Spinal Microglia Maintain Multiple Sclerosis-Associated Neuropathic Pain

The contribution of microglia to multiple sclerosis associated neuropathic pain (MSNP) is poorly understood. Adult male and female mice, some created with tamoxifen-inducible CX3CR1-CreER::hM4Di-DREADD transgenes, underwent experimental autoimmune encephalomyelitis with the subcutaneous injection of MOG33-55 and complete Freund ’s adjuvant in the absence of pertussis toxin (EAE-nPTX). EAE-nPTX mice rapidly developed plantar hypersensitivity to mechanical and cold stimuli, and then they and their controls (CFA without MOG35-55 and naïve groups without injections) received either: 1) Global CNS depletion of microglia with a colony-stimulating factor 1 receptor (CSFR1) inhibitor, PLX3397 (600ppm in chow); 2) Local microglial depletion at the spinal cord or brain with injection of liposome encapsulated clodronate (LEC) by the intrathecal (50µL/10µL, i.t.) or intracerebroventricular route (50µg/10µL); or 3) in tran sgenic mice, reversible inhibition of global CNS or spinal cord microglia with the injection of clozapine N-oxide (CNO) by the intraperitoneal (3mg/kg) or i.t.
Source: The Journal of Pain - Category: Materials Science Authors: Source Type: research