title: mTOR kinase: a possible pharmacological target in the management of chronic pain.
abstract: Chronic pain represents a major public health problem worldwide. Current pharmacological treatments for chronic pain syndromes, including neuropathic pain, are only partially effective, with significant pain relief achieved in 40-60% of patients. Recent studies suggest that the mammalian target of rapamycin (mTOR) kinase and downstream effectors may be implicated in the development of chronic inflammatory, neuropathic, and cancer pain. The expression and activity of mTOR have been detected in peripheral and central regions involved in pain transmission. mTOR immunoreactivity was found in primary sensory axons, in dorsal root ganglia (DRG), and in dorsal horn neurons. This kinase is a master regulator of protein synthesis, and it is critically involved in the regulation of several neuronal functions, including the synaptic plasticity that is a major mechanism leading to the development of chronic pain. Enhanced activation of this pathway is present in different experimental models of chronic pain. Consistently, pharmacological inhibition of the kinase activity turned out to have significant antinociceptive effects in several experimental models of inflammatory and neuropathic pain. We will review the main evidence from animal and human studies supporting the hypothesis that mTOR may be a novel pharmacological target for the management of chronic pain.
authors: Institute of Pharmacology, Catholic University Medical School, Largo F. Vito 1, 00168 Rome, Italy.
authors: Lucia
authors: 0000-0003-1397-2426
authors: L
authors: Lisi
authors: Department of Anesthesiology and Intensive Care, A. Gemelli Hospital, Catholic University Medical School, 00168 Rome, Italy.
authors: Paola
authors: P
authors: Aceto
authors: Institute of Pharmacology, Catholic University Medical School, Largo F. Vito 1, 00168 Rome, Italy.
authors: Pierluigi
authors: P
authors: Navarra
authors: Institute of Pharmacology, Catholic University Medical School, Largo F. Vito 1, 00168 Rome, Italy.
authors: Cinzia
authors: 0000-0002-2538-3832
authors: C
authors: Dello Russo
mesh_terms: D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy / Q000201:enzymology; D005727:Ganglia, Spinal / Q000201:enzymology*; D006801:Humans; D009437:Neuralgia / Q000188:drug therapy / Q000201:enzymology; D059408:Pain Management; D011984:Sensory Receptor Cells / Q000201:enzymology*; D058570:TOR Serine-Threonine Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C546842:MTOR protein, human; D058570:TOR Serine-Threonine Kinases