Neuropathic pain is a complex disorder associated with emotional and cognitive deficits that may impair nociceptive manifestations. There is high inter-individual variability in the manifestations of human neuropathic pain, which largely depends on personality traits. We aim to identify the influence of different behavioral traits in the interindividual vulnerability to neuropathic pain manifestations using behavioral, electrophysiological and genetic approaches. We first selected mice with extreme social and emotional traits and look for correlation with the spontaneous neuronal activity in the central amygdala. Neuropathic pain was induced to these mice to evaluate the influence of behavioral traits on nociceptive manifestations and gene expression profiles in the amygdala. Our results show an association of the spontaneous central amygdala neuronal activity with the sociability behavior. We demonstrate that low sociable, high anxious and low depressive phenotypes develop enhanced nociceptive hypersensitivity after nerve injury. However, greater emotional alterations and cognitive impairment are observed in high sociable, anxious-like and depressive-like mice, indicating that nociceptive, emotional and cognitive manifestations of neuropathic pain do not correlate with each other. Gene analyses identify high Pdyn and Il6 levels in the amygdala as indicative of enhanced nociceptive hypersensitivity and reveal an association between high Gadd45 expression and attenuated emotional and cognitive manifestations of neuropathic pain.

This work was supported by the European Commission, FP7 (#HEALTH-F2-2013- 602891), the Spanish Ministerio de Economía y Competitividad MINECO (#SAF2014-59648-P and #SAF2017-84060-R), the Spanish Instituto de Salud Carlos III, RETICS-RTA (#RD12/0028/0023) and the Generalitat de Catalunya, AGAUR (#2014-SGR-1547) and Polish Ministry of Science and Education (#3070/7.PR/2014/2). M.M.N. and R.N. are recipients of a predoctoral fellowship from the Spanish Ministerio de Educación, Cultura y Deporte (MECD). I.M.L.M. is recipient of a predoctoral fellowship from the Mexican Consejo Nacional de Ciencia y Tecnología (CONACyT). FEDER partial funding is also acknowledged. W.B. and A.B. are recipients of Polish Ministry of Science and Education and European Commission grants