Evidence map›Paper›PMID 40968661›Full record

ArticleMolecular pain

Inhibition of mTOR/S6K1/Gli1 signaling alleviates morphine-induced thermal hyperalgesia and tolerance.

Xing-He Wang, Long Wang, Long Yang, Yang Bai, Ling-Fei Xu, Miao-Miao Li, Yu-Cheng Liu, Jia Sun, Su Liu

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Article in Molecular pain. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Not yet cited in PubMed.

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1 · What the graph read from it

What it found

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The abstract states no effect estimate the extractor could read, or names no intervention and outcome on the map, so this paper lights no cell and moves no belief. It is still indexed, cited and linked below.

2 · The registry

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3 · Its place in the literature

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4 · The record

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5 · Who and what money

Authors and funding

9 authors.

Xing-He WangJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China.
Long WangDepartment of Anesthesiology, Xuzhou Central Hospital, Xuzhou, China.
Long YangDepartment of Anesthesiology, Xuzhou New Health Hospital, Xuzhou, China.
Yang BaiJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China.
Ling-Fei XuJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China.
Miao-Miao LiJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China.
Yu-Cheng LiuJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China.
Jia SunDepartment of Anesthesiology, Xuzhou Central Hospital, Xuzhou, China.ORCID 0000-0003-3595-8932
Su LiuJiangsu Province Key Laboratory of Anesthesiology, Jiangsu Province Key Laboratory of Anesthesia and Analgesia Application Technology, NMPA Key Laboratory for Research and Evaluation of Narcotic and Psychotropic Drugs, Xuzhou Medical University, Jiangsu, China.ORCID 0009-0008-0645-3496

Funding

No grant is acknowledged in the PubMed record.

6 · The paper itself

Abstract

aimsThe precise mechanisms underlying the pathogenesis of opioid-induced thermal hyperalgesia and tolerance are not yet fully understood.

methodsIn adult CD-1 mice, repeated morphine treatment was used to examine the expression of the non-canonical pathway of sonic hedgehog signaling, behavioral changes, and neurochemical alterations induced by morphine in the spinal cord and DRG. Additionally, to delve into the underlying mechanisms of the non-canonical pathway of Shh signaling in morphine-induced thermal hyperalgesia (MITH) and tolerance, we utilize the brain-derived neurotrophic factor (BDNF) inhibitor.

resultsMorphine administration repeatedly resulted in apparent thermal hyperalgesia and tolerance. The initiation and maintenance of MITH and tolerance, as well as related neurochemical alterations, were greatly inhibited by pharmacological and genetic suppression of the mTOR. By blocking the mTOR/p70 ribosomal S6 protein kinase 1 (S6K1)/Gli1 signaling, the morphine-induced increase in BDNF was considerably inhibited. Moreover, mTOR activator injection in naive mice resulted in significant heat hyperalgesia and BDNF upregulation. Suppression of BDNF effectively mitigated the development of thermal hyperalgesia induced by the mTOR activator.

conclusionThese findings indicate that the non-canonical pathway of Shh signaling might serve as a crucial mediator in the development of MITH and tolerance through the regulation of BDNF expression.

Indexed as

Drug ToleranceHyperalgesiaMorphineRibosomal Protein S6 Kinases, 90-kDaSignal TransductionTOR Serine-Threonine KinasesZinc Finger Protein GLI1AnimalsBrain-Derived Neurotrophic FactorGanglia, SpinalHedgehog ProteinsMaleMiceSpinal CordBrain-Derived Neurotrophic FactorGli1 protein, mouseHedgehog ProteinsMorphinemTOR protein, mouseRibosomal Protein S6 Kinases, 90-kDaTOR Serine-Threonine KinasesZinc Finger Protein GLI1Hedgehoghyperalgesiamammalian target of rapamycinmorphine

Identifiers

PMID40968661
PMCPMC12446821

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Read under generation 80e0d062 · epoch 390. Bibliography from PubMed, PubMed Central and OpenAlex; grants from NIH RePORTER; trial links from ClinicalTrials.gov; estimates, votes and beliefs from the Socratic graph.