title: mTOR and Erk1/2 Signaling in the Cerebrospinal Fluid-Contacting Nucleus is Involved in Neuropathic Pain.
abstract: The cerebrospinal fluid-contacting nucleus (CSF-CN) has been demonstrated to be involved in neuropathic pain, but the underlying molecular mechanisms remain unclear. Previous work has shown that mTOR and ERK1/2 are important signaling pathways regulating neuropathic pain. However, studies on the interactions between these major pathways in neuropathic pain are very rare. Therefore, the purpose of this study is to determine whether mTOR and ERK1/2 exist in the CSF-CN and elucidate their alterations in neuropathic pain, especially, the crosstalk between them. Our results showed that mTOR and ERK1/2 were distributed in the CSF-CN, and their expression levels were increased in chronic constriction injury (CCI)-induced neuropathic pain. Furthermore, the injection of both the mTOR antagonist rapamycin and the ERK1/2 antagonist U0126 into the lateral ventricle of the brain attenuated CCI-induced neuropathic pain. Inhibition of the ERK1/2 pathway had little impact on mTOR signaling, but inhibition of the mTOR pathway significantly increased ERK/2 signaling. The coadministration of rapamycin and U0126 inhibited the rapamycin-induced upregulation of ERK, and had a greater effect on pain behaviors than did the single-drug administrations. These data extend our understanding of the relationship between mTOR and ERK in the supraspinal site and demonstrate that the CSF-CN participates in neuropathic pain via the regulation of mTOR and ERK1/2.
authors.affiliation: Jiangsu Province Key Laboratory of Anesthesiology, Xuzhou Medical College, Xuzhou, Jiangsu Province, China.
authors.forename: Guangling
authors.initials: G
authors.lastname: Li
authors.forename: Xianfu
authors.initials: X
authors.lastname: Lu
authors.forename: Suming
authors.initials: S
authors.lastname: Zhang
authors.forename: Qiangqiang
authors.initials: Q
authors.lastname: Zhou
authors.forename: Licai
authors.initials: L
authors.lastname: Zhang
mesh_terms: D000818:Animals; D002467:Cell Nucleus / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D002555:Cerebrospinal Fluid / Q000737:chemistry / Q000187:drug effects / Q000378:metabolism*; D020935:MAP Kinase Signaling System / Q000187:drug effects / Q000502:physiology*; D008297:Male; D009437:Neuralgia / Q000378:metabolism*; D010147:Pain Measurement / Q000379:methods; D051381:Rats; D017207:Rats, Sprague-Dawley; D020123:Sirolimus / Q000494:pharmacology; D058570:TOR Serine-Threonine Kinases / Q000032:analysis / Q000037:antagonists & inhibitors / Q000378:metabolism*
chemical_list: C546845:mTOR protein, rat; D058570:TOR Serine-Threonine Kinases; D020123:Sirolimus
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