Intrathecal Strychnine but not Bicuculline Antagonizes Spinal Cord Stimulation-Produced Inhibition of Heat-Evoked and "Allodynia-like" Responses in Rats

Academic Article


  • Introduction. Electrical stimulation of the spinal cord using an epidural or intrathecal stimulating electrode will inhibit the tail flick response of halothane-anesthetized rats to radiant heat. The present study examined the effects of the GABA-antagonist bicuculline and the glycine-antagonist strychnine on this inhibition. These drugs have also been noted to produce "allodynia-like" responses, motor movements elicited by nonnoxious cutaneous stimuli (1). The effect of spinal cord stimulation on these responses was also evaluated. Methods. Male, Sprague-Dawley rats were deeply anesthetized with halothane (2-5% inhaled with oxygen). The trachea was cannulated and rats artificially ventilated. A catheter (PE10 tubing) was introduced into the intrathecal space of the lumbar enlargement using the method of Yaksh and Rudy (2). At the same time, an additional PE10 tubing containing a fine silver wire electrode was inserted in the intrathecal space and positioned at a lower cervical level. A grounding electrode was placed in the cervical musculature and wound margins closed. The halothane concentration was reduced to 0.6-0.8% and the tail flick reflex was evoked by radiant heating of the ventral tail. Spinal cord stimulation (SCS) consisting of 100 Hz squarewave cathodal pulses of 0.4 ms duration was applied. The minimal stimulation current (in 25 juA increments) which inhibited the tail flick reflex to a latency greater than 8 seconds on three consecutive trials was defined as the SCS-threshold. Rats then received intrathecal injections of normal saline or cumulative doses of bicuculline (1 and 10 ^ig) or strychnine (5, 10 and 50 ng). The SCS-threshold was then redetermined. Responses to brushing of the tail with a cotton-tipped applicator were similarly determined in the presence and absence of SCS. Results. SCS reliably inhibited the tail flick reflex prior to intrathecal drug administration. Motor responses to brushing of the tail were not evoked in any rats prior to intrathecal drug administration, but were vigorous in the bicuculline and strychnine-treated rats. The SCS-threshold was unaffected in the saline or bicuculline-treated rats, but was significantly increased in rats treated with intrathecal strychnine. At the highest dose of strychnine, the tail flick reflex could not be reliably evoked and SCS produced significant motor effects. SCS inhibited the responses to brushing of the tail at thresholds similar to those needed to inhibit responses to tail heating. At the highest dose of strychnine, motor responses to brushing of the tail were not blocked by SCS. Discussion. These results suggest that SCS-produced inhibition of motor responses to noxious and non-noxious stimuli are mediated by a glycinergic mechanism. References.
  • Author List

  • Ness TJ
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  • 22
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  • 2 SUPPL.