mTOR-neuropeptide Y signaling sensitizes nociceptors to drive neuropathic pain

Abstract

Neuropathic pain is a refractory condition that involves de novo protein synthesis in the nociceptive pathway. The mechanistic target of rapamycin (mTOR) is a master regulator of protein translation; however, mechanisms underlying its role in neuropathic pain remain elusive. Using spared nerve injury-induced neuropathic pain model, we found that mTOR is preferentially activated in large-diameter dorsal root ganglion (DRG) neurons and spinal microglia. However, selective ablation of mTOR in DRG neurons, rather than microglia, alleviated neuropathic pain. We show that injury- induced mTOR activation promoted transcriptional induction of NPY likely via signal transducer and activator of transcription 3 (STAT3) phosphorylation. NPY further acted primarily on Y2 receptors (Y2R) to enhance nociceptor excitability. Peripheral replenishment of NPY reversed pain alleviation upon mTOR removal, whereas Y2R antagonists prevented pain restoration. Our findings reveal an unexpected link between mTOR and NPY in promoting nociceptor sensitization and neuropathic pain, through NPY/Y2R signaling-mediated intra-ganglionic transmission.

Avaliação da expressão gênica de marcadores inflamatórios em células mononucleares de pacientes com trombose venosa profunda

“…Microarray analysis have been performed to evaluate the gene expression disease-associated; pulmonary embolism patients had different gene expression of immune or inflammatory, metabolism and apoptosis from peripheral blood [4]; genes related with inflammation were upregulated in adipocytes of obese subject [5] and type 2 diabetes mellitus patients expressed differentially 1320 genes involved in several biological process in mononuclear cells [6].…”