Rat exposure in mice with neuropathic pain induces fear and antinociception that is not reversed by 5-HT2C receptor activation in the dorsal periaqueductal gray

Abstract

Previous studies have demonstrated that serotonin 5-HT2C receptors in the dorsal periaqueductal gray (dPAG) mediate both anxiety and antinociception in mice submitted to the elevated plus maze. The present study examined the effects of intra-dPAG infusion of the serotonin 5-HT2C receptor agonist (MK-212) in the defensive reactions and antinociception in mice with neurophatic pain confronted by a predator. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve, and predator confrontation was performed using the rat exposure test (RET). Our results demonstrated that both sham-operated and CCI mice exhibited intense defensive reactions when confronted by rats. However, rat-exposed CCI mice showed reduced pain reactivity in comparison to CCI mice exposed to a toy rat. Intra-dPAG infusion of MK-212 prior to predator exposure did not significantly alter defensive or antinociceptive responses. To our knowledge, our results represent the first evidence of RET-induced antinociception in mice. Moreover, the results of the present study suggest that 5-HT2C receptor activation in the dPAG is not critically involved in the control of predator-evoked fearful or antinociceptive responses.

Interplay between 5-HT2C and 5-HT1A receptors in the dorsal periaqueductal gray in the modulation of fear-induced antinociception in mice

“…The involvement of the PAG 5-HT 2C receptors in the modulation of pain response has been previously emphasized (Baptista-de-Souza et al, 2014;de Freitas et al, 2014;Furuya-da-Cunha et al, 2016;Obata et al, 2007). Thus, aiming to better characterize the role of the dPAG 5-HT 2C receptor in the modulation of OAA, we injected 0.1 nmol of SB 242084 (a dose without intrinsic effects on nociceptive response; see results of Exp.…”

Chronic Fluoxetine Impairs the Effects of 5-HT1A and 5-HT2C Receptors Activation in the PAG and Amygdala on Antinociception Induced by Aversive Situation in Mice

“…In this context, many studies have demonstrated that the analgesia induced by stimulation of the PAG is related to areas with a high concentration of serotonergic receptors (Lohof et al, 1987;Coimbra and Brandao, 1997;Brandao et al, 1999;Zhang et al, 2000;Lu et al, 2010). In this sense, we have previously reported the role of 5-HT 1A and 5-HT 2C receptors in reverse and accentuate, respectively, the fear-induced antinociception in mice (Baptista et al, 2012;Furuya-da-Cunha et al, 2016;Tavares et al, 2018).…”

“…These results suggest that (i) 5-HT may facilitate nociception INTRODUCTION Serotonin (5-HT) is involved in the etiology of numerous disease states, including depression, anxiety, panic disorders and painful conditions (Richardson, 1990;Supornsilpchai et al, 2006;Artigas, 2013a;Zangrossi and Graeff, 2014). The 5-HT receptors belong to the G-protein-coupled receptor superfamily (except for the 5-HT3 receptor, which is a ligand-gated ion channel) with at least 14 distinct members (Hoyer et al, 2002), however, the role of 5-HT 1A and 5-HT 2C receptor subtypes in the modulation of emotional and pain responses have been more extensively studied (Zanoveli et al, 2010;Strauss et al, 2013;Baptista-de-Souza et al, 2014;Furuya-da-Cunha et al, 2016).…”

Possible Involvement of Serotonergic Mechanism(s) in the Antinociceptive Effects of kaempferol

“…The effects of 5-HT1 receptors on the modulation of nociception have been widely studied [43,44]; however, it is required to obtain exact data on the antinociceptive activities of 5-HT2 areas [34]. Nonetheless, 5-HT2 receptors are possibly involved in the antinociceptive impacts of periaqueductal grey stimulation and stress [45].…”