Antinociceptive effect following dietary-induced thiamine deficiency in mice - Involvement of substance P and somatostatin

We produced thiamine deficiency by treating mice with a thiamine deficient (TD) diet, but not with pyrithiamine, a thiamine antagonist. Twenty days af ter TD feeding, a significant antinociceptive effect was observed in the fo rmalin test. A single injection of thiamine HCl (50 mg/kg, s.c.) on the 19t h day after TD feeding (on the late TD stage) failed to reverse the antinoc iceptive effect, the muricide effect, and impairment of avoidance learning induced by TD feeding, as compared to pair-fed controls. These results indi cate the possibility that the TD-induced antinociceptive effect may result from irreversible changes in the spinal and/or brain neurons. To clarify th e involvement of substance P (SP) and somatostatin (SST) systems in the spi nal cord, we examined the effect of intrathecal (i.t.) injections of these agonists on TD feeding-inducd elevation of pain threshold. I.t. injection o f SP and SST elicited a behavioral response consisting of reciprocal hindli mb scratching, biting and/or licking of hindpaws. There was no significant difference in the behavioral response to SP between TD mice and PF mice on the 5th day after feeding. However, on the 10th and 20th day after TD feedi ng the response to SP was significantly increased compared with PF mice. Th is phenomenon was also observed with SST on the 20th day after TD feeding. These results indicate the possibility that TD feeding may produce an incre ased behavioral response to SP and SST through an enhanced sensitivity of n eurokinin-1 and SST receptors in the spinal cord. Taken together, the antin ociceptive effect following TD feeding may result from a decrease in spinal SP and SST contents. (C) 2001 Elsevier Science Inc. All rights reserved.