title: Minocycline injection in the ventral posterolateral thalamus reverses microglial reactivity and thermal hyperalgesia secondary to sciatic neuropathy.
abstract: We hypothesized that microglia in the ventral posterolateral (VPL) nucleus of the thalamus are reactive following peripheral nerve injury, and that inhibition of microglia by minocycline injection in the VPL attenuates thermal hyperalgesia. Our results show increased expression of OX-42 co-localized with phosphorylated p38MAPK (P-p38) in the VPL seven days after chronic constriction injury (CCI) of the sciatic nerve. However, astrocytic GFAP expression in the VPL is unchanged 7 and 14 days after CCI. Microinjection of minocycline into the VPL contralateral to CCI reverses thermal hyperalgesia, whereas vehicle injection has no effect on paw withdrawal latency. Minocycline abrogates the increased expression of OX-42 in the VPL after CCI. Therefore, peripheral nerve injury favors a hyperactive microglial phenotype in the VPL, suggesting remote neuroimmune signaling from the damaged nerve to the brain, concomitant with neuropathic behavior that is reversed by local intervention in the VPL to inhibit microglia.
authors.affiliation: Department of Neurosurgery, Rhode Island Hospital and Brown Alpert Medical School, RI 02903, USA.
authors.forename: Brian W
authors.initials: BW
authors.lastname: LeBlanc
authors.forename: Michele L
authors.initials: ML
authors.lastname: Zerah
authors.forename: Laith M
authors.initials: LM
authors.lastname: Kadasi
authors.forename: Noori
authors.initials: N
authors.lastname: Chai
authors.forename: Carl Y
authors.initials: CY
authors.lastname: Saab
mesh_terms: D000818:Animals; D000911:Antibodies, Monoclonal / Q000096:biosynthesis / Q000235:genetics; D005786:Gene Expression Regulation; D005904:Glial Fibrillary Acidic Protein / Q000096:biosynthesis / Q000235:genetics; D006358:Hot Temperature / Q000009:adverse effects; D006930:Hyperalgesia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D008297:Male; D017628:Microglia / Q000187:drug effects* / Q000473:pathology; D008911:Minocycline / Q000008:administration & dosage / Q000494:pharmacology* / Q000627:therapeutic use; D009419:Nerve Tissue Proteins / Q000096:biosynthesis / Q000235:genetics; D009437:Neuralgia / Q000188:drug therapy / Q000209:etiology / Q000503:physiopathology*; D009473:Neuronal Plasticity / Q000187:drug effects* / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012584:Sciatic Nerve / Q000293:injuries*; D020651:Ventral Thalamic Nuclei / Q000187:drug effects* / Q000503:physiopathology; D048051:p38 Mitogen-Activated Protein Kinases / Q000378:metabolism
chemical_list: D000911:Antibodies, Monoclonal; D005904:Glial Fibrillary Acidic Protein; D009419:Nerve Tissue Proteins; D048051:p38 Mitogen-Activated Protein Kinases; D008911:Minocycline