Comparison of Antinociceptive Effect of Pre- versus Post-treatment with Intrathecal Magnesium on the Formalin Test in Rats

Kang, Seong Sik; Huh, Jin; Son, Hee Jeong

Abstract

BACKGROUND
It is known that spinal N-methyl-D-aspartate (NMDA) receptors are involved in the changes seen during the second phase of the formalin test, and in vitro studies have shown that magnesium can cause voltage-dependent blockade of NMDA receptor channels in the neurons of the spinal dorsal horn. The purpose of this study was to evaluate the preemptive effect of intrathecal magnesium, and compare the behavioral antinociceptive responses, between pre-versus and post-formalin magnesium administrations in a rat pain model. METHODS: Male Sprague-Dawley rats (250-300 g) were implanted with lumbar intrathecal catheters, in order to receive, either saline (control), or magnesium. The formalin test was performed with 100microliter of 5% formalin. Rats received magnesium, 400microgram, intrathecally, through a catheter, either 10 minutes before, or 7 minutes after, the formalin test. The control (n = 8), pretreatment (n = 8) and post-treatment (n = 8) groups were studied. The pain related behavior was quantified by counting the incidence of flinches and the licking time of the injected hind paw, during phase 1 (1-6 min) and phase 2 (10-60 min), after the formalin injections. RESULTS: The intrathecal formalin injections produced a biphasic response of pain related behaviors in the three groups. In the pre- and post treatment groups, the rats showed less remarkable phase 2 responses than the control group (P < 0.05). However, there were no differences in the responses between the pre- and post treatment groups. The phase 1 responses showed no differences between the three groups. CONCLUSIONS: Intrathecal magnesium (400microgram) was effective on the inhibition of phase 2 nociceptive behaviors following the formalin injection. These results suggest that intrathecal administration of magnesium sulfate may be useful for patients with tonic pain involving the spinal NMDA receptors. However, a preemptive effect of the intrathecal magnesium was not observed.