256
Views
0
CrossRef citations to date
0
Altmetric
Review Articles

Research progress of p38 as a new therapeutic target against morphine tolerance and the current status of therapy of morphine tolerance

ORCID Icon &
Pages 152-165 | Received 22 Jul 2022, Accepted 11 Oct 2022, Published online: 02 Nov 2022

References

  • Jagjit P. Report of the international narcotics control board 2021.Vienna: United Nations International Narcotics Control Programme. 2022. 2.
  • Azzam AAH, McDonald J, Lambert DG. Hot topics in opioid pharmacology: mixed and biased opioids. Br J Anaesth. 2019;122(6):e136–e145.
  • Boorman DC, Keay KA. Escalating morphine dosage fails to elicit conditioned analgesia in a preclinical chronic neuropathic pain model. Behav Pharmacol. 2021;32(6):479–486.
  • Agnoli A, Xing G, Tancredi DJ, et al. Association of dose tapering with overdose or mental health crisis among patients prescribed long-term opioids. JAMA. 2021;326(5):411–419.
  • Walsh TD. Oral morphine in chronic cancer pain. Pain. 1984;18(1):1–11.
  • Ferguson RK, Mitchell CL. Pain as a factor in the development of tolerance to morphine analgesia in man. Clin Pharmacol Ther. 1969;10(3):372–382.
  • Caspi O, Naami R, Halfin E, et al. Adverse dose-dependent effects of morphine therapy in acute heart failure. Int J Cardiol. 2019;293:131–136.
  • Tas B, Jolley CJ, Kalk NJ, et al. Heroin-induced respiratory depression and the influence of dose variation: within-subject between-session changes following dose reduction. Addiction. 2020;115(10):1954–1959.
  • Jipa M, Isac S, Klimko A, et al. Opioid-Sparing analgesia impacts the perioperative anesthetic management in major abdominal surgery. Medicina (Kaunas). 2022;58(4):487.
  • Chen Y, Sommer C. The role of mitogen-activated protein kinase (MAPK) in morphine tolerance and dependence. Mol Neurobiol. 2009;40(2):101–107.
  • Ronkina N, Gaestel M. MAPK-Activated protein kinases: servant or partner? Annu Rev Biochem. 2022;91:505–540.
  • Lee S, Rauch J, Kolch W. Targeting MAPK signaling in cancer: mechanisms of drug resistance and sensitivity. IJMS. 2020;21(3):1102.
  • De Freitas BG, Pereira LM, Santa-Cecília FV, et al. Mitogen-Activated protein kinase signaling mediates morphine Induced-Delayed hyperalgesia. Front Neurosci. 2019;13:1018.
  • Cui Y, Chen Y, Zhi JL, et al. Activation of p38 mitogen-activated protein kinase in spinal microglia mediates morphine antinociceptive tolerance. Brain Res. 2006;1069(1):235–243.
  • Sertürner FW. Darstellung der reinen mohnsäure (opiumsäure) nebst einer chemischen untersuchung des opiums mit vorzüglicher hinsicht auf einen darin neuen stoff und die dahin gehöringen bemerkungen Trommdorfs J Pharm. 1806;14(1):47–93.
  • Hamamoto-Hardman BD, Baden RW, McKemie DS, et al. Equine uridine diphospho-glucuronosyltransferase 1A1, 2A1, 2B4, 2B31: cDNA cloning, expression and initial characterization of morphine metabolism. Vet Anaesth Analg. 2020;47(6):763–772.
  • Hahn D, Emoto C, Euteneuer JC, et al. Influence of OCT1 ontogeny and genetic variation on morphine disposition in critically ill neonates: lessons from PBPK modeling and clinical study. Clin Pharmacol Ther. 2019;105(3):761–768.
  • Verscheijden LFM, Litjens CHC, Koenderink JB, et al. Physiologically based pharmacokinetic/pharmacodynamic model for the prediction of morphine brain disposition and analgesia in adults and children. PLoS Comput Biol. 2021;17(3):e1008786.
  • Liu P, Chu Z, Lei G, et al. The role of HINT1 protein in morphine addiction: an animal model-based study. Addict Biol. 2021;26(2):e12897.
  • Christrup LL. Morphine metabolites[J]. Acta Anaesthesiol Scand. 1997;41(1 Pt 2):116–122.
  • Smith GD, Smith MT. Morphine-3-glucuronide: evidence to support its putative role in the development of tolerance to the antinociceptive effects of morphine in the rat. Pain. 1995;62(1):51–60.
  • Ochiai W, Kaneta M, Nagae M, et al. Mice with neuropathic pain exhibit morphine tolerance due to a decrease in the morphine concentration in the brain. Eur J Pharm Sci. 2016;92:298–304.
  • Weinsanto I, Laux-Biehlmann A, Mouheiche J, et al. Stable isotope-labelled morphine to study in vivo Central and peripheral morphine glucuronidation and brain transport in tolerant mice. Br J Pharmacol. 2018;175(19):3844–3856.
  • Hamamoto-Hardman BD, Steffey EP, Weiner D, et al. Pharmacokinetics and selected pharmacodynamics of morphine and its active metabolites in horses after intravenous administration of four doses. J Vet Pharmacol Ther. 2019;42(4):401–410.
  • Blomqvist KJ, Viisanen H, Ahlström FHG, et al. Morphine-3-glucuronide causes antinociceptive cross-tolerance to morphine and increases spinal substance P expression. Eur J Pharmacol. 2020;875:173021.
  • Wang K, Wang J, Liu T, et al. Morphine-3-glucuronide upregulates PD-L1 expression via TLR4 and promotes the immune escape of non-small cell lung cancer. Cancer Biol Med. 2021;18(1):155–171.
  • Iqbal S, Parker LM, Everest-Dass AV, et al. Lipopolysaccharide and morphine-3-Glucuronide-Induced immune signalling increases the expression of polysialic acid in PC12 cells. Mol Neurobiol. 2020;57(2):964–975.
  • Wang L, Ni C, Shen H, et al. Comparison of the detection windows of heroin metabolites in human urine using online SPE and LC-MS/MS: importance of morphine-3-Glucuronide. J Anal Toxicol. 2020;44(1):22–28.
  • Dozio V, Daali Y, Desmeules J, et al. Deep proteomics and phosphoproteomics reveal novel biological pathways perturbed by morphine, morphine-3-glucuronide and morphine-6-glucuronide in human astrocytes. J Neurosci Res. 2022;100(1):220–236.
  • Ihmsen H, Schüttler J, Jeleazcov C. Pharmacokinetics of morphine and morphine-6-Glucuronide during postoperative pain therapy in cardiac surgery patients. Eur J Drug Metab Pharmacokinet. 2021;46(2):249–263.
  • Imaoka T, Huang W, Shum S, et al. Bridging the gap between in silico and in vivo by modeling opioid disposition in a kidney proximal tubule microphysiological system. Sci Rep. 2021;11(1):21356.
  • Gabel F, Hovhannisyan V, Andry V, et al. Central metabolism as a potential origin of sex differences in morphine antinociception but not induction of antinociceptive tolerance in mice. Br J Pharmacol. 2022;
  • Ferrini F, Trang T, Mattioli TA, et al. Morphine hyperalgesia gated through microglia-mediated disruption of neuronal Cl- homeostasis. Nat Neurosci. 2013;16(2):183–192.
  • Hu XM, Yang W, Zhang MT, et al. Glial IL-33 signaling through an ST2-to-CXCL12 pathway in the spinal cord contributes to morphine-induced hyperalgesia and tolerance. Sci Signal. 2021;14(699):eabe3773.
  • Roeckel LA, Utard V, Reiss D, et al. Morphine-induced hyperalgesia involves mu opioid receptors and the metabolite morphine-3-glucuronide. Sci Rep. 2017;7(1):10406.
  • Chao PK, Chang HF, Ou LC, et al. Convallatoxin enhance the ligand-induced mu-opioid receptor endocytosis and attenuate morphine antinociceptive tolerance in mice. Sci Rep. 2019;9(1):2405.
  • Pantouli F, Grim TW, Schmid CL, et al. Comparison of morphine, oxycodone and the biased MOR agonist SR-17018 for tolerance and efficacy in mouse models of pain. Neuropharmacology. 2021;185:108439.
  • Wang W, Ma X, Luo L, et al. Exchange factor directly activated by cAMP-PKCε signalling mediates chronic morphine-induced expression of purine P2X3 receptor in rat dorsal root ganglia. Br J Pharmacol. 2018;175(10):1760–1769.
  • Wang J, Xu W, Shao J, et al. miR-219-5p targets CaMKIIγ to attenuate morphine tolerance in rats. Oncotarget. 2017;8(17):28203–28214.
  • Ozcan S, Bulmus O, Ulker N, et al. Agomelatine potentiates anti-nociceptive effects of morphine in a mice model for diabetic neuropathy: involvement of NMDA receptor subtype NR1 within the raphe nucleus and periaqueductal grey. Neurol Res. 2020;42(7):554–563.
  • Neyama H, Dozono N, Ueda H. NR2A-NMDA receptor blockade reverses the lack of morphine analgesia without affecting chronic pain status in a Fibromyalgia-Like mouse model. J Pharmacol Exp Ther. 2020;373(1):103–112.
  • Deng M, Chen SR, Chen H, et al. Mitogen-activated protein kinase signaling mediates opioid-induced presynaptic NMDA receptor activation and analgesic tolerance. J Neurochem. 2019;148(2):275–290.
  • Lim G, Wang S, Zeng Q, et al. Evidence for a long-term influence on morphine tolerance after previous morphine exposure: role of neuronal glucocorticoid receptors. Pain. 2005;114(1-2):81–92.
  • Tertil M, Skupio U, Kudla L, et al. Astroglial knockout of glucocorticoid receptor attenuates morphine withdrawal symptoms, but not antinociception and tolerance in mice. Cell Mol Neurobiol. 2022;42(7):2423–2426.
  • Wu Q, Zhang L, Law PY, et al. Long-term morphine treatment decreases the association of mu-opioid receptor (MOR1) mRNA with polysomes through miRNA23b. Mol Pharmacol. 2009;75(4):744–750.
  • Wu Q, Hwang CK, Zheng H, et al. MicroRNA 339 down-regulates μ-opioid receptor at the post-transcriptional level in response to opioid treatment. Faseb J. 2013;27(2):522–535.
  • Garcia-Concejo A, Jimenez-Gonzalez A, Rodríguez RE. μ Opioid receptor expression after morphine administration is regulated by miR-212/132 cluster. PLoS One. 2016;11(7):e0157806.
  • Lu Z, Xu J, Xu M, et al. Morphine regulates expression of μ-opioid receptor MOR-1A, an intron-retention carboxyl terminal splice variant of the μ-opioid receptor (OPRM1) gene via miR-103/miR-107. Mol Pharmacol. 2014;85(2):368–380.
  • He Y, Yang C, Kirkmire CM, et al. Regulation of opioid tolerance by let-7 family microRNA targeting the mu opioid receptor. J Neurosci. 2010;30(30):10251–10258.
  • Xie XJ, Ma LG, Xi K, et al. Effects of microRNA-223 on morphine analgesic tolerance by targeting NLRP3 in a rat model of neuropathic pain. Mol Pain. 2017;13:1744806917706582.
  • Wu XP, She RX, Yang YP, et al. MicroRNA-365 alleviates morphine analgesic tolerance via the inactivation of the ERK/CREB signaling pathway by negatively targeting β-arrestin2. J Biomed Sci. 2018;25(1):10.
  • Hu XM, Cao SB, Zhang HL, et al. Downregulation of miR-219 enhances brain-derived neurotrophic factor production in mouse dorsal root ganglia to mediate morphine analgesic tolerance by upregulating CaMKIIγ. Mol Pain. 2016;12:174480691666628.
  • Li H, Tao R, Wang J, et al. Upregulation of miR-375 level ameliorates morphine analgesic tolerance in mouse dorsal root ganglia by inhibiting the JAK2/STAT3 pathway. J Pain Res. 2017;10:1279–1287.
  • Neumann E, Hermanns H, Barthel F, et al. Expression changes of microRNA-1 and its targets connexin 43 and brain-derived neurotrophic factor in the peripheral nervous system of chronic neuropathic rats. Mol Pain. 2015;11:39.
  • Sanchez-Simon FM, Zhang XX, Loh HH, et al. Morphine regulates dopaminergic neuron differentiation via miR-133b. Mol Pharmacol. 2010;78(5):935–942.
  • Lu Y, Cao DL, Jiang BC, et al. MicroRNA-146a-5p attenuates neuropathic pain via suppressing TRAF6 signaling in the spinal cord. Brain Behav Immun. 2015;49:119–129.
  • Tapocik JD, Ceniccola K, Mayo CL, et al. MicroRNAs are involved in the development of Morphine-Induced analgesic tolerance and regulate functionally relevant changes in Serpini1. Front Mol Neurosci. 2016;9:20.
  • Li W, He S, Zhou Y, et al. Neurod1 modulates opioid antinociceptive tolerance via two distinct mechanisms. Biol Psychiatry. 2014;76(10):775–784.
  • Yuan L, Luo L, Ma X, et al. Chronic morphine induces cyclic adenosine monophosphate formation and hyperpolarization-activated cyclic nucleotide-gated channel expression in the spinal cord of mice. Neuropharmacology. 2020;176:108222.
  • Grim TW, Schmid CL, Stahl EL, et al. A G protein signaling-biased agonist at the μ-opioid receptor reverses morphine tolerance while preventing morphine withdrawal. Neuropsychopharmacology. 2020;45(2):416–425.
  • Muchhala KH, Jacob JC, Dewey WL, et al. Role of β-arrestin-2 in short- and long-term opioid tolerance in the dorsal root ganglia. Eur J Pharmacol. 2021;899:174007.
  • Quanhong Z, Ying X, Moxi C, et al. Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance. Brain Res. 2012;1472:38–44.
  • Zhang L, Meng J, Ban Y, et al. Morphine tolerance is attenuated in germfree mice and reversed by probiotics, implicating the role of gut microbiome. Proc Natl Acad Sci U S A. 2019;116(27):13523–13532.
  • Du ER, Fan RP, Rong LL, et al. Regulatory mechanisms and therapeutic potential of microglial inhibitors in neuropathic pain and morphine tolerance. J Zhejiang Univ Sci B. 2020;21(3):204–217.
  • Ruhela D, Bhopale VM, Yang M, et al. Blood-borne and brain-derived microparticles in morphine-induced anti-nociceptive tolerance. Brain Behav Immun. 2020;87:465–472.
  • Sanna MD, Borgonetti V, Galeotti N. μ Opioid Receptor-Triggered notch-1 activation contributes to morphine tolerance: role of neuron-glia communication. Mol Neurobiol. 2020;57(1):331–345.
  • Ma R, Kutchy NA, Hu G. Astrocyte-Derived extracellular Vesicle-Mediated activation of primary ciliary signaling contributes to the development of morphine tolerance. Biol Psychiatry. 2021;90(8):575–585.
  • Wang L, Yin C, Xu X, et al. Pellino1 contributes to morphine tolerance by microglia activation via MAPK signaling in the spinal cord of mice. Cell Mol Neurobiol. 2020;40(7):1117–1131.
  • Li Z, Peng X, Jia X, et al. Spinal heat shock protein 27 participates in PDGFRβ-mediated morphine tolerance through PI3K/akt and p38 MAPK signalling pathways. Br J Pharmacol. 2020;177(22):5046–5062.
  • Urjanski AG, Vaqué JP, Gutkind JS. MAP kinases and the control of nuclear events. Oncogene. 2007;26(22):3240–3253.
  • Stein B, Yang MX, Young DB, et al. p38-2, a novel mitogen-activated protein kinase with distinct properties. J Biol Chem. 1997;272(31):19509–19517.
  • Umasuthan N, Bathige SD, Noh JK, et al. Gene structure, molecular characterization and transcriptional expression of two p38 isoforms (MAPK11 and MAPK14) from rock bream (oplegnathus fasciatus). Fish Shellfish Immunol. 2015;47(1):331–343.
  • Li Z, Jiang Y, Ulevitch RJ, et al. The primary structure of p38 gamma: a new member of p38 group of MAP kinases. Biochem Biophys Res Commun. 1996;228(2):334–340.
  • White A, Pargellis CA, Studts JM, et al. Molecular basis of MAPK-activated protein kinase 2:p38 assembly. Proc Natl Acad Sci U S A. 2007;104(15):6353–6358.
  • Kumar GS, Clarkson MW, Kunze MBA, et al. Dynamic activation and regulation of the mitogen-activated protein kinase p38. Proc Natl Acad Sci U S A. 2018;115(18):4655–4660.
  • Beenstock J, Melamed D, Mooshayef N, et al. p38β Mitogen-Activated protein kinase modulates its own basal activity by autophosphorylation of the activating residue Thr180 and the inhibitory residues Thr241 and Ser261. Mol Cell Biol. 2016;36(10):1540–1554.
  • Cuenda A, Rousseau S. p38 MAP-kinases pathway regulation, function and role in human diseases. Biochim Biophys Acta. 2007;1773(8):1358–1375.
  • Li Z, Dai A, Yang M, et al. p38MAPK signaling pathway in osteoarthritis: pathological and therapeutic aspects. J Inflamm Res. 2022;15:723–734.
  • Revuelta M, Elicegui A, Scheuer T, et al. In vitro P38MAPK inhibition in aged astrocytes decreases reactive astrocytes, inflammation and increases nutritive capacity after oxygen-glucose deprivation. Aging (Albany NY). 2021;13(5):6346–6358.
  • Xu C-J, Li M-Q, Chen W-G, et al. Short-term high-fat diet favors the appearances of apoptosis and gliosis by activation of ERK1/2/p38MAPK pathways in brain. Aging (Albany NY). 2021;13(19):23133–23148.
  • Liu J, Shao T, Zhang J, et al. Gamma synuclein promotes cancer metastasis through the MKK3/6-p38MAPK Cascade. Int J Biol Sci. 2022;18(8):3167–3177.
  • Liao CR, Wang SN, Zhu SY, et al. Advanced oxidation protein products increase TNF-α and IL-1β expression in chondrocytes via NADPH oxidase 4 and accelerate cartilage degeneration in osteoarthritis progression. Redox Biol. 2020;28:101306.
  • Ji RR, Suter MR. p38 MAPK, microglial signaling, and neuropathic pain. Mol Pain. 2007;3:33.
  • Qian Z, Chang J, Jiang F, et al. Excess administration of miR-340-5p ameliorates spinal cord injury-induced neuroinflammation and apoptosis by modulating the P38-MAPK signaling pathway. Brain Behav Immun. 2020;87:531–542.
  • Dou B, Li Y, Ma J, et al. Role of neuroimmune crosstalk in mediating the anti-inflammatory and analgesic effects of acupuncture on inflammatory pain. Front Neurosci. 2021;15:695670.
  • Almela P, García-Nogales P, Romero A, et al. Effects of chronic inflammation and morphine tolerance on the expression of phospho-ERK 1/2 and phospho-P38 in the injured tissue. Naunyn Schmiedebergs Arch Pharmacol. 2009;379(3):315–323.
  • Clark AK, Yip PK, Grist J, et al. Inhibition of spinal microglial cathepsin S for the reversal of neuropathic pain. Proc Natl Acad Sci U S A. 2007;104(25):10655–10660.
  • Li X, Cheng XW, Hu L, et al. Cathepsin S activity controls ischemia-induced neovascularization in mice. Int J Cardiol. 2015;183:198–208.
  • Clark AK, Wodarski R, Guida F, et al. Cathepsin S release from primary cultured microglia is regulated by the P2X7 receptor. Glia. 2010;58(14):1710–1726.
  • Hsieh MJ, Lin CW, Chen MK, et al. Inhibition of cathepsin S confers sensitivity to methyl protodioscin in oral cancer cells via activation of p38 MAPK/JNK signaling pathways. Sci Rep. 2017;7:45039.
  • Wu H, Cheng XW, Hu L, et al. Cathepsin S activity controls Injury-Related vascular repair in mice via the TLR2-Mediated p38MAPK and PI3K-Akt/p-HDAC6 signaling pathway. Arterioscler Thromb Vasc Biol. 2016;36(8):1549–1557.
  • Xiao L, Han X, Wang XE, et al. Cathepsin S in the spinal microglia facilitates morphine-induced antinociceptive tolerance in rats. Neurosci Lett. 2019;690:225–231.
  • Zheng L, Ishii Y, Tokunaga A, et al. Neuroprotective effects of PDGF against oxidative stress and the signaling pathway involved. J Neurosci Res. 2010;88(6):1273–1284.
  • Yang P, Wu J, Miao L, et al. Platelet-Derived growth factor receptor-β regulates vascular smooth muscle cell phenotypic transformation and neuroinflammation after intracerebral hemorrhage in mice. Crit Care Med. 2016;44(6):e390–e402.
  • Puig S, Barker KE, Szott SR, et al. Spinal opioid tolerance depends upon Platelet-Derived growth factor receptor-β signaling, not μ-Opioid receptor internalization. Mol Pharmacol. 2020;98(4):487–496.
  • Jia X, Zhang A, Li Z, et al. Activation of spinal PDGFRβ in microglia promotes neuronal autophagy via p38 MAPK pathway in morphine-tolerant rats. J Neurochem. 2021;158(2):373–390.
  • Cheng Y, Sun F, Wang L, et al. Virus-induced p38 MAPK activation facilitates viral infection. Theranostics. 2020;10(26):12223–12240.
  • Zhang JK, Ding MJ, Liu H, et al. Regulator of G-protein signaling 14 protects the liver from ischemia-reperfusion injury by suppressing TGF-β-activated kinase 1 activation. Hepatology. 2022;75(2):338–352.
  • Wang H, Huang M, Wang W, et al. Microglial TLR4-induced TAK1 phosphorylation and NLRP3 activation mediates neuroinflammation and contributes to chronic morphine-induced antinociceptive tolerance. Pharmacol Res. 2021;165:105482.
  • Xu H, Xu T, Ma X, et al. Involvement of neuronal TGF-β activated kinase 1 in the development of tolerance to morphine-induced antinociception in rat spinal cord. Br J Pharmacol. 2015;172(11):2892–2904.
  • Khan A, Shal B, Khan AU, et al. Suppression of TRPV1/TRPM8/P2Y nociceptors by withametelin via downregulating MAPK signaling in mouse model of Vincristine-Induced neuropathic pain. IJMS. 2021;22(11):6084.
  • Xue C, Liu SX, Hu J, et al. Corydalis saxicola bunting total alkaloids attenuate paclitaxel-induced peripheral neuropathy through PKCε/p38 MAPK/TRPV1 signaling pathway. Chin Med. 2021;16(1):58.
  • Nguyen TL, Nam YS, Lee SY, et al. Repeated morphine administration increases TRPV1 mRNA expression and autoradiographic binding at supraspinal sites in the pain pathway. Biomol Ther (Seoul). 2022;30(4):328–333.
  • Bao Y, Gao Y, Yang L, et al. The mechanism of μ-opioid receptor (MOR)-TRPV1 crosstalk in TRPV1 activation involves morphine anti-nociception, tolerance and dependence. Channels (Austin). 2015;9(5):235–243.
  • Mazeto TK, Picada JN, Correa ÁP, et al. Antinociceptive and genotoxic assessments of the antagonist TRPV1 receptor SB-366791 on morphine-induced tolerance in mice. Naunyn Schmiedebergs Arch Pharmacol. 2020;393(3):481–490.
  • Chung AM. Calcitonin gene-related peptide (CGRP): role in peripheral nerve regeneration. Rev Neurosci. 2018;29(4):369–376.
  • Wu J, Liu S, Wang Z, et al. Calcitonin gene-related peptide promotes proliferation and inhibits apoptosis in endothelial progenitor cells via inhibiting MAPK signaling. Proteome Sci. 2018;16:18.
  • Hu SH, Guang Y, Wang WX. Protective effects of calcitonin Gene-Related Peptide-Mediated p38 Mitogen-Activated protein kinase pathway on severe acute pancreatitis in rats. Dig Dis Sci. 2019;64(2):447–455.
  • Wang Z, Ma W, Chabot JG, et al. Calcitonin gene-related peptide as a regulator of neuronal CaMKII-CREB, microglial p38-NFκB and astroglial ERK-Stat1/3 Cascades mediating the development of tolerance to morphine-induced analgesia. Pain. 2010;151(1):194–205.
  • Binshtok AM, Wang H, Zimmermann K, et al. Nociceptors are interleukin-1beta sensors. J Neurosci. 2008;28(52):14062–14073.
  • Liang Y, Chu H, Jiang Y, et al. Morphine enhances IL-1β release through toll-like receptor 4-mediated endocytic pathway in microglia. Purinergic Signal. 2016;12(4):637–645.
  • Hadschieff V, Drdla-Schutting R, Springer DN, et al. Fundamental sex differences in morphine withdrawal-induced neuronal plasticity. Pain. 2020;161(9):2022–2034.
  • Le MT, Mai TT, Huynh PNH, et al. Structure-based discovery of interleukin-33 inhibitors: a pharmacophore modelling, molecular docking, and molecular dynamics simulation approach. SAR QSAR Environ Res. 2020;31(12):883–904.
  • Tanaka T, Narazaki M, Kishimoto T. IL-6 in inflammation, immunity, and disease. Cold Spring Harb Perspect Biol. 2014;6(10):a016295.
  • Shankar-Hari M, Vale CL, WHO Rapid Evidence Appraisal for COVID-19 Therapies (REACT) Working Group, et al. Association between administration of IL-6 antagonists and mortality among patients hospitalized for COVID-19: a meta-analysis. JAMA. 2021;326(6):499–518.
  • Yu C, Li P, Wang YX, et al. Sanguinarine attenuates neuropathic pain by inhibiting P38 MAPK activated neuroinflammation in rat model. Drug Des Devel Ther. 2020;14:4725–4733.
  • Manjavachi MN, Motta EM, Marotta DM, et al. Mechanisms involved in IL-6-induced muscular mechanical hyperalgesia in mice. Pain. 2010;151(2):345–355.
  • Ridker PM, Devalaraja M, Baeres FMM, RESCUE Investigators, et al. IL-6 inhibition with ziltivekimab in patients at high atherosclerotic risk (RESCUE): a double-blind, randomised, placebo-controlled, phase 2 trial. Lancet. 2021;397(10289):2060–2069.
  • Ma M, Sun Q, Li X, et al. Blockade of IL-6/IL-6R signaling attenuates acute Antibody-Mediated rejection in a mouse cardiac transplantation model. Front Immunol. 2021;12:778359.
  • Lotan I, McGowan R, Levy M. Anti-IL-6 therapies for neuromyelitis optica spectrum disorders: a systematic review of safety and efficacy. Curr Neuropharmacol. 2021;19(2):220–232.
  • Houghtling RA, Bayer BM. Rapid elevation of plasma interleukin-6 by morphine is dependent on autonomic stimulation of adrenal gland. J Pharmacol Exp Ther. 2002;300(1):213–219.
  • Jindal S, Kumar N, Shah AA, et al. Histone deacetylase inhibitors prevented the development of morphine tolerance by decreasing IL6 production and upregulating μ-Opioid receptors. CNS Neurol Disord Drug Targets. 2021;20(2):190–198.
  • Ahmad KA, Shoaib RM, Ahsan MZ, et al. Microglial IL-10 and β-endorphin expression mediates gabapentinoids antineuropathic pain. Brain Behav Immun. 2021;95:344–361.
  • Stirm K, Leary P, Bertram K, et al. Tumor cell-derived IL-10 promotes cell-autonomous growth and immune escape in diffuse large B-cell lymphoma. Oncoimmunology. 2021;10(1):2003533.
  • Francisco S, Arranz A, Merino J, et al. Early p38 activation regulated by MKP-1 is determinant for high levels of IL-10 expression through TLR2 activation. Front Immunol. 2021;12:660065.
  • Tai YH, Tsai RY, Lin SL, et al. Amitriptyline suppresses neuroinflammation-dependent interleukin-10-p38 mitogen-activated protein kinase-heme oxygenase-1 signaling pathway in chronic morphine-infused rats. Anesthesiology. 2009;110(6):1379–1389.
  • Zaringhalam J, Hormozi A, Tekieh E, et al. Serum IL-10 involved in morphine tolerance development during adjuvant-induced arthritis. J Physiol Biochem. 2014;70(2):497–507.
  • Avcı O, Taşkıran AŞ. Anakinra, an interleukin-1 receptor antagonist, increases the morphine analgesic effect and decreases morphine tolerance development by modulating oxidative stress and endoplasmic reticulum stress in rats. Turk J Med Sci. 2020;50(8):2048–2058.
  • Shavit Y, Wolf G, Goshen I, et al. Interleukin-1 antagonizes morphine analgesia and underlies morphine tolerance. Pain. 2005;115(1-2):50–59.
  • Puig S, Donica CL, Gutstein HB. EGFR signaling causes morphine tolerance and mechanical sensitization in rats. eNeuro. 2020;7(2):ENEURO.0460-18.2020.
  • Zhang Y, Zhou P, Lu F, et al. A20-Binding inhibitor of nuclear factor-κB targets β-Arrestin2 to attenuate opioid tolerance. Mol Pharmacol. 2021;100(2):170–180.
  • Matalińska J, Lipiński PFJ, Kosson P, et al. In vivo, in vitro and in silico studies of the hybrid compound AA3266, an opioid agonist/NK1R antagonist with selective cytotoxicity. IJMS. 2020;21(20):7738.
  • Hall-Jackson CA, Goedert M, Hedge P, et al. Effect of SB 203580 on the activity of c-Raf in vitro and in vivo. Oncogene. 1999;18(12):2047–2054.
  • Paw M, Wnuk D, Nit K, et al. SB203580-A potent p38 MAPK inhibitor reduces the profibrotic bronchial fibroblasts transition associated with asthma. IJMS. 2021;22(23):12790.
  • Cheung S, Jain P, So J, et al. p38 MAPK inhibition mitigates Hypoxia-Induced AR signaling in Castration-Resistant prostate cancer. Cancers (Basel). 2021;13(4):831.
  • Zhao T, Kee HJ, Bai L, et al. Selective HDAC8 inhibition attenuates Isoproterenol-Induced cardiac hypertrophy and fibrosis via p38 MAPK pathway. Front Pharmacol. 2021;12:677757.
  • Gong X, Fan R, Zhu Q, et al. Exercise reduces Morphine-Induced hyperalgesia and antinociceptive tolerance. Biomed Res Int. 2021;2021:6667474.
  • Wang Z, Chabot JG, Quirion R. On the possible role of ERK, p38 and CaMKII in the regulation of CGRP expression in morphine-tolerant rats. Mol Pain. 2011;7:68.
  • Cui Y, Liao XX, Liu W, et al. A novel role of minocycline: attenuating morphine antinociceptive tolerance by inhibition of p38 MAPK in the activated spinal microglia. Brain Behav Immun. 2008;22(1):114–123.
  • Postler TS, Peng V, Bhatt DM, et al. Metformin selectively dampens the acute inflammatory response through an AMPK-dependent mechanism. Sci Rep. 2021;11(1):18721.
  • Shirooie S, Esmaeili J, Sureda A, et al. Evaluation of the effects of metformin administration on morphine tolerance in mice. Neurosci Lett. 2020;716:134638.
  • Pan Y, Sun X, Jiang L, et al. Metformin reduces morphine tolerance by inhibiting microglial-mediated neuroinflammation. J Neuroinflamm. 2016;13(1):294.
  • Shirooie S, Sahebgharani M, Esmaeili J, et al. In vitro evaluation of effects of metformin on morphine and methadone tolerance through mammalian target of rapamycin signaling pathway. J Cell Physiol. 2019;234(3):3058–3066.
  • Oppong-Damoah A, Gannon BM, Murnane KS. The endocannabinoid system and alcohol dependence: will cannabinoid receptor 2 agonism be more fruitful than cannabinoid receptor 1 antagonism? CNS Neurol Disord Drug Targets. 2022;21(1):3–13.
  • Ma C, Zhang M, Liu L, et al. Low-dose cannabinoid receptor 2 agonist induces microglial activation in a cancer pain-morphine tolerance rat model. Life Sci. 2021;264:118635.
  • Kong Q, Tian S, Ma C, et al. Cannabinoid receptor type 2 agonist reduces morphine tolerance via mitogen activated protein kinase phosphatase induction and mitogen activated protein kinase dephosphorylation. Neuroscience. 2022;480:56–64.
  • Iyer V, Slivicki RA, Thomaz AC, et al. The cannabinoid CB2 receptor agonist LY2828360 synergizes with morphine to suppress neuropathic nociception and attenuates morphine reward and physical dependence. Eur J Pharmacol. 2020;886:173544.
  • Li AL, Lin X, Dhopeshwarkar AS, et al. Cannabinoid CB2 agonist AM1710 differentially suppresses distinct pathological pain states and attenuates morphine tolerance and withdrawal. Mol Pharmacol. 2019;95(2):155–168.
  • Wang K, Wang Z, Cui R, et al. Polysaccharopeptide from trametes versicolor blocks inflammatory osteoarthritis pain-morphine tolerance effects via activating cannabinoid type 2 receptor. Int J Biol Macromol. 2019;126:805–810.
  • Ozdemir E. The role of the cannabinoid system in opioid analgesia and tolerance. Mini Rev Med Chem. 2020;20(10):875–885.
  • Yang X, Wei X, Mu Y, et al. A review of the mechanism of the Central analgesic effect of lidocaine. Medicine (Baltimore). 2020;99(17):e19898.
  • Zhang Y, Tao GJ, Hu L, et al. Lidocaine alleviates morphine tolerance via AMPK-SOCS3-dependent neuroinflammation suppression in the spinal cord. J Neuroinflammation. 2017;14(1):211.
  • McGinley MP, Cohen JA. Sphingosine 1-phosphate receptor modulators in multiple sclerosis and other conditions. Lancet. 2021;398(10306):1184–1194.
  • Jozefczuk E, Guzik TJ, Siedlinski M. Significance of sphingosine-1-phosphate in cardiovascular physiology and pathology. Pharmacol Res. 2020;156:104793.
  • Lu S, She M, Zeng Q, et al. Sphingosine 1-phosphate and its receptors in ischemia. Clin Chim Acta. 2021;521:25–33.
  • Doyle TM, Janes K, Chen Z, et al. Activation of sphingosine-1-phosphate receptor subtype 1 in the Central nervous system contributes to morphine-induced hyperalgesia and antinociceptive tolerance in rodents. Pain. 2020;161(9):2107–2118.
  • Kennedy DO. B vitamins and the brain: mechanisms, dose and efficacy–a review. Nutrients. 2016;8(2):68.
  • Deng XT, Han Y, Liu WT, et al. B vitamins potentiate acute morphine antinociception and attenuate the development of tolerance to chronic morphine in mice. Pain Med. 2017;18(10):1961–1974.
  • Ghazanfari S, Imenshahidi M, Etemad L, et al. Effect of cyanocobalamin (vitamin B12) in the induction and expression of morphine tolerance and dependence in mice. Drug Res (Stuttg). 2014;64(3):113–117.
  • Zammel N, Saeed M, Bouali N, et al. Antioxidant and anti-Inflammatory effects of zingiber officinale roscoe and allium subhirsutum: in silico, biochemical and histological study. Foods. 2021;10(6):1383.
  • Pereira MM, Haniadka R, Chacko PP, et al. Zingiber officinale roscoe (ginger) as an adjuvant in cancer treatment: a review. J Buon. 2011;16(3):414–424.
  • Darvishzadeh-Mahani F, Esmaeili-Mahani S, Komeili G, et al. Ginger (zingiber officinale roscoe) prevents the development of morphine analgesic tolerance and physical dependence in rats. J Ethnopharmacol. 2012;141(3):901–907.
  • Torkzadeh-Mahani S, Esmaeili-Mahani S, Nasri S, et al. Ginger extract reduces chronic Morphine-Induced neuroinflammation and glial activation in nucleus accumbens of rats. Addict Health. 2019;11(2):66–72.
  • Jiang C, Xu L, Chen L, et al. Selective suppression of microglial activation by paeoniflorin attenuates morphine tolerance. Eur J Pain. 2015;19(7):908–919.
  • Cai Y, Kong H, Pan YB, et al. Procyanidins alleviates morphine tolerance by inhibiting activation of NLRP3 inflammasome in microglia. J Neuroinflammation. 2016;13(1):53.
  • Meng T, Xiao D, Muhammed A, et al. Anti-Inflammatory action and mechanisms of resveratrol. Molecules. 2021;26(1):229.
  • Han Y, Jiang C, Tang J, et al. Resveratrol reduces morphine tolerance by inhibiting microglial activation via AMPK signalling. Eur J Pain. 2014;18(10):1458–1470.
  • He X, Ou P, Wu K, et al. Resveratrol attenuates morphine antinociceptive tolerance via SIRT1 regulation in the rat spinal cord. Neurosci Lett. 2014;566:55–60.
  • Tsai RY, Wang JC, Chou KY, et al. Resveratrol reverses morphine-induced neuroinflammation in morphine-tolerant rats by reversal HDAC1 expression. J Formos Med Assoc. 2016;115(6):445–454.
  • Liu W, Zhang Y, Zhu W, et al. Sinomenine inhibits the progression of rheumatoid arthritis by regulating the secretion of inflammatory cytokines and monocyte/macrophage subsets. Front Immunol. 2018;9:2228.
  • Wang X, Liu Y, Zhang H, et al. Sinomenine alleviates dorsal root ganglia inflammation to inhibit neuropathic pain via the p38 MAPK/CREB signalling pathway. Eur J Pharmacol. 2021;897:173945.
  • Mena-Valdés LC, Blanco-Hernández Y, Espinosa-Juárez JV, et al. Haloperidol potentiates antinociceptive effects of morphine and disrupt opioid tolerance. Eur J Pharmacol. 2021;893:173825.
  • Ohashi Y, Sakhri FZ, Ikemoto H, et al. Yokukansan inhibits the development of morphine tolerance by regulating presynaptic proteins in DRG neurons. Front Pharmacol. 2022;13:862539.
  • Esmaili-Shahzade-Ali-Akbari P, Hosseinzadeh H, Mehri S. Effect of suvorexant on morphine tolerance and dependence in mice: role of NMDA, AMPA, ERK and CREB proteins. Neurotoxicology. 2021;84:64–72.
  • de Corde-Skurska A, Krzascik P, Lesniak A, et al. Disulfiram abrogates morphine Tolerance-A possible role of µ-Opioid Receptor-Related G-Protein activation in the striatum. IJMS. 2021;22(8):4057.
  • Baser T, Ozdemir E, Filiz AK, et al. Ghrelin receptor agonist hexarelin attenuates antinociceptive tolerance to morphine in rats. Can J Physiol Pharmacol. 2021;99(5):461–467.
  • Liu Q, Su LY, Sun C, et al. Melatonin alleviates morphine analgesic tolerance in mice by decreasing NLRP3 inflammasome activation. Redox Biol. 2020;34:101560.
  • Zhu QM, Wu LX, Zhang B, et al. Donepezil prevents morphine tolerance by regulating N-methyl-d-aspartate receptor, protein kinase C and CaM-dependent kinase II expression in rats. Pharmacol Biochem Behav. 2021;206:173209.
  • Alhassen L, Nuseir K, Ha A, et al. The extract of corydalis yanhusuo prevents morphine tolerance and dependence. Pharmaceuticals (Basel. 2021;14(10):1034. ).
  • Taskiran AS, Avci O. Effect of captopril, an angiotensin-converting enzyme inhibitor, on morphine analgesia and tolerance in rats, and elucidating the inflammation and endoplasmic reticulum stress pathway in this effect. Neurosci Lett. 2021;741:135504.
  • Alifarsangi A, Esmaeili-Mahani S, Sheibani V, et al. The citrus flavanone naringenin prevents the development of morphine analgesic tolerance and conditioned place preference in male rats. Am J Drug Alcohol Abuse. 2021;47(1):43–51.
  • Mai JZ, Liu C, Huang Z, et al. Oral application of bulleyaconitine a attenuates morphine tolerance in neuropathic rats by inhibiting long-term potentiation at C-fiber synapses and protein kinase C gamma in spinal dorsal horn. Mol Pain. 2020;16:1744806920917242.
  • Han D, Dong W, Jiang W. Pinocembrin alleviates chronic morphine-induced analgesic tolerance and hyperalgesia by inhibiting microglial activation. Neurol Res. 2022;15:1–10.

Reprints and Corporate Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

To request a reprint or corporate permissions for this article, please click on the relevant link below:

Academic Permissions

Please note: Selecting permissions does not provide access to the full text of the article, please see our help page How do I view content?

Obtain permissions instantly via Rightslink by clicking on the button below:

If you are unable to obtain permissions via Rightslink, please complete and submit this Permissions form. For more information, please visit our Permissions help page.