nsc-74859 and Pain

Painful neuropathy, as a severe side effect of chemotherapeutic bortezomib, is the most common reason for treatment discontinuation. However, the mechanism by which administration of bortezomib leads to painful neuropathy remains unclear. In the present study, we found that application of bortezomib significantly increased the expression of NOD-like receptor family pyrin domain containing 3 (NLRP3) and phosphorylated signal transducer and activator of transcription-3 (STAT3) in dorsal root ganglion (DRG). Intrathecal injection of NLRP3 siRNA significantly prevented the mechanical allodynia induced by bortezomib treatment, and intrathecal injection of recombinant adeno-associated virus vector encoding NLRP3 markedly decreased paw withdrawal threshold of naive rats. Furthermore, the expressions of p-STAT3 were colocalized with NLRP3-positive cells in DRG neurons, and inhibition of STAT3 by intrathecal injection of AAV-Cre-GFP into STAT3

Topics: Acetylation; Aminosalicylic Acids; Animals; Antineoplastic Agents; Benzenesulfonates; Bortezomib; Disease Models, Animal; Ganglia, Spinal; Green Fluorescent Proteins; Histones; Hyperalgesia; Male; Nerve Tissue Proteins; NLR Family, Pyrin Domain-Containing 3 Protein; Pain; Peripheral Nervous System Diseases; Rats; Rats, Sprague-Dawley; RNA, Messenger; RNA, Small Interfering; STAT3 Transcription Factor; Transfection; Up-Regulation