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Sigma‐1 receptors control neuropathic pain and macrophage infiltration into the dorsal root ganglion after peripheral nerve injury
Author(s) -
BravoCaparrós Inmaculada,
RuizCantero M. Carmen,
Perazzoli Gloria,
Cronin Shane J. F.,
Vela José M.,
Hamed Mohamed F.,
Penninger Josef M.,
Baeyens José M.,
Cobos Enrique J.,
Nieto Francisco R.
Publication year - 2020
Publication title -
the faseb journal
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.709
H-Index - 277
eISSN - 1530-6860
pISSN - 0892-6638
DOI - 10.1096/fj.201901921r
Subject(s) - sni , neuropathic pain , nerve injury , dorsal root ganglion , peripheral nerve injury , medicine , atf3 , sciatic nerve , neuroinflammation , neuroscience , anesthesia , anatomy , inflammation , chemistry , biology , dorsum , gene expression , biochemistry , promoter , gene , hydrolysis , acid hydrolysis
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.