. Bn the present study, we mapped the cutaneous sites of abnormal sensitivity to hair deflection throughout the strychnine time course to investigate the segmental distribution of strychnine-induced allodynia. The ability of intrathecal glycine and the glycine derivative betaine to reverse strychnine-induced allodynia was also determined using dose-response analysis. Following intrathecal strychnine (40 pg), stroking the legs, flanks, lower back, and tail with a cotton-tipped applicator evoked a pronounced increase in mean arterial pressure, tachycardia, and an abmgt motor withdrawal response in urethane-anesthetized rats. These abnormal responses were only evoked by hair deflection at discrete sites, corresponding to the cutaneous dematomes innervated by spinal segments near the site of strychnine injection. In rats with intrathecal catheters lying laterally in the subarachnoid space, allodynic sites were observed unilaterally on the ipsilateral side of intrathecal strychnine injection. Recoveq from strychnine was complete by 30 min in all affected dermatomes. The cardiovascular and motor withdrawal responses to hair deflection were dose dependently inhibited by intrathecal glycine and intrathecal betaine. The ED,, (95 76 confidence interval) for intrathecal glycine was 669 (429 865) yg for the heart rate response, 694 (548 878) pg for the pressor response, and 549 (458-658) yg for the motor withdrawal response. The corresponding values for intrathecal betaine were 981 (509 1889)' 1045 (740 1476)' and 1083 (843 1391) pg, respectively. There was no difference in the effect of betaine on sensory-evoked cardiovascular and motor responses. Cortical electroencephalogra#ic activity was not affected by intrathecal glycine or beiaine, consistent with a spinal locus of action in reversing strychnine-induced allodynia. These results support the hypothesis that removal of spinal glycinergic modulation from low threshold afferent input with intrathecal strychnine results in segmentally localized, tactile-evoked dlsdynia.