Retrosplenial cortex reduces hyperalgesia in neuropathic pain in rats.

Glaucia Melo Reis, Ana Carolina Rossaneis, Karina Genaro Borelli, Wiliam Alves Prado. Faculty of Medicine of Ribeirao Preto / University of Sao Paulo, Pharmacology 14091190, Brazil

Background and aims: In previews studies we showed for the first time that electrical stimulation of, or the injection of glutamate into the retrosplenial cortex (RSC) induces antinociception in the rat tail flick test and formalin tests (Reis et al., 2010) and reduces incision pain (Rossaneis et al., 2011). In addition, this effect against the tail-flick test is not due to changes in motor performance or to a nonspecific postictal analgesic phenomenon and stimulating the RSC against the tail-flick reflex do not occur in rats with bilateral lesions of the DLF (Reis et al., 2010). However, still have not evidence of RSC participation in chronic pain resulting from nerve injury. Thus, this study aims to evaluate the possible role in RSC in induction and maintenance of neuropathic pain. Methods: The experiments were conducted in accordance with the Ethical Committee for Animal Experimentation of the Faculty of Medicine of Ribeirao Preto/USP (No. 159/ 2007). The rats (male Wistar, 140-160g) were submitted to stereotactic implantation of guide cannula directed at the RSC. After five days were measured baseline paw withdrawal thresholds to mechanical stimulation using electronic algesymeter (von Frey Test). The animals were then submitted to a variation of the model of sciatic nerve ligation. In the 2° and 7° days after ligation, were measured paw withdrawal thresholds before and 15 minutes after microinjection of lidocaine 2% (0.25µl). The PWT were considered in terms of force (in grams) required to evoke the reflex paw withdrawal. Thresholds in each subgroup were analyzed and presented in graphs as mean ± standard error of mean (SEM). The subgroups were compared using analysis of variance (MANOVA).The factors analyzed were treatments, time and treatment-timeinteraction. For each time, was performed analysis of variance (one-way) followed by Bonferroni test with significance set at P <0.05 in all cases. Results: The RSC neural blockade significantly accentuated the mechanical allodynia induced by ligation of the sciatic nerve in both 2° and 7°day. The curves were differ significantly regarding treatment (F3,20 = 92.0 and 41.90) ; time (F10,200 = 322.20 and 410) and had significant treatment x time interaction (F30,200 = 46.37 and 92.97; P < 0.0001 in all cases). This effect was more intense in induction phase. Conclusions: Our results suggest the involvement of the RSC in descending inhibitory modulation of neuropathic pain induced by sciatic nerve ligation in rats. However, this modulation appears to more intense the induction than maintenance phase of the neuropathy.

References:

Reis GM, Dias QM, Silveira JWS, Del Vecchio F, Garcia-Cairasco N, Prado WA. J.Pain 2010;11:1015-26.

Rossaneis, A.C; Reis, G.M.; Prado, W.A. Pharmacol. Bioch. Behav. 2011; 2: 220-7. Financial Support: Fapesp.