Mirogabalin Decreases Pain-like Behaviors by Inhibiting the Microglial/Macrophage Activation, p38MAPK Signaling, and Pronociceptive CCL2 and CCL5 Release in a Mouse Model of Neuropathic Pain

Neuropathic pain is a chronic condition that significantly reduces the quality of life many patients as result ineffective relief therapy. For reason, looking for new analgesics remains an important issue. Mirogabalin gabapentinoid specific ligand α2σ-1 and α2σ-2 subunits voltage-gated calcium channels. In present study, we compared analgesic effect pregabalin mirogabalin in neuropathic constriction injury (CCI) sciatic nerve mouse model. The main purpose our study was to determine effectiveness administered both once repeatedly explain how drug influences highly activated cells at spinal cord level neuropathy. We also sought understand whether modulates selected intracellular pathways (p38MAPK, ERK, JNK) chemokines (CCL2, CCL5) nociceptive transmission, which crucial information from clinical perspective. First, provides evidence single administration diminishes tactile hypersensitivity more effectively than pregabalin. Second, research shows several indirect mechanisms may be responsible beneficial mirogabalin. This reports repeated intraperitoneally (i.p.) strongly prevents microglia/macrophage activation evoked by injury, slightly suppresses astroglia neutrophil infiltration, p38MAPK levels associated with pain, measured on Day 7. Moreover, diminished pronociceptive CCL2 CCL5. Our results indicate represent strategy effective pharmacotherapy pain.