Strychnine-dependent allodynia in the urethane-anesthetized rat is segmentally distributed and prevented by intrathecal glycine and betaine.
The blockade of spinal glycine receptors with intrathecal strychnine produces a reversible allodynia-like state in the rat. Thus, hair deflection, in the presence of intrathecal strychnine, induces cardiovascular and motor withdrawal responses comparable with those evoked by noxious thermal, mechanical, or chemical stimulation in the absence of strychnine. In 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 micrograms), stroking the legs, flanks, lower back, and tail with a cotton-tipped applicator evoked a pronounced increase in mean arterial pressure, tachycardia, and an abrupt motor withdrawal response in urethane-anesthetized rats. These abnormal responses were only evoked by hair deflection at discrete sites, corresponding to the cutaneous dermatomes 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. Recovery 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 ED50 (95% confidence interval) for intrathecal glycine was 609 (429-865) micrograms for the heart rate response, 694 (548-878) micrograms for the pressor response, and 549 (458-658) micrograms for the motor withdrawal response. The corresponding values for intrathecal betaine were 981 (509-1889), 1045 (740-1476), and 1083 (843-1391) micrograms, respectively. There was no difference in the effect of betaine on sensory-evoked cardiovascular and motor responses. Cortical electroencephalographic activity was not affected by intrathecal glycine or betaine, 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 allodynia.
Sherman
S E
SE
Division of Basic Medical Sciences, Memorial University of Newfoundland, St. John's, Canada.
Loomis
C W
CW
D018686:Anesthetics, Intravenous; D000818:Animals; D001622:Betaine / Q000008:administration & dosage / Q000494:pharmacology*; D005073:Evoked Potentials, Somatosensory / Q000187:drug effects; D005998:Glycine / Q000008:administration & dosage / Q000494:pharmacology*; D018684:Glycine Agents / Q000008:administration & dosage / Q000633:toxicity*; D007278:Injections, Spinal; D008297:Male; D010146:Pain / Q000139:chemically induced* / Q000503:physiopathology / Q000517:prevention & control*; D051381:Rats; D017207:Rats, Sprague-Dawley; D012867:Skin / Q000187:drug effects; D013331:Strychnine / Q000008:administration & dosage / Q000819:agonists / Q000633:toxicity*; D014520:Urethane
D018686:Anesthetics, Intravenous; D018684:Glycine Agents; D014520:Urethane; D001622:Betaine; D013331:Strychnine; D005998:Glycine