Sigma-1 receptors control neuropathic pain and macrophage infiltration into the dorsal root ganglion after peripheral nerve injury.

FASEB Journal : Official Publication of the Federation of American Societies for Experimental Biology
Inmaculada Bravo-CaparrósFrancisco R Nieto

Abstract

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 comm...Continue Reading

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Citations

Jun 17, 2020·Pharmaceutical Patent Analyst·Pasquale LincianoSimona Collina
Oct 24, 2020·Cellular and Molecular Neurobiology·Simon CoulyTsung-Ping Su
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Oct 12, 2021·Experimental and Therapeutic Medicine·Sai-Sai HuangShi-Ren Shen

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