{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,8,17]],"date-time":"2026-08-17T20:20:42Z","timestamp":1786998042419,"version":"build-2736575974"},"reference-count":67,"publisher":"MDPI AG","issue":"1","license":[{"start":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T00:00:00Z","timestamp":1609372800000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"funder":[{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07145"],"award-info":[{"award-number":["20K07145"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]},{"DOI":"10.13039\/501100001691","name":"Japan Society for the Promotion of Science","doi-asserted-by":"publisher","award":["20K07168"],"award-info":[{"award-number":["20K07168"]}],"id":[{"id":"10.13039\/501100001691","id-type":"DOI","asserted-by":"publisher"}]}],"content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Pharmaceuticals"],"abstract":"<jats:p>Chemotherapy-induced peripheral neuropathy is a common factor in limiting therapy which can result in therapy cessation or dose reduction. Gabapentin, a calcium channel inhibitor, and duloxetine, a serotonin noradrenaline reuptake inhibitor, are used to treat a variety of pain conditions such as chronic low back pain, postherpetic neuralgia, and diabetic neuropathy. It has been reported that administration of gabapentin suppressed oxaliplatin- and paclitaxel-induced mechanical hyperalgesia in rats. Moreover, duloxetine has been shown to suppress oxaliplatin-induced cold allodynia in rats. However, the mechanisms by which these drugs prevent oxaliplatin- and paclitaxel-induced neuropathy remain unknown. Behavioral assays were performed using cold plate and the von Frey test. The expression levels of proteins were examined using western blot analysis. In this study, we investigated the mechanisms by which gabapentin and duloxetine prevent oxaliplatin- and paclitaxel-induced neuropathy in mice. We found that gabapentin and duloxetine prevented the development of oxaliplatin- and paclitaxel-induced cold and mechanical allodynia. In addition, our results revealed that gabapentin and duloxetine suppressed extracellular signal-regulated protein kinase 1\/2 (ERK1\/2) phosphorylation in the spinal cord of mice. Moreover, PD0325901 prevented the development of oxaliplatin- and paclitaxel-induced neuropathic-like pain behavior by inhibiting ERK1\/2 activation in the spinal cord of mice. In summary, our findings suggest that gabapentin, duloxetine, and PD0325901 prevent the development of oxaliplatin- and paclitaxel-induced neuropathic-like pain behavior by inhibiting ERK1\/2 phosphorylation in mice. Therefore, inhibiting ERK1\/2 phosphorylation could be an effective preventive strategy against oxaliplatin- and paclitaxel-induced neuropathy.<\/jats:p>","DOI":"10.3390\/ph14010030","type":"journal-article","created":{"date-parts":[[2020,12,31]],"date-time":"2020-12-31T10:10:37Z","timestamp":1609409437000},"page":"30","update-policy":"https:\/\/doi.org\/10.3390\/mdpi_crossmark_policy","source":"Crossref","is-referenced-by-count":17,"title":["Gabapentin and Duloxetine Prevent Oxaliplatin- and Paclitaxel-Induced Peripheral Neuropathy by Inhibiting Extracellular Signal-Regulated Kinase 1\/2 (ERK1\/2) Phosphorylation in Spinal Cords of Mice"],"prefix":"10.3390","volume":"14","author":[{"given":"Natsuki","family":"Kato","sequence":"first","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Keisuke","family":"Tateishi","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Masanobu","family":"Tsubaki","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tomoya","family":"Takeda","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Mikihiro","family":"Matsumoto","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Katsumasa","family":"Tsurushima","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"},{"name":"Department of Pharmacy, Sakai City Medical Center, Sakai 593-8304, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Toshihiko","family":"Ishizaka","sequence":"additional","affiliation":[{"name":"Department of Pharmacy, Sakai City Medical Center, Sakai 593-8304, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"ORCID":"https:\/\/orcid.org\/0000-0002-3408-0462","authenticated-orcid":false,"given":"Shozo","family":"Nishida","sequence":"additional","affiliation":[{"name":"Division of Pharmacotherapy, Kindai University Faculty of Pharmacy, Kowakae, Higashi-Osaka 577-8502, Japan"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1968","published-online":{"date-parts":[[2020,12,31]]},"reference":[{"key":"ref_1","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1007\/BF00684890","article-title":"Phase I study of oxaliplatin in patients with advanced cancer","volume":"25","author":"Extra","year":"1990","journal-title":"Cancer Chemother. Pharmacol."},{"key":"ref_2","doi-asserted-by":"crossref","first-page":"1999","DOI":"10.1007\/s00520-014-2242-z","article-title":"A systematic review on chronic oxaliplatin-induced peripheral neuropathy and the relation with oxaliplatin administration","volume":"22","author":"Beijers","year":"2014","journal-title":"Support. Care Cancer"},{"key":"ref_3","doi-asserted-by":"crossref","first-page":"47","DOI":"10.1023\/A:1005805907311","article-title":"Prospective study of paclitaxel-induced peripheral neuropathy with quantitative sensory testing","volume":"35","author":"Forsyth","year":"1997","journal-title":"J. Neurooncol."},{"key":"ref_4","doi-asserted-by":"crossref","first-page":"3","DOI":"10.1111\/j.1365-2141.2008.07558.x","article-title":"Therapy of chemotherapy-induced peripheral neuropathy","volume":"145","author":"Kaley","year":"2009","journal-title":"Br. J. Haematol."},{"key":"ref_5","doi-asserted-by":"crossref","first-page":"90","DOI":"10.1016\/j.neulet.2014.10.014","article-title":"Chemotherapy-induced peripheral neuropathy: What do we know about mechanisms?","volume":"596","author":"Carozzi","year":"2015","journal-title":"Neurosci. Lett."},{"key":"ref_6","doi-asserted-by":"crossref","first-page":"9","DOI":"10.1007\/PL00007853","article-title":"Chemotherapy-induced peripheral neuropathy","volume":"249","author":"Quasthoff","year":"2002","journal-title":"J. Neurol."},{"key":"ref_7","doi-asserted-by":"crossref","first-page":"1507","DOI":"10.1016\/j.ejca.2008.04.018","article-title":"Chemotherapy-induced peripheral neuropathy: Prevention and treatment strategies","volume":"44","author":"Wolf","year":"2008","journal-title":"Eur. J. Cancer"},{"key":"ref_8","doi-asserted-by":"crossref","first-page":"1636","DOI":"10.1016\/j.pain.2012.04.016","article-title":"Cortical effect of oxaliplatin associated with sustained neuropathic pain: Exacerbation of cortical activity and down-regulation of potassium channel expression in somatosensory cortex","volume":"153","author":"Thibault","year":"2012","journal-title":"Pain"},{"key":"ref_9","doi-asserted-by":"crossref","first-page":"28","DOI":"10.1186\/1744-8069-4-28","article-title":"Activation of Erk in the anterior cingulate cortex during the induction and expression of chronic pain","volume":"4","author":"Wei","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_10","doi-asserted-by":"crossref","first-page":"141","DOI":"10.1016\/j.pain.2009.07.017","article-title":"Supraspinal role of protein kinase C in oxaliplatin-induced neuropathy in rat","volume":"146","author":"Norcini","year":"2009","journal-title":"Pain"},{"key":"ref_11","doi-asserted-by":"crossref","first-page":"255","DOI":"10.1016\/j.bbi.2015.06.003","article-title":"MAPK signaling downstream to TLR4 contributes to paclitaxel-induced peripheral neuropathy","volume":"49","author":"Li","year":"2015","journal-title":"Brain Behav. Immun."},{"key":"ref_12","doi-asserted-by":"crossref","first-page":"299","DOI":"10.1016\/j.tips.2010.04.003","article-title":"Neuropathic and chronic pain stimuli downregulate central mu-opioid and dopaminergic transmission","volume":"31","author":"Niikura","year":"2010","journal-title":"Trends Pharmacol. Sci."},{"key":"ref_13","doi-asserted-by":"crossref","first-page":"1769","DOI":"10.1111\/j.1460-9568.2004.03656.x","article-title":"Brain-derived neurotrophic factor induces NMDA receptor subunit one phosphorylation via ERK and PKC in the rat spinal cord","volume":"20","author":"Slack","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_14","doi-asserted-by":"crossref","first-page":"929","DOI":"10.1016\/0896-6273(95)90183-3","article-title":"Determinants of PKC-dependent modulation of a family of neuronal calcium channels","volume":"4","author":"Stea","year":"1995","journal-title":"Neuron"},{"key":"ref_15","doi-asserted-by":"crossref","first-page":"H3079","DOI":"10.1152\/ajpheart.01261.2006","article-title":"Role of L-type calcium channels and PKC in active tone development in rabbit coronary artery","volume":"292","author":"Cobine","year":"2007","journal-title":"Am. J. Physiol. Heart Circ. Physiol."},{"key":"ref_16","doi-asserted-by":"crossref","first-page":"237","DOI":"10.1007\/s12272-013-0057-y","article-title":"Implications and mechanism of action of gabapentin in neuropathic pain","volume":"36","author":"Kukkar","year":"2013","journal-title":"Arch. Pharm. Res."},{"key":"ref_17","doi-asserted-by":"crossref","first-page":"108","DOI":"10.1016\/j.coph.2005.11.003","article-title":"The mechanisms of action of gabapentin and pregabalin","volume":"6","author":"Sills","year":"2006","journal-title":"Curr. Opin. Pharmacol."},{"key":"ref_18","doi-asserted-by":"crossref","first-page":"253","DOI":"10.1016\/j.pain.2009.06.024","article-title":"Duloxetine, a centrally acting analgesic, in the treatment of patients with osteoarthritis knee pain: A 13-week, randomized, placebo-controlled trial","volume":"146","author":"Chappell","year":"2009","journal-title":"Pain"},{"key":"ref_19","doi-asserted-by":"crossref","first-page":"648","DOI":"10.1111\/j.1526-4637.2010.00836.x","article-title":"Maintenance of effect of duloxetine in patients with chronic low back pain: A 41-week uncontrolled, dose-blinded study","volume":"11","author":"Skljarevski","year":"2010","journal-title":"Pain Med."},{"key":"ref_20","doi-asserted-by":"crossref","first-page":"2481","DOI":"10.2146\/ajhp050006","article-title":"Duloxetine: A balanced and selective norepinephrine- and serotonin-reuptake inhibitor","volume":"62","author":"Westanmo","year":"2005","journal-title":"Am. J. Health Syst. Pharm."},{"key":"ref_21","doi-asserted-by":"crossref","first-page":"1193","DOI":"10.1016\/j.pain.2012.02.021","article-title":"Conditioned pain modulation predicts duloxetine efficacy in painful diabetic neuropathy","volume":"153","author":"Yarnitsky","year":"2012","journal-title":"Pain"},{"key":"ref_22","doi-asserted-by":"crossref","first-page":"292","DOI":"10.1254\/jphs.14058FP","article-title":"Gabapentin prevents oxaliplatin-induced mechanical hyperalgesia in mice","volume":"125","author":"Ohsawa","year":"2014","journal-title":"J. Pharmacol. Sci."},{"key":"ref_23","first-page":"507","article-title":"Therapeutic potential of certain drug combinations on paclitaxel-induced peripheral neuropathy in rats","volume":"58","author":"Ciotu","year":"2017","journal-title":"Rom. J. Morphol. Embryol."},{"key":"ref_24","doi-asserted-by":"crossref","unstructured":"Kim, W., Chung, Y., Choi, S., Min, B.I., and Kim, S.K. (2017). Duloxetine Protects against Oxaliplatin-Induced Neuropathic Pain and Spinal Neuron Hyperexcitability in Rodents. Int. J. Mol. Sci., 18.","DOI":"10.3390\/ijms18122626"},{"key":"ref_25","first-page":"1239","article-title":"Trametinib suppresses chemotherapy-induced cold and mechanical allodynia via inhibition of extracellular-regulated protein kinase 1\/2 activation","volume":"8","author":"Tsubaki","year":"2018","journal-title":"Am. J. Cancer Res."},{"key":"ref_26","doi-asserted-by":"crossref","first-page":"131","DOI":"10.1016\/j.jphs.2019.10.005","article-title":"Improvement of peripheral vascular impairment by a phosphodiesterase type 5 inhibitor tadalafil prevents oxaliplatin-induced peripheral neuropathy in mice","volume":"141","author":"Ogihara","year":"2019","journal-title":"J. Pharmacol. Sci."},{"key":"ref_27","doi-asserted-by":"crossref","unstructured":"Li, D., Lee, J.H., Choi, C.W., Kim, J., Kim, S.K., and Kim, W. (2019). The Analgesic Effect of Venlafaxine and Its Mechanism on Oxaliplatin-Induced Neuropathic Pain in Mice. Int. J. Mol. Sci., 20.","DOI":"10.3390\/ijms20071652"},{"key":"ref_28","doi-asserted-by":"crossref","first-page":"882","DOI":"10.1016\/j.biopha.2019.01.008","article-title":"Interventional and preventive effects of aripiprazole and ceftriaxone used alone or in combination on oxaliplatin-induced tactile and cold allodynia in mice","volume":"111","year":"2019","journal-title":"Biomed. Pharmacother."},{"key":"ref_29","doi-asserted-by":"crossref","unstructured":"Kim, W., Kim, M.J., Go, D., Min, B.I., Na, H.S., and Kim, S.K. (2016). Combined Effects of Bee Venom Acupuncture and Morphine on Oxaliplatin-Induced Neuropathic Pain in Mice. Toxins, 8.","DOI":"10.3390\/toxins8020033"},{"key":"ref_30","doi-asserted-by":"crossref","first-page":"469","DOI":"10.1254\/jphs.08325SC","article-title":"Effects of the prostaglandin E1 analog limaprost on mechanical allodynia caused by chemotherapeutic agents in mice","volume":"109","author":"Gauchan","year":"2009","journal-title":"J. Pharmacol. Sci."},{"key":"ref_31","doi-asserted-by":"crossref","first-page":"2777","DOI":"10.1007\/s00213-020-05572-2","article-title":"Kappa opioid receptors mediate an initial aversive component of paclitaxel-induced neuropathy","volume":"237","author":"Meade","year":"2020","journal-title":"Psychopharmacology"},{"key":"ref_32","doi-asserted-by":"crossref","first-page":"100037","DOI":"10.1016\/j.ynpai.2019.100037","article-title":"Alleviation of paclitaxel-induced mechanical hypersensitivity and hyperalgesic priming with AMPK activators in male and female mice","volume":"6","author":"Inyang","year":"2019","journal-title":"Neurobiol. Pain"},{"key":"ref_33","doi-asserted-by":"crossref","first-page":"761","DOI":"10.1007\/s11418-019-01327-2","article-title":"Search of anti-allodynic compounds from Plantaginis Semen, a crude drug ingredient of Kampo formula \u201cGoshajinkigan\u201d","volume":"73","author":"Toume","year":"2019","journal-title":"J. Nat. Med."},{"key":"ref_34","doi-asserted-by":"crossref","first-page":"163","DOI":"10.1016\/j.neuropharm.2018.11.027","article-title":"Mechanical allodynia and enhanced responses to capsaicin are mediated by PI3K in a paclitaxel model of peripheral neuropathy","volume":"146","author":"Adamek","year":"2019","journal-title":"Neuropharmacology"},{"key":"ref_35","doi-asserted-by":"crossref","first-page":"159","DOI":"10.1016\/j.imr.2018.03.006","article-title":"Effect of certain trimethoxy flavones on paclitaxel-induced peripheral neuropathy in mice","volume":"7","author":"Nadipelly","year":"2018","journal-title":"Integr. Med. Res."},{"key":"ref_36","doi-asserted-by":"crossref","first-page":"659","DOI":"10.3389\/fphar.2019.00659","article-title":"Anti-Inflammatory and Anti-Arthritic Efficacies of an Indian Traditional Herbo-Mineral Medicine \u201cDivya Amvatari Ras\u201d in Collagen Antibody-Induced Arthritis (CAIA) Mouse Model Through Modulation of IL-6\/IL-1\u03b2\/TNF-\u03b1\/NF\u03baB Signaling","volume":"10","author":"Balkrishna","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_37","doi-asserted-by":"crossref","first-page":"27","DOI":"10.4103\/0976-0105.177703","article-title":"A simple practice guide for dose conversion between animals and human","volume":"7","author":"Nair","year":"2016","journal-title":"J. Basic Clin. Pharm."},{"key":"ref_38","doi-asserted-by":"crossref","first-page":"146","DOI":"10.1159\/000443898","article-title":"Altered Expression of Cytoskeletal and Axonal Proteins in Oxaliplatin-Induced Neuropathy","volume":"97","author":"Sanna","year":"2016","journal-title":"Pharmacology"},{"key":"ref_39","doi-asserted-by":"crossref","first-page":"4614","DOI":"10.1523\/JNEUROSCI.1580-14.2015","article-title":"Nociceptor beta II, delta, and epsilon isoforms of PKC differentially mediate paclitaxel-induced spontaneous and evoked pain","volume":"35","author":"He","year":"2015","journal-title":"J. Neurosci."},{"key":"ref_40","doi-asserted-by":"crossref","first-page":"507","DOI":"10.1016\/S0306-4522(01)00425-0","article-title":"Role of protein kinase Cepsilon and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat","volume":"108","author":"Dina","year":"2001","journal-title":"Neuroscience"},{"key":"ref_41","doi-asserted-by":"crossref","first-page":"19364","DOI":"10.1074\/jbc.M116.732347","article-title":"Presynaptic N-Methyl-d-aspartate (NMDA) Receptor Activity Is Increased Through Protein Kinase C in Paclitaxel-induced Neuropathic Pain","volume":"291","author":"Xie","year":"2016","journal-title":"J. Biol. Chem."},{"key":"ref_42","doi-asserted-by":"crossref","first-page":"26","DOI":"10.1186\/1744-8069-4-26","article-title":"PKA and ERK, but not PKC, in the amygdala contribute to pain-related synaptic plasticity and behavior","volume":"4","author":"Fu","year":"2008","journal-title":"Mol. Pain"},{"key":"ref_43","doi-asserted-by":"crossref","first-page":"2881","DOI":"10.1111\/j.1460-9568.2004.03754.x","article-title":"Differential activation of MAPK in injured and uninjured DRG neurons following chronic constriction injury of the sciatic nerve in rats","volume":"20","author":"Obata","year":"2004","journal-title":"Eur. J. Neurosci."},{"key":"ref_44","doi-asserted-by":"crossref","first-page":"478","DOI":"10.1523\/JNEUROSCI.22-02-00478.2002","article-title":"ERK MAP kinase activation in superficial spinal cord neurons induces prodynorphin and NK-1 upregulation and contributes to persistent inflammatory pain hypersensitivity","volume":"22","author":"Ji","year":"2002","journal-title":"J. Neurosci."},{"key":"ref_45","doi-asserted-by":"crossref","first-page":"135","DOI":"10.1016\/j.brainresrev.2008.12.011","article-title":"MAP kinase and pain","volume":"60","author":"Ji","year":"2009","journal-title":"Brain Res. Rev."},{"key":"ref_46","doi-asserted-by":"crossref","first-page":"699","DOI":"10.1517\/14728222.9.4.699","article-title":"The ERK\/MAPK pathway, as a target for the treatment of neuropathic pain","volume":"9","author":"Ma","year":"2005","journal-title":"Expert Opin. Ther. Targets"},{"key":"ref_47","doi-asserted-by":"crossref","first-page":"50","DOI":"10.1016\/j.brainres.2009.01.052","article-title":"Activation of ERK in the locus coeruleus following acute noxious stimulation","volume":"1263","author":"Imbe","year":"2009","journal-title":"Brain Res."},{"key":"ref_48","doi-asserted-by":"crossref","first-page":"244","DOI":"10.1016\/j.joca.2008.06.015","article-title":"Vanilloid receptor TRPV1-mediated phosphorylation of ERK in murine adjuvant arthritis","volume":"17","author":"Chen","year":"2009","journal-title":"Osteoarthr. Cartil."},{"key":"ref_49","doi-asserted-by":"crossref","first-page":"61","DOI":"10.1016\/j.ejphar.2013.03.003","article-title":"Targeting TRP channels for pain relief","volume":"716","author":"Brederson","year":"2013","journal-title":"Eur. J. Pharmacol."},{"key":"ref_50","doi-asserted-by":"crossref","first-page":"437","DOI":"10.1007\/s00424-010-0788-2","article-title":"Transient receptor potential channelopathies","volume":"460","author":"Nilius","year":"2010","journal-title":"Pflug. Arch."},{"key":"ref_51","doi-asserted-by":"crossref","first-page":"405","DOI":"10.1097\/j.pain.0000000000001722","article-title":"Oxaliplatin-induced neuropathy occurs through impairment of haemoglobin proton buffering and is reversed by carbonic anhydrase inhibitors","volume":"161","author":"Potenzieri","year":"2020","journal-title":"Pain"},{"key":"ref_52","doi-asserted-by":"crossref","first-page":"30","DOI":"10.1016\/j.jtcme.2016.01.003","article-title":"Shakuyakukanzoto attenuates oxaliplatin-induced cold dysesthesia by inhibiting the expression of transient receptor potential melastatin 8 in mice","volume":"7","author":"Andoh","year":"2016","journal-title":"J. Tradit. Complement. Med."},{"key":"ref_53","doi-asserted-by":"crossref","first-page":"1040","DOI":"10.3389\/fphys.2017.01040","article-title":"Thermo-Sensitive TRP Channels: Novel Targets for Treating Chemotherapy-Induced Peripheral Pain","volume":"8","author":"Braidy","year":"2017","journal-title":"Front. Physiol."},{"key":"ref_54","doi-asserted-by":"crossref","unstructured":"Kamata, Y., Kambe, T., Chiba, T., Yamamoto, K., Kawakami, K., Abe, K., and Taguchi, K. (2020). Paclitaxel Induces Upregulation of Transient Receptor Potential Vanilloid 1 Expression in the Rat Spinal Cord. Int. J. Mol. Sci., 21.","DOI":"10.3390\/ijms21124341"},{"key":"ref_55","doi-asserted-by":"crossref","first-page":"76","DOI":"10.1016\/j.biopha.2018.09.018","article-title":"Cinobufacini protects against paclitaxel-induced peripheral neuropathic pain and suppresses TRPV1 up-regulation and spinal astrocyte activation in rats","volume":"108","author":"Ba","year":"2018","journal-title":"Biomed. Pharmacother."},{"key":"ref_56","doi-asserted-by":"crossref","first-page":"64","DOI":"10.1016\/j.expneurol.2018.04.014","article-title":"TRPV4 inhibition prevents paclitaxel-induced neurotoxicity in preclinical models","volume":"306","author":"Boehmerle","year":"2018","journal-title":"Exp. Neurol."},{"key":"ref_57","doi-asserted-by":"crossref","first-page":"214","DOI":"10.1016\/j.neuroscience.2018.01.049","article-title":"Long Non-coding RNA BC168687 is Involved in TRPV1-mediated Diabetic Neuropathic Pain in Rats","volume":"374","author":"Liu","year":"2018","journal-title":"Neuroscience"},{"key":"ref_58","doi-asserted-by":"crossref","first-page":"285","DOI":"10.3389\/fphys.2019.00285","article-title":"Transient Receptor Potential Melastatin 8 (TRPM8)-Based Mechanisms Underlie Both the Cold Temperature-Induced Inflammatory Reactions and the Synergistic Effect of Cigarette Smoke in Human Bronchial Epithelial (16HBE) Cells","volume":"10","author":"Wang","year":"2019","journal-title":"Front. Physiol."},{"key":"ref_59","doi-asserted-by":"crossref","first-page":"196","DOI":"10.1016\/j.neulet.2018.10.037","article-title":"Intrathecal administration of adrenomedullin induces mechanical allodynia and neurochemical changes in spinal cord and DRG","volume":"690","author":"Huang","year":"2019","journal-title":"Neurosci. Lett."},{"key":"ref_60","doi-asserted-by":"crossref","first-page":"2769","DOI":"10.1038\/s41598-019-39184-4","article-title":"Silencing of spinal Trpv1 attenuates neuropathic pain in rats by inhibiting CAMKII expression and ERK2 phosphorylation","volume":"9","author":"Guo","year":"2019","journal-title":"Sci. Rep."},{"key":"ref_61","doi-asserted-by":"crossref","first-page":"866","DOI":"10.1007\/s10147-015-0810-y","article-title":"Effect of duloxetine in Japanese patients with chemotherapy-induced peripheral neuropathy: A pilot randomized trial","volume":"20","author":"Hirayama","year":"2015","journal-title":"Int. J. Clin. Oncol."},{"key":"ref_62","doi-asserted-by":"crossref","first-page":"737","DOI":"10.1093\/bja\/aex229","article-title":"Clinical and preclinical perspectives on Chemotherapy-Induced Peripheral Neuropathy (CIPN): A narrative review","volume":"119","author":"Flatters","year":"2017","journal-title":"Br. J. Anaesth."},{"key":"ref_63","doi-asserted-by":"crossref","first-page":"200","DOI":"10.5603\/GP.a2018.0034","article-title":"Effectiveness of gabapentin pharmacotherapy in chemotherapy-induced peripheral neuropathy","volume":"89","author":"Magnowska","year":"2018","journal-title":"Ginekol. Pol."},{"key":"ref_64","doi-asserted-by":"crossref","first-page":"177","DOI":"10.1097\/j.pain.0000000000001697","article-title":"Sexually dimorphic therapeutic response in bortezomib-induced neuropathic pain reveals altered pain physiology in female rodents","volume":"161","author":"Stockstill","year":"2020","journal-title":"Pain"},{"key":"ref_65","doi-asserted-by":"crossref","first-page":"745","DOI":"10.3389\/fphar.2019.00745","article-title":"Resolvin D5 Inhibits Neuropathic and Inflammatory Pain in Male But Not Female Mice: Distinct Actions of D-Series Resolvins in Chemotherapy-Induced Peripheral Neuropathy","volume":"10","author":"Luo","year":"2019","journal-title":"Front. Pharmacol."},{"key":"ref_66","doi-asserted-by":"crossref","unstructured":"Tsubaki, M., Takeda, T., Matsumoto, M., Kato, N., Yasuhara, S., Koumoto, Y.I., Imano, M., Satou, T., and Nishida, S. (2018). Tamoxifen suppresses paclitaxel-, vincristine-, and bortezomib-induced neuropathy via inhibition of the protein kinase C\/extracellular signal-regulated kinase pathway. Tumour Biol., 40.","DOI":"10.1177\/1010428318808670"},{"key":"ref_67","doi-asserted-by":"crossref","first-page":"243","DOI":"10.1002\/ijc.29367","article-title":"PKC\/MEK inhibitors suppress oxaliplatin-induced neuropathy and potentiate the antitumor effects","volume":"37","author":"Tsubaki","year":"2015","journal-title":"Int. J. Cancer"}],"container-title":["Pharmaceuticals"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/1\/30\/pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,10,11]],"date-time":"2025-10-11T10:48:29Z","timestamp":1760179709000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.mdpi.com\/1424-8247\/14\/1\/30"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2020,12,31]]},"references-count":67,"journal-issue":{"issue":"1","published-online":{"date-parts":[[2021,1]]}},"alternative-id":["ph14010030"],"URL":"https:\/\/doi.org\/10.3390\/ph14010030","relation":{},"ISSN":["1424-8247"],"issn-type":[{"value":"1424-8247","type":"electronic"}],"subject":[],"published":{"date-parts":[[2020,12,31]]}}}