5-HT₃ receptor within the amygdaloid complex modulates pain hypersensitivity induced by empathy model of cohabitation with a partner in chronic pain condition in mice

ABSTRACT

Cohabitation with a partner undergoing chronic pain induces pain hypersensitivity. Among a lot of other neurochemical pathways, the serotonin (5-HT) role, specifically the 5-HT₃ receptor (5-HT₃R), in the amygdala has never been evaluated in this model. Here we studied the effects of the amygdala’s chemical inhibition, its neuronal activation pattern, and 5-HT, 5-HIAA, and 5-HT turnover within the amygdala. Furthermore, the systemic and intra-amygdala 5-HT₃R activation and blockade in mice that cohabited with a conspecific subjected to chronic constriction injury were investigated. Male Swiss mice were housed in partners for 28 days. The dyads were divided into two groups on the 14^th day: cagemate nerve constriction (CNC) and cagemate sham (CS). On the 24^th day, cagemates underwent a stereotaxic surgery (when necessary) and, on the 28^th day, they were evaluated on the writhing test. The amygdala inactivation promotes pain-hypersensitivity behaviors in groups and dyads; cohabitation with a partner with chronic pain did not change FosB-labeled cells in the amygdala’s nucleus and increases 5-HT turnover in cagemates. Systemic and intra-amygdala 5-HT₃R activation attenuated and enhanced the number of writhes, respectively. In contrast, 5-HT₃R blockade reduced hypersensitivity pain response. Results suggest the involvement of amygdala serotonergic signaling via 5-HT₃R in empathy-like behavior.

KEYWORDS:

• Empathy
• amygdala
• serotonin
• 5-HT₃ receptors
• pain hypersensitivity 22 July 2021

Acknowledgments

The experiments described in this manuscript were funded by CNPq, Brazil 482356/2013-8), CAPES Brazil (financing code 001), and FAPESP (2017/25409-0), Brazil. L. R. R. Tavares received a scholarship from CNPq, Brazil (153163/2016-0). V. Pelarin, D. P. Ferrari, and D. Baptista-de-Souza received a scholarship from FAPESP (2012/22238-6; 15/15335-3; 2015/0004-6). Ricardo L. Nunes-de-Souza and A. Canto-de-Souza received a research fellowship from CNPq, Brazil (306556/2015-4; 309201/2015-2). The authors would like to thank Lara Maria Silveira for her technical assistance.

Disclosure statement

No potential conflict of interest was reported by the author(s).

Additional information

Funding

This work was supported by the CAPES [CAPES, financing code 001]; CNPq [306556/2015-4, 309201/2015-2,482356/2013-8, 153163/2016-0]; Fundação de Amparo à Pesquisa do Estado de São Paulo [15/15335-3; 2015/0004-6,2017/25409-0, 2012/22238-6].