Sigma-1 receptors control neuropathic pain and macrophage infiltration into the dorsal root ganglion after peripheral nerve injury Bravo Caparrós, Inmaculada Ruiz Cantero, María del Carmen Perazzoli, Gloria Cronin, SFJ Vela, José Miguel Hamed, MF Penninger, JM Baeyens Cabrera, José Manuel Cobos del Moral, Enrique José Nieto López, Francisco Rafael ATF3 CCL2 IL-6 Neuroinflammation Spared nerve injury Sigma-1 receptor Neuropathic pain Neuron-immune interaction in the dorsal root ganglia (DRG) plays a pivotal role in the neuropathic pain development after nerve injury. Sigma-1 receptor (Sig-1R) is expressed by DRG neurons but its role in neuropathic pain is not fully understood. We investigated the effect of peripheral Sig-1R on neuroinflammation in the DRG after spared (sciatic) nerve injury (SNI) in mice. Nerve injury induced a decrease in NeuN staining along with the nuclear eccentricity and ATF3 expression in the injured DRG. Sig-1R was present in all DRG neurons examined, and after SNI this receptor translocated to the periphery of the soma and the vicinity of the nucleus, especially in injured ATF3 + neurons. In WT mice, injured DRG produced the chemokine CCL2, and this was followed by massive infiltration of macrophages/monocytes, which clustered mainly around sensory neurons with translocated Sig-1R, accompanied by robust IL-6 increase and mechanical allodynia. In contrast, Sig-1R knockout (Sig-1R-KO) mice showed reduced levels of CCL2, decreased macrophage/monocyte infiltration into DRG, and less IL-6 and neuropathic mechanical allodynia after SNI. Our findings point to an important role of peripheral Sig-1R in sensory neuron-macrophage/monocyte communication in the DRG after peripheral nerve injury; thus, these receptors may contribute to the neuropathic pain phenotype 2021-03-11T08:12:48Z 2021-03-11T08:12:48Z 2020-04 journal article Bravo-Caparrós I, Ruiz-Cantero MC, Perazzoli G, Cronin SJF, Vela JM, Hamed MF, Penninger JM, Baeyens JM, Cobos EJ, Nieto FR. Sigma-1 receptors control neuropathic pain and macrophage infiltration into the dorsal root ganglion after peripheral nerve injury. FASEB J. 2020 Apr;34(4):5951-5966. http://hdl.handle.net/10481/67088 10.1096/fj.201901921R eng MINECO, grant SAF2016-80540-R http://creativecommons.org/licenses/by-nc-nd/3.0/es/ open access Atribución-NoComercial-SinDerivadas 3.0 España