{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,11,1]],"date-time":"2026-11-01T00:31:53Z","timestamp":1793493113981,"version":"4.5.0"},"reference-count":70,"publisher":"Frontiers Media SA","license":[{"start":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T00:00:00Z","timestamp":1751414400000},"content-version":"vor","delay-in-days":0,"URL":"https:\/\/creativecommons.org\/licenses\/by\/4.0\/"}],"content-domain":{"domain":["frontiersin.org"],"crossmark-restriction":true},"short-container-title":["Front. Neurosci."],"abstract":"<jats:sec>\n                    <jats:title>Introduction<\/jats:title>\n                    <jats:p>\n                      As a taxane-based cytostatic agent, paclitaxel holds a broad spectrum of life-saving properties. However, its use is frequently limited by painful neuropathy in the extremities, which severely hinders the ultimate prognosis of cancer survivors. While bee venom therapy has shown promise in alleviating chemotherapy-induced neuropathic pain, the analgesic potential of its primary bioactive components, such as melittin and phospholipase A2 (bvPLA2), remains uncharacterized. This study investigated the ameliorative effects of melittin against paclitaxel-induced peripheral neuropathy in rats through integrated behavioral,\n                      <jats:italic>in vivo<\/jats:italic>\n                      electrophysiological, and neuropharmacological approaches.\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Methods<\/jats:title>\n                    <jats:p>\n                      Paclitaxel was administered intraperitoneally (i.p.) at a total dose of 8 mg\/kg. Cold and mechanical allodynia and hyperalgesia were quantified using the acetone drop and von Frey filament tests. To compare the therapeutic properties of bee venom ingredients, either melittin (0.5 mg\/kg) or bvPLA2 (0.12 mg\/kg) was administered subcutaneously at ST36 (Zusanli acupoint).\n                      <jats:italic>In vivo<\/jats:italic>\n                      extracellular recordings of wide dynamic range (WDR) neurons were performed in the spinal dorsal horn. Noradrenaline depletion was induced by the i.p. treatment with N-(2-Chloroethyl)-N-ethyl-2-bromobenzylamine (DSP-4, 50 mg\/kg), and serotonin depletion was conducted by the i.p. administration of para-chlorophenylalanine (PCPA, 450 mg\/kg).\n                    <\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Results<\/jats:title>\n                    <jats:p>ST36 treatment with melittin, but not bvPLA2, markedly impeded mechanical and cold hypersensitivity. Electrophysiological analysis revealed that paclitaxel induced spontaneous and stimulus-evoked hyperexcitation of spinal WDR neurons. Melittin selectively suppressed evoked neuronal activities (i.e., acute responses and after-discharges) without modulating the spontaneous firing of WDR neurons. Neuropharmacological investigation demonstrated that the effects of melittin were fully reversed by noradrenaline depletion, whereas serotonin depletion had no effect.<\/jats:p>\n                  <\/jats:sec>\n                  <jats:sec>\n                    <jats:title>Discussion<\/jats:title>\n                    <jats:p>Our findings establish that melittin treatment at ST36 could ease paclitaxel-induced neuropathic pain by partially attenuating the hyperexcitable state of spinal WDR neurons. Furthermore, these ameliorative actions were mediated by the specific recruitment of the endogenous noradrenergic system. This study provides novel evidence supporting melittin as a targeted symptomatic agent for paclitaxel-induced peripheral neuropathy, which would advance the development of promising analgesic strategies in oncological care.<\/jats:p>\n                  <\/jats:sec>","DOI":"10.3389\/fnins.2025.1622553","type":"journal-article","created":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T01:52:09Z","timestamp":1751421129000},"update-policy":"https:\/\/doi.org\/10.3389\/crossmark-policy","source":"Crossref","is-referenced-by-count":5,"title":["Therapeutic effects of melittin on paclitaxel-induced peripheral neuropathic pain and spinal neuronal hyperactivity in male rats"],"prefix":"10.3389","volume":"19","author":[{"given":"Daxian","family":"Li","sequence":"first","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yan","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Lirong","family":"Chang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yizhi","family":"Song","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Xiaoqiang","family":"Du","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fenqin","family":"Xue","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yang","family":"Liu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Jie","family":"Wu","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Tianlong","family":"Wang","sequence":"additional","affiliation":[],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"1965","published-online":{"date-parts":[[2025,7,2]]},"reference":[{"key":"B1","doi-asserted-by":"publisher","first-page":"807","DOI":"10.1016\/S1474-4422(10)70143-5","article-title":"Neuropathic pain: diagnosis, pathophysiological mechanisms, and treatment","volume":"9","author":"Baron","year":"2010","journal-title":"Lancet Neurol."},{"key":"B2","doi-asserted-by":"publisher","first-page":"1505","DOI":"10.1097\/j.pain.0000000000001547","article-title":"Preventive hypothermia as a neuroprotective strategy for paclitaxel-induced peripheral neuropathy","volume":"160","author":"Beh","year":"2019","journal-title":"Pain"},{"key":"B3","doi-asserted-by":"publisher","first-page":"363","DOI":"10.2217\/pmt-2018-0020","article-title":"An updated understanding of the mechanisms involved in chemotherapy-induced neuropathy","volume":"8","author":"Boyette-Davis","year":"2018","journal-title":"Pain Manag."},{"key":"B4","doi-asserted-by":"publisher","first-page":"285","DOI":"10.2217\/pmt.15.19","article-title":"Mechanisms involved in the development of chemotherapy-induced neuropathy","volume":"5","author":"Boyette-Davis","year":"2015","journal-title":"Pain Manag."},{"key":"B5","doi-asserted-by":"publisher","first-page":"500","DOI":"10.1097\/WCO.0000000000000234","article-title":"Chemotherapy-induced peripheral neurotoxicity","volume":"28","author":"Cavaletti","year":"2015","journal-title":"Curr. Opin. Neurol."},{"key":"B6","doi-asserted-by":"publisher","first-page":"432","DOI":"10.3390\/nu11020432","article-title":"Phytochemicals of cinnamomi cortex: cinnamic acid, but not cinnamaldehyde, attenuates oxaliplatin-induced cold and mechanical hypersensitivity in rats","volume":"11","author":"Chae","year":"2019","journal-title":"Nutrients"},{"key":"B7","doi-asserted-by":"publisher","first-page":"696","DOI":"10.1124\/jpet.105.091314","article-title":"Effect of morphine on deep dorsal horn projection neurons depends on spinal GABAergic and glycinergic tone: implications for reduced opioid effect in neuropathic pain","volume":"315","author":"Chen","year":"2005","journal-title":"J. Pharmacol. Exp. Ther."},{"key":"B8","doi-asserted-by":"publisher","first-page":"396","DOI":"10.3390\/toxins11070396","article-title":"Analgesic effect of melittin on oxaliplatin-induced peripheral neuropathy in rats","volume":"11","author":"Choi","year":"2019","journal-title":"Toxins"},{"key":"B9","doi-asserted-by":"publisher","first-page":"431","DOI":"10.1007\/s12576-016-0505-9","article-title":"Noradrenergic inhibition of spinal hyperexcitation elicited by cutaneous cold stimuli in rats with oxaliplatin-induced allodynia: electrophysiological and behavioral assessments","volume":"67","author":"Choi","year":"2017","journal-title":"J. Physiol. Sci."},{"key":"B10","doi-asserted-by":"publisher","first-page":"150","DOI":"10.1016\/j.pain.2004.01.029","article-title":"Ethosuximide reverses paclitaxel- and vincristine-induced painful peripheral neuropathy","volume":"109","author":"Flatters","year":"2004","journal-title":"Pain"},{"key":"B11","doi-asserted-by":"publisher","first-page":"219","DOI":"10.1016\/j.neulet.2005.12.013","article-title":"Acetyl-L-carnitine prevents and reduces paclitaxel-induced painful peripheral neuropathy","volume":"397","author":"Flatters","year":"2006","journal-title":"Neurosci. Lett."},{"key":"B12","doi-asserted-by":"publisher","first-page":"529","DOI":"10.1111\/j.1469-7793.1999.00529.x","article-title":"Responsiveness of rat substantia gelatinosa neurones to mechanical but not thermal stimuli revealed by in vivo patch-clamp recording","volume":"521","author":"Furue","year":"1999","journal-title":"J. Physiol."},{"key":"B13","doi-asserted-by":"publisher","first-page":"117","DOI":"10.3390\/toxins16030117","article-title":"Bee venom: composition and anticancer properties","volume":"16","author":"Gajski","year":"2024","journal-title":"Toxins"},{"key":"B14","doi-asserted-by":"publisher","first-page":"1084","DOI":"10.1016\/S1474-4422(13)70193-5","article-title":"Combination pharmacotherapy for management of chronic pain: from bench to bedside","volume":"12","author":"Gilron","year":"2013","journal-title":"Lancet Neurol."},{"key":"B15","doi-asserted-by":"publisher","first-page":"202","DOI":"10.1007\/BF00258116","article-title":"Inhibition of growth of leukemic cells by inhibitors of calmodulin: phenothiazines and melittin","volume":"14","author":"Hait","year":"1985","journal-title":"Cancer Chemother. Pharmacol."},{"key":"B16","doi-asserted-by":"publisher","first-page":"e421","DOI":"10.1200\/JOP.2014.001776","article-title":"Prevention and management of chemotherapy-induced peripheral neuropathy in survivors of adult cancers: American Society of Clinical Oncology Clinical Practice Guideline Summary","volume":"10","author":"Hershman","year":"2014","journal-title":"J. Oncol. Pract."},{"key":"B17","doi-asserted-by":"publisher","first-page":"4148","DOI":"10.1523\/JNEUROSCI.4835-13.2014","article-title":"Optoactivation of locus ceruleus neurons evokes bidirectional changes in thermal nociception in rats","volume":"34","author":"Hickey","year":"2014","journal-title":"J. Neurosci."},{"key":"B18","doi-asserted-by":"publisher","first-page":"513","DOI":"10.1016\/0006-8993(80)90049-9","article-title":"DSP-4: a novel compound with neurotoxic effects on noradrenergic neurons of adult and developing rats","volume":"188","author":"Jaim-Etcheverry","year":"1980","journal-title":"Brain Res."},{"key":"B19","doi-asserted-by":"publisher","first-page":"8733","DOI":"10.3390\/ijms22168733","article-title":"Preclinical and clinical evidence of therapeutic agents for paclitaxel-induced peripheral neuropathy","volume":"22","author":"Kawashiri","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B20","doi-asserted-by":"publisher","first-page":"183","DOI":"10.1016\/j.phrs.2004.07.011","article-title":"Antinociceptive mechanisms associated with diluted bee venom acupuncture (apipuncture) in the rat formalin test: involvement of descending adrenergic and serotonergic pathways","volume":"51","author":"Kim","year":"2005","journal-title":"Pharmacol. Res."},{"key":"B21","doi-asserted-by":"publisher","first-page":"2283","DOI":"10.3390\/plants12122283","article-title":"Magnolin inhibits paclitaxel-induced cold allodynia and ERK1\/2 activation in mice","volume":"12","author":"Kim","year":"2023","journal-title":"Plants"},{"key":"B22","doi-asserted-by":"publisher","first-page":"2626","DOI":"10.3390\/ijms18122626","article-title":"Duloxetine protects against oxaliplatin-induced neuropathic pain and spinal neuron hyperexcitability in rodents","volume":"18","author":"Kim","year":"2017","journal-title":"Int. J. Mol. Sci."},{"key":"B23","doi-asserted-by":"publisher","first-page":"33","DOI":"10.3390\/toxins8020033","article-title":"Combined effects of bee venom acupuncture and morphine on oxaliplatin-induced neuropathic pain in mice","volume":"8","author":"Kim","year":"2016","journal-title":"Toxins"},{"key":"B24","doi-asserted-by":"publisher","first-page":"271","DOI":"10.1016\/S0304-3959(00)00412-7","article-title":"Bee venom injection into an acupuncture point reduces arthritis associated edema and nociceptive responses","volume":"90","author":"Kwon","year":"2001","journal-title":"Pain"},{"key":"B25","doi-asserted-by":"publisher","first-page":"895","DOI":"10.1016\/j.jpain.2009.06.012","article-title":"Central sensitization: a generator of pain hypersensitivity by central neural plasticity","volume":"10","author":"Latremoliere","year":"2009","journal-title":"J. Pain"},{"key":"B26","doi-asserted-by":"publisher","first-page":"718","DOI":"10.3390\/cimb44020050","article-title":"Analgesic effect of SH003 and trichosanthes kirilowii maximowicz in paclitaxel-induced neuropathic pain in mice","volume":"44","author":"Lee","year":"2022","journal-title":"Curr. Issues Mol. Biol."},{"key":"B27","doi-asserted-by":"publisher","first-page":"251","DOI":"10.1292\/jvms.63.251","article-title":"Bee venom pretreatment has both an antinociceptive and anti-inflammatory effect on carrageenan-induced inflammation","volume":"63","author":"Lee","year":"2001","journal-title":"J. Vet. Med. Sci."},{"key":"B28","doi-asserted-by":"publisher","first-page":"775","DOI":"10.3390\/toxins12120775","article-title":"The involvement of central noradrenergic pathway in the analgesic effect of bee venom acupuncture on vincristine-induced peripheral neuropathy in rats","volume":"12","author":"Li","year":"","journal-title":"Toxins"},{"key":"B29","doi-asserted-by":"publisher","first-page":"1652","DOI":"10.3390\/ijms20071652","article-title":"The analgesic effect of venlafaxine and its mechanism on oxaliplatin-induced neuropathic pain in mice","volume":"20","author":"Li","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B30","doi-asserted-by":"publisher","first-page":"2422","DOI":"10.3390\/toxins7072422","article-title":"Analgesic effects of bee venom derived phospholipase A(2) in a mouse model of oxaliplatin-induced neuropathic pain","volume":"7","author":"Li","year":"2015","journal-title":"Toxins"},{"key":"B31","doi-asserted-by":"publisher","first-page":"489","DOI":"10.4196\/kjpp.2021.25.5.489","article-title":"5-HT(1A) receptors mediate the analgesic effect of rosavin in a mouse model of oxaliplatin-induced peripheral neuropathic pain","volume":"25","author":"Li","year":"2021","journal-title":"Korean J. Physiol. Pharmacol."},{"key":"B32","doi-asserted-by":"publisher","first-page":"620","DOI":"10.3390\/toxins12100620","article-title":"Long-lasting and additive analgesic effects of combined treatment of bee venom acupuncture and venlafaxine on paclitaxel-induced allodynia in mice","volume":"12","author":"Li","year":"","journal-title":"Toxins"},{"key":"B33","doi-asserted-by":"publisher","first-page":"618","DOI":"10.3390\/toxins12100618","article-title":"Clinical applications of bee venom acupoint injection","volume":"12","author":"Lin","year":"2020","journal-title":"Toxins"},{"key":"B34","doi-asserted-by":"publisher","first-page":"22123","DOI":"10.1038\/srep22123","article-title":"Probing the effects and mechanisms of electroacupuncture at ipsilateral or contralateral ST36-ST37 acupoints on CFA-induced inflammatory pain","volume":"6","author":"Lu","year":"2016","journal-title":"Sci. Rep."},{"key":"B35","doi-asserted-by":"publisher","first-page":"1723","DOI":"10.1016\/j.intimp.2005.05.012","article-title":"Effects of central and peripheral depletion of serotonergic system on carrageenan-induced paw oedema","volume":"5","author":"Maleki","year":"2005","journal-title":"Int. Immunopharmacol."},{"key":"B36","doi-asserted-by":"publisher","first-page":"609","DOI":"10.1517\/14740338.6.5.609","article-title":"Paclitaxel: a review of adverse toxicities and novel delivery strategies","volume":"6","author":"Marupudi","year":"2007","journal-title":"Expert Opin. Drug Saf."},{"key":"B37","doi-asserted-by":"publisher","first-page":"1893","DOI":"10.1152\/jn.00325.2018","article-title":"Characterization and pharmacological modulation of noci-responsive deep dorsal horn neurons across diverse rat models of pathological pain","volume":"120","author":"McGaraughty","year":"2018","journal-title":"J. Neurophysiol."},{"key":"B38","doi-asserted-by":"publisher","first-page":"355","DOI":"10.1016\/S0301-0082(02)00009-6","article-title":"Descending control of pain","volume":"66","author":"Millan","year":"2002","journal-title":"Prog. Neurobiol."},{"key":"B39","doi-asserted-by":"publisher","first-page":"3642","DOI":"10.1046\/j.1460-9568.1998.00370.x","article-title":"Nociceptive integration in the rat spinal cord: role of non-linear membrane properties of deep dorsal horn neurons","volume":"10","author":"Morisset","year":"1998","journal-title":"Eur. J. Neurosci."},{"key":"B40","doi-asserted-by":"publisher","first-page":"166","DOI":"10.1177\/1534735411413265","article-title":"Effects of sweet bee venom pharmacopuncture treatment for chemotherapy-induced peripheral neuropathy: a case series","volume":"11","author":"Park","year":"2012","journal-title":"Integr. Cancer Ther."},{"key":"B41","doi-asserted-by":"publisher","first-page":"691","DOI":"10.1016\/0301-0082(93)90011-G","article-title":"Antinociception induced by alpha-2-adrenoceptor agonists, with special emphasis on medetomidine studies","volume":"40","author":"Pertovaara","year":"1993","journal-title":"Prog. Neurobiol."},{"key":"B42","doi-asserted-by":"publisher","first-page":"293","DOI":"10.1016\/S0304-3959(01)00363-3","article-title":"A painful peripheral neuropathy in the rat produced by the chemotherapeutic drug, paclitaxel","volume":"94","author":"Polomano","year":"2001","journal-title":"Pain"},{"key":"B43","doi-asserted-by":"publisher","first-page":"C188","DOI":"10.12968\/hmed.2013.74.Sup12.C188","article-title":"An introduction to pain pathways and mechanisms","volume":"74","author":"Reddi","year":"2013","journal-title":"Br. J. Hosp. Med."},{"key":"B44","doi-asserted-by":"publisher","first-page":"361","DOI":"10.3390\/toxins9110361","article-title":"Efficacy of bee venom acupuncture for chronic low back pain: a randomized, double-blinded, sham-controlled trial","volume":"9","author":"Seo","year":"2017","journal-title":"Toxins"},{"key":"B45","doi-asserted-by":"publisher","first-page":"1744806919840098","DOI":"10.1177\/1744806919840098","article-title":"Peripheral and central oxidative stress in chemotherapy-induced neuropathic pain","volume":"15","author":"Shim","year":"2019","journal-title":"Mol. Pain"},{"key":"B46","doi-asserted-by":"publisher","first-page":"507","DOI":"10.1016\/j.expneurol.2006.05.007","article-title":"Paclitaxel- and vincristine-evoked painful peripheral neuropathies: loss of epidermal innervation and activation of Langerhans cells","volume":"201","author":"Siau","year":"2006","journal-title":"Exp. Neurol."},{"key":"B47","doi-asserted-by":"publisher","first-page":"e13323","DOI":"10.14814\/phy2.13323","article-title":"Sensory processing of deep tissue nociception in the rat spinal cord and thalamic ventrobasal complex","volume":"5","author":"Sikandar","year":"2017","journal-title":"Physiol. Rep."},{"key":"B48","doi-asserted-by":"publisher","first-page":"694","DOI":"10.1038\/nrneurol.2014.211","article-title":"Mechanism-based treatment for chemotherapy-induced peripheral neuropathic pain","volume":"10","author":"Sisignano","year":"2014","journal-title":"Nat. Rev. Neurol."},{"key":"B49","doi-asserted-by":"publisher","first-page":"1211","DOI":"10.3390\/ph17091211","article-title":"Therapeutic potential and mechanisms of bee venom therapy: a comprehensive review of apitoxin applications and safety enhancement strategies","volume":"17","author":"Stela","year":"2024","journal-title":"Pharmaceuticals"},{"key":"B50","doi-asserted-by":"publisher","first-page":"335","DOI":"10.2147\/NSS.S352035","article-title":"Longitudinal analysis of sleep-wake states in neonatal rats subjected to hypoxia-ischemia","volume":"14","author":"Sun","year":"2022","journal-title":"Nat. Sci. Sleep"},{"key":"B51","doi-asserted-by":"publisher","first-page":"608","DOI":"10.3390\/toxins13090608","article-title":"Bee venom acupuncture effects on pain and its mechanisms: an updated review","volume":"13","author":"Sung","year":"2021","journal-title":"Toxins"},{"key":"B52","doi-asserted-by":"publisher","first-page":"17","DOI":"10.1053\/eujp.2001.0266","article-title":"Venlafaxine in neuropathic pain following treatment of breast cancer","volume":"6","author":"Tasmuth","year":"2002","journal-title":"Eur. J. Pain"},{"key":"B53","doi-asserted-by":"publisher","first-page":"823","DOI":"10.1038\/nrn2947","article-title":"Neuronal circuitry for pain processing in the dorsal horn","volume":"11","author":"Todd","year":"2010","journal-title":"Nat. Rev. Neurosci."},{"key":"B54","doi-asserted-by":"publisher","first-page":"9257","DOI":"10.3390\/ijms22179257","article-title":"Integrated medicine for chemotherapy-induced peripheral neuropathy","volume":"22","author":"Tsai","year":"2021","journal-title":"Int. J. Mol. Sci."},{"key":"B55","doi-asserted-by":"publisher","first-page":"477","DOI":"10.3390\/toxins11080477","article-title":"Suppressive effects of bee venom-derived phospholipase A2 on mechanical allodynia in a rat model of neuropathic pain","volume":"11","author":"Woo","year":"2019","journal-title":"Toxins"},{"key":"B56","doi-asserted-by":"publisher","first-page":"1744806918817969","DOI":"10.1177\/1744806918817969","article-title":"Ethanol-induced enhancement of inhibitory synaptic transmission in the rat spinal substantia gelatinosa","volume":"14","author":"Yamada","year":"2018","journal-title":"Mol. Pain"},{"key":"B57","doi-asserted-by":"publisher","first-page":"159","DOI":"10.1016\/j.rvsc.2007.04.004","article-title":"A proposed transpositional acupoint system in a mouse and rat model","volume":"84","author":"Yin","year":"2008","journal-title":"Res. Vet. Sci."},{"key":"B58","doi-asserted-by":"publisher","first-page":"369","DOI":"10.1016\/0304-3959(94)90023-X","article-title":"Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain","volume":"59","author":"Yoon","year":"1994","journal-title":"Pain"},{"key":"B59","doi-asserted-by":"publisher","first-page":"156","DOI":"10.1016\/j.jams.2012.05.003","article-title":"Sweet bee venom pharmacopuncture for chemotherapy-induced peripheral neuropathy","volume":"5","author":"Yoon","year":"2012","journal-title":"J. Acupunct. Meridian Stud."},{"key":"B60","doi-asserted-by":"publisher","first-page":"107","DOI":"10.1254\/jphs.CRJ06008X","article-title":"Mechanisms for the anti-nociceptive actions of the descending noradrenergic and serotonergic systems in the spinal cord","volume":"101","author":"Yoshimura","year":"2006","journal-title":"J. Pharmacol. Sci."},{"key":"B61","doi-asserted-by":"publisher","first-page":"96","DOI":"10.1152\/jn.1989.62.1.96","article-title":"Primary afferent-evoked synaptic responses and slow potential generation in rat substantia gelatinosa neurons in vitro","volume":"62","author":"Yoshimura","year":"1989","journal-title":"J. Neurophysiol."},{"key":"B62","doi-asserted-by":"publisher","first-page":"108555","DOI":"10.1016\/j.intimp.2022.108555","article-title":"The interactions of paclitaxel with tumour microenvironment","volume":"105","author":"Yu","year":"2022","journal-title":"Int. Immunopharmacol."},{"key":"B63","doi-asserted-by":"publisher","first-page":"2199","DOI":"10.1097\/j.pain.0000000000001632","article-title":"Alterations in evoked and spontaneous activity of dorsal horn wide dynamic range neurons in pathological pain: a systematic review and analysis","volume":"160","author":"Zain","year":"2019","journal-title":"Pain"},{"key":"B64","doi-asserted-by":"publisher","first-page":"1451","DOI":"10.3390\/ijms20061451","article-title":"Mechanisms of Chemotherapy-Induced Peripheral Neuropathy","volume":"20","author":"Zajaczkowska","year":"2019","journal-title":"Int. J. Mol. Sci."},{"key":"B65","doi-asserted-by":"publisher","first-page":"295","DOI":"10.1007\/s10103-017-2367-7","article-title":"Laser acupuncture-induced analgesic effect and molecular alterations in an incision pain model: a comparison with electroacupuncture-induced effects","volume":"33","author":"Zeng","year":"2018","journal-title":"Lasers Med. Sci."},{"key":"B66","doi-asserted-by":"publisher","first-page":"64","DOI":"10.1016\/j.toxicon.2018.04.012","article-title":"Bee venom therapy: potential mechanisms and therapeutic applications","volume":"148","author":"Zhang","year":"2018","journal-title":"Toxicon"},{"key":"B67","doi-asserted-by":"publisher","first-page":"441","DOI":"10.2147\/JPR.S446803","article-title":"Understanding of spinal wide dynamic range neurons and their modulation on pathological pain","volume":"17","author":"Zhang","year":"2024","journal-title":"J. Pain Res."},{"key":"B68","doi-asserted-by":"publisher","first-page":"447","DOI":"10.1016\/j.neuroscience.2010.12.052","article-title":"The response of spinal microglia to chemotherapy-evoked painful peripheral neuropathies is distinct from that evoked by traumatic nerve injuries","volume":"176","author":"Zheng","year":"2011","journal-title":"Neuroscience"},{"key":"B69","first-page":"52","article-title":"Different susceptibility of lung cell lines to inhibitors of tumor promotion and inducers of differentiation","volume":"5","author":"Zhu","year":"1991","journal-title":"J. Biol. Regul. Homeost. Agents"},{"key":"B70","doi-asserted-by":"publisher","first-page":"109","DOI":"10.1016\/0304-3959(83)90201-4","article-title":"Ethical guidelines for investigations of experimental pain in conscious animals","volume":"16","author":"Zimmermann","year":"1983","journal-title":"Pain"}],"container-title":["Frontiers in Neuroscience"],"original-title":[],"link":[{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1622553\/full","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2025,7,2]],"date-time":"2025-07-02T01:52:09Z","timestamp":1751421129000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.frontiersin.org\/articles\/10.3389\/fnins.2025.1622553\/full"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2025,7,2]]},"references-count":70,"alternative-id":["10.3389\/fnins.2025.1622553"],"URL":"https:\/\/doi.org\/10.3389\/fnins.2025.1622553","relation":{},"ISSN":["1662-453X"],"issn-type":[{"value":"1662-453X","type":"electronic"}],"subject":[],"published":{"date-parts":[[2025,7,2]]},"article-number":"1622553"}}