{"status":"ok","message-type":"work","message-version":"1.0.0","message":{"indexed":{"date-parts":[[2026,9,29]],"date-time":"2026-09-29T21:14:47Z","timestamp":1790716487708,"version":"4.1.0"},"reference-count":101,"publisher":"Pharmaceutical Society of Japan","issue":"6","content-domain":{"domain":[],"crossmark-restriction":false},"short-container-title":["Biological & Pharmaceutical Bulletin","Biol. Pharm. Bull."],"published-print":{"date-parts":[[2019,6,1]]},"DOI":"10.1248\/bpb.b19-00195","type":"journal-article","created":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T18:08:34Z","timestamp":1559326114000},"page":"857-866","source":"Crossref","is-referenced-by-count":23,"title":["Role of Connexins in Chronic Pain and Their Potential as Therapeutic Targets for Next-Generation Analgesics"],"prefix":"10.1248","volume":"42","author":[{"given":"Norimitsu","family":"Morioka","sequence":"first","affiliation":[{"name":"Department of Pharmacology, Hiroshima University Graduate School of Biomedical & Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoki","family":"Nakamura","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hiroshima University Graduate School of Biomedical & Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Fang Fang","family":"Zhang","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hiroshima University Graduate School of Biomedical & Health Sciences"},{"name":"Institute of Pharmacology, Taishan Medical University"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Kazue","family":"Hisaoka-Nakashima","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hiroshima University Graduate School of Biomedical & Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]},{"given":"Yoshihiro","family":"Nakata","sequence":"additional","affiliation":[{"name":"Department of Pharmacology, Hiroshima University Graduate School of Biomedical & Health Sciences"}],"role":[{"vocabulary":"crossref","role":"author"}]}],"member":"163","reference":[{"key":"1","unstructured":"1) Millan MJ. The induction of pain: an integrative review. Prog. Neurobiol.<\/i>, 57<\/b>, 1\u2013164 (1999)."},{"key":"2","unstructured":"2) Breivik H, Collett B, Ventafridda V, Cohen R, Gallacher D. Survey of chronic pain in Europe: prevalence, impact on daily life, and treatment. Eur. J. Pain<\/i>, 10<\/b>, 287\u2013333 (2006)."},{"key":"3","doi-asserted-by":"crossref","unstructured":"3) Gereau RW 4th, Sluka KA, Maixner W, Savage SR, Price TJ, Murinson BB, Sullivan MD, Fillingim RB. A pain research agenda for the 21st century. J. Pain<\/i>, 15<\/b>, 1203\u20131214 (2014).","DOI":"10.1016\/j.jpain.2014.09.004"},{"key":"4","doi-asserted-by":"crossref","unstructured":"4) Ferreira ML, de Luca K. Spinal pain and its impact on older people. Best Pract. Res. Clin. Rheumatol.<\/i>, 31<\/b>, 192\u2013202 (2017).","DOI":"10.1016\/j.berh.2017.08.006"},{"key":"5","unstructured":"5) Gagliese L, Gauthier LR, Narain N, Freedman T. Pain, aging and dementia: towards a biopsychosocial model. Prog. Neuropsychopharmacol. Biol. Psychiatry<\/i>, 87<\/b> (Pt B), 207\u2013215 (2018)."},{"key":"6","doi-asserted-by":"crossref","unstructured":"6) Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell<\/i>, 139<\/b>, 267\u2013284 (2009).","DOI":"10.1016\/j.cell.2009.09.028"},{"key":"7","doi-asserted-by":"crossref","unstructured":"7) Ji RR, Chamessian A, Zhang YQ. Pain regulation by non-neuronal cells and inflammation. Science<\/i>, 354<\/b>, 572\u2013577 (2016).","DOI":"10.1126\/science.aaf8924"},{"key":"8","doi-asserted-by":"crossref","unstructured":"8) Grace PM, Hutchinson MR, Maier SF, Watkins LR. Pathological pain and the neuroimmune interface. Nat. Rev. Immunol.<\/i>, 14<\/b>, 217\u2013231 (2014).","DOI":"10.1038\/nri3621"},{"key":"9","doi-asserted-by":"crossref","unstructured":"9) Mika J, Zychowska M, Popiolek-Barczyk K, Rojewska E, Przewlocka B. Importance of glial activation in neuropathic pain. Eur. J. Pharmacol.<\/i>, 716<\/b>, 106\u2013119 (2013).","DOI":"10.1016\/j.ejphar.2013.01.072"},{"key":"10","doi-asserted-by":"crossref","unstructured":"10) Imai S, Ikegami D, Yamashita A, Shimizu T, Narita M, Niikura K, Furuya M, Kobayashi Y, Miyashita K, Okutsu D, Kato A, Nakamura A, Araki A, Omi K, Nakamura M, James Okano H, Okano H, Ando T, Takeshima H, Ushijima T, Kuzumaki N, Suzuki T, Narita M. Epigenetic transcriptional activation of monocyte chemotactic protein 3 contributes to long-lasting neuropathic pain. Brain<\/i>, 136<\/b>, 828\u2013843 (2013).","DOI":"10.1093\/brain\/aws330"},{"key":"11","doi-asserted-by":"crossref","unstructured":"11) Gruber-Schoffnegger D, Drdla-Schutting R, H\u00f6nigsperger C, Wunderbaldinger G, Gassner M, Sandk\u00fchler J. Induction of thermal hyperalgesia and synaptic long-term potentiation in the spinal cord lamina I by TNF-\u03b1 and IL-1\u03b2 is mediated by glial cells. J. Neurosci.<\/i>, 33<\/b>, 6540\u20136551 (2013).","DOI":"10.1523\/JNEUROSCI.5087-12.2013"},{"key":"12","doi-asserted-by":"crossref","unstructured":"12) Coull JA, Beggs S, Boudreau D, Boivin D, Tsuda M, Inoue K, Gravel C, Salter MW, De Koninck Y. BDNF from microglia causes the shift in neuronal anion gradient underlying neuropathic pain. Nature<\/i>, 438<\/b>, 1017\u20131021 (2005).","DOI":"10.1038\/nature04223"},{"key":"13","doi-asserted-by":"crossref","unstructured":"13) Kawasaki Y, Xu ZZ, Wang X, Park JY, Zhuang ZY, Tan PH, Gao YJ, Roy K, Corfas G, Lo EH, Ji RR. Distinct roles of matrix metalloproteases in the early- and late-phase development of neuropathic pain. Nat. Med.<\/i>, 14<\/b>, 331\u2013336 (2008).","DOI":"10.1038\/nm1723"},{"key":"14","doi-asserted-by":"crossref","unstructured":"14) Yeager M, Nicholson BJ. Structure of gap junction intercellular channels. Curr. Opin. Struct. Biol.<\/i>, 6<\/b>, 183\u2013192 (1996).","DOI":"10.1016\/S0959-440X(96)80073-X"},{"key":"15","doi-asserted-by":"crossref","unstructured":"15) Herrero-Gonz\u00e1lez S, Valle-Casuso JC, S\u00e1nchez-Alvarez R, Giaume C, Medina JM, Tabernero A. Connexin43 is involved in the effect of endothelin-1 on astrocyte proliferation and glucose uptake. Glia<\/i>, 57<\/b>, 222\u2013233 (2009).","DOI":"10.1002\/glia.20748"},{"key":"16","doi-asserted-by":"crossref","unstructured":"16) Langer J, Stephan J, Theis M, Rose CR. Gap junctions mediate intercellular spread of sodium between hippocampal astrocytes in situ.<\/i> Glia<\/i>, 60<\/b>, 239\u2013252 (2012).","DOI":"10.1002\/glia.21259"},{"key":"17","unstructured":"17) S\u00e1ez JC, Berthoud VM, Bra\u00f1es MC, Mart\u00ednez AD, Beyer EC. Plasma membrane channels formed by connexins: their regulation and functions. Physiol. Rev.<\/i>, 83<\/b>, 1359\u20131400 (2003)."},{"key":"18","unstructured":"18) Orellana JA, Martinez AD, Retamal MA. Gap junction channels and hemichannels in the CNS: regulation by signaling molecules. Neuropharmacology<\/i>, 75<\/b>, 567\u2013582 (2013)."},{"key":"19","doi-asserted-by":"crossref","unstructured":"19) Mroue RM, El-Sabban ME, Talhouk RS. Connexins and the gap in context. Integr. Biol.<\/i>, 3<\/b>, 255\u2013266 (2011).","DOI":"10.1039\/c0ib00158a"},{"key":"20","doi-asserted-by":"crossref","unstructured":"20) Kumar NM, Gilula NB. The gap junction communication channel. Cell<\/i>, 84<\/b>, 381\u2013388 (1996).","DOI":"10.1016\/S0092-8674(00)81282-9"},{"key":"21","doi-asserted-by":"crossref","unstructured":"21) Reyes EP, Cerpa V, Corval\u00e1n L, Retamal MA. Cxs and Panx- hemichannels in peripheral and central chemosensing in mammals. Front. Cell. Neurosci.<\/i>, 8<\/b>, 123 (2014).","DOI":"10.3389\/fncel.2014.00123"},{"key":"22","unstructured":"22) Bennett MV, Contreras JE, Bukauskas FF, S\u00e1ez JC. New roles for astrocytes: gap junction hemichannels have something to communicate. Trends Neurosci.<\/i>, 26<\/b>, 610\u2013617 (2003)."},{"key":"23","doi-asserted-by":"crossref","unstructured":"23) S\u00f6hl G, Willecke K. An update on connexin genes and their nomenclature in mouse and man. Cell Commun. Adhes.<\/i>, 10<\/b>, 173\u2013180 (2003).","DOI":"10.1080\/714040423"},{"key":"24","doi-asserted-by":"crossref","unstructured":"24) Wu A, Green CR, Rupenthal ID, Moalem-Taylor G. Role of gap junctions in chronic pain. J. Neurosci. Res.<\/i>, 90<\/b>, 337\u2013345 (2012).","DOI":"10.1002\/jnr.22764"},{"key":"25","doi-asserted-by":"crossref","unstructured":"25) Nualart-Marti A, Solsona C, Fields RD. Gap junction communication in myelinating glia. Biochim. Biophys. Acta<\/i>, 1828<\/b>, 69\u201378 (2013).","DOI":"10.1016\/j.bbamem.2012.01.024"},{"key":"26","doi-asserted-by":"crossref","unstructured":"26) S\u00f6hl G, Maxeiner S, Willecke K. Expression and functions of neuronal gap junctions. Nat. Rev. Neurosci.<\/i>, 6<\/b>, 191\u2013200 (2005).","DOI":"10.1038\/nrn1627"},{"key":"27","unstructured":"27) Giaume C, Koulakoff A, Roux L, Holcman D, Rouach N. Astroglial networks: a step further in neuroglial and gliovascular interactions. Nat. Rev. Neurosci.<\/i>, 11<\/b>, 87\u201399 (2010)."},{"key":"28","unstructured":"28) Giaume C, Fromaget C, el Aoumari A, Cordier J, Glowinski J, Grost D. Gap junctions in cultured astrocytes: single-channel currents and characterization of channel-forming protein. Neuron<\/i>, 6<\/b>, 133\u2013143 (1991)."},{"key":"29","unstructured":"29) Nagy JI, Li X, Rempel J, Stelmack G, Patel D, Staines WA, Yasumura T, Rash JE. Connexin26 in adult rodent central nervous system: demonstration at astrocytic gap junctions and colocalization with connexin30 and connexin43. J. Comp. Neurol.<\/i>, 441<\/b>, 302\u2013323 (2001)."},{"key":"30","doi-asserted-by":"crossref","unstructured":"30) Eugen\u00edn EA, Eckardt D, Theis M, Willecke K, Bennett MV, Saez JC. Microglia at brain stab wounds express connexin 43 and in vitro<\/i> form functional gap junctions after treatment with interferon-\u03b3 and tumor necrosis factor-\u03b1. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 98<\/b>, 4190\u20134195 (2001).","DOI":"10.1073\/pnas.051634298"},{"key":"31","doi-asserted-by":"crossref","unstructured":"31) Kaji K, Shinoda M, Honda K, Unno S, Shimizu N, Iwata K. Connexin 43 contributes to ectopic orofacial pain following inferior alveolar nerve injury. Mol. Pain<\/i>, 12<\/b> (2016).","DOI":"10.1177\/1744806916633704"},{"key":"32","doi-asserted-by":"crossref","unstructured":"32) Ohara PT, Vit JP, Bhargava A, Jasmin L. Evidence for a role of connexin 43 in trigeminal pain using RNA interference in vivo.<\/i> J. Neurophysiol.<\/i>, 100<\/b>, 3064\u20133073 (2008).","DOI":"10.1152\/jn.90722.2008"},{"key":"33","doi-asserted-by":"crossref","unstructured":"33) P\u00e9rez Armendariz EM, Norcini M, Hern\u00e1ndez-Tellez B, Castell-Rodr\u00edguez A, Coronel-Cruz C, Alquicira RG, Sideris A, Recio-Pinto E. Neurons and satellite glial cells in adult rat lumbar dorsal root ganglia express connexin 36. Acta Histochem.<\/i>, 120<\/b>, 168\u2013178 (2018).","DOI":"10.1016\/j.acthis.2017.11.005"},{"key":"34","doi-asserted-by":"crossref","unstructured":"34) Neumann E, Hermanns H, Barthel F, Werdehausen R, Brandenburger T. 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<\/i>, 11<\/b>, 39 (2015).","DOI":"10.1186\/s12990-015-0045-y"},{"key":"35","doi-asserted-by":"crossref","unstructured":"35) Morioka N, Zhang FF, Nakamura Y, Kitamura T, Hisaoka-Nakashima K, Nakata Y. Tumor necrosis factor-mediated downregulation of spinal astrocytic connexin43 leads to increased glutamatergic neurotransmission and neuropathic pain in mice. Brain Behav. Immun.<\/i>, 49<\/b>, 293\u2013310 (2015).","DOI":"10.1016\/j.bbi.2015.06.015"},{"key":"36","doi-asserted-by":"crossref","unstructured":"36) Chen MJ, Kress B, Han X, Moll K, Peng W, Ji RR, Nedergaard M. Astrocytic CX43 hemichannels and gap junctions play a crucial role in development of chronic neuropathic pain following spinal cord injury. Glia<\/i>, 60<\/b>, 1660\u20131670 (2012).","DOI":"10.1002\/glia.22384"},{"key":"37","doi-asserted-by":"crossref","unstructured":"37) Tonkin RS, Bowles C, Perera CJ, Keating BA, Makker PGS, Duffy SS, Lees JG, Tran C, Don AS, Fath T, Liu L, O\u2019Carroll SJ, Nicholson LFB, Green CR, Gorrie C, Moalem-Taylor G. Attenuation of mechanical pain hypersensitivity by treatment with Peptide5, a connexin-43 mimetic peptide, involves inhibition of NLRP3 inflammasome in nerve-injured mice. Exp. Neurol.<\/i>, 300<\/b>, 1\u201312 (2018).","DOI":"10.1016\/j.expneurol.2017.10.016"},{"key":"38","doi-asserted-by":"crossref","unstructured":"38) Wang H, Sun X. Carbon monoxide-releasing molecule-2 inhibits connexin 43-hemichannel activity in spinal cord astrocytes to attenuate neuropathic pain. J. Mol. Neurosci.<\/i>, 63<\/b>, 58\u201369 (2017).","DOI":"10.1007\/s12031-017-0957-2"},{"key":"39","doi-asserted-by":"crossref","unstructured":"39) Choi SR, Roh DH, Yoon SY, Kwon SG, Choi HS, Han HJ, Beitz AJ, Lee JH. Astrocyte sigma-1 receptors modulate connexin 43 expression leading to the induction of below-level mechanical allodynia in spinal cord injured mice. Neuropharmacology<\/i>, 111<\/b>, 34\u201346 (2016).","DOI":"10.1016\/j.neuropharm.2016.08.027"},{"key":"40","doi-asserted-by":"crossref","unstructured":"40) Choi HS, Roh DH, Yoon SY, Kwon SG, Choi SR, Kang SY, Moon JY, Han HJ, Kim HW, Beitz AJ, Lee JH. The role of spinal interleukin-1\u03b2 and astrocyte connexin 43 in the development of mirror-image pain in an inflammatory pain model. Exp. Neurol.<\/i>, 287<\/b>, 1\u201313 (2017).","DOI":"10.1016\/j.expneurol.2016.10.012"},{"key":"41","doi-asserted-by":"crossref","unstructured":"41) Robinson CR, Dougherty PM. Spinal astrocyte gap junction and glutamate transporter expression contributes to a rat model of bortezomib-induced peripheral neuropathy. Neuroscience<\/i>, 285<\/b>, 1\u201310 (2015).","DOI":"10.1016\/j.neuroscience.2014.11.009"},{"key":"42","doi-asserted-by":"crossref","unstructured":"42) Yoon SY, Robinson CR, Zhang H, Dougherty PM. Spinal astrocyte gap junctions contribute to oxaliplatin-induced mechanical hypersensitivity. J. Pain<\/i>, 14<\/b>, 205\u2013214 (2013).","DOI":"10.1016\/j.jpain.2012.11.002"},{"key":"43","doi-asserted-by":"crossref","unstructured":"43) Yang H, Yan H, Li X, Liu J, Cao S, Huang B, Huang D, Wu L. Inhibition of connexin 43 and phosphorylated NR2B in spinal astrocytes attenuates bone cancer pain in mice. Front. Cell. Neurosci.<\/i>, 12<\/b>, 129 (2018).","DOI":"10.3389\/fncel.2018.00129"},{"key":"44","doi-asserted-by":"crossref","unstructured":"44) Chen G, Park CK, Xie RG, Berta T, Nedergaard M, Ji RR. Connexin-43 induces chemokine release from spinal cord astrocytes to maintain late-phase neuropathic pain in mice. Brain<\/i>, 137<\/b>, 2193\u20132209 (2014).","DOI":"10.1093\/brain\/awu140"},{"key":"45","doi-asserted-by":"crossref","unstructured":"45) Klotz LO. Posttranscriptional regulation of connexin-43 expression. Arch. Biochem. Biophys.<\/i>, 524<\/b>, 23\u201329 (2012).","DOI":"10.1016\/j.abb.2012.03.012"},{"key":"46","unstructured":"46) L\u00f3pez-Gonz\u00e1lez MJ, Landry M, Favereaux A. MicroRNA and chronic pain: From mechanisms to therapeutic potential. Pharmacol. Ther.<\/i>, 180<\/b>, 1\u201315 (2017)."},{"key":"47","doi-asserted-by":"crossref","unstructured":"47) Lu Y, Cao DL, Jiang BC, Yang T, Gao YJ. MicroRNA-146a-5p attenuates neuropathic pain via<\/i> suppressing TRAF6 signaling in the spinal cord. Brain Behav. Immun.<\/i>, 49<\/b>, 119\u2013129 (2015).","DOI":"10.1016\/j.bbi.2015.04.018"},{"key":"48","unstructured":"48) Silva RL, Lopes AH, Guimar\u00e3es RM, Cunha TM. CXCL1\/CXCR2 signaling in pathological pain: Role in peripheral and central sensitization. Neurobiol. Dis.<\/i>, 105<\/b>, 109\u2013116 (2017)."},{"key":"49","unstructured":"49) Shen N, Mo LQ, Hu F, Chen PX, Guo RX, Feng JQ. A novel role of spinal astrocytic connexin 43: mediating morphine antinociceptive tolerance by activation of NMDA receptors and inhibition of glutamate transporter-1 in rats. CNS Neurosci. Ther.<\/i>, 20<\/b>, 728\u2013736 (2014)."},{"key":"50","doi-asserted-by":"crossref","unstructured":"50) Grace PM, Strand KA, Galer EL, Urban DJ, Wang X, Baratta MV, Fabisiak TJ, Anderson ND, Cheng K, Greene LI, Berkelhammer D, Zhang Y, Ellis AL, Yin HH, Campeau S, Rice KC, Roth BL, Maier SF, Watkins LR. Morphine paradoxically prolongs neuropathic pain in rats by amplifying spinal NLRP3 inflammasome activation. Proc. Natl. Acad. Sci. U.S.A.<\/i>, 113<\/b>, E3441\u2013E3450 (2016).","DOI":"10.1073\/pnas.1602070113"},{"key":"51","doi-asserted-by":"crossref","unstructured":"51) Xu Q, Cheong YK, He SQ, Tiwari V, Liu J, Wang Y, Raja SN, Li J, Guan Y, Li W. Suppression of spinal connexin 43 expression attenuates mechanical hypersensitivity in rats after an L5 spinal nerve injury. Neurosci. Lett.<\/i>, 566<\/b>, 194\u2013199 (2014).","DOI":"10.1016\/j.neulet.2014.03.004"},{"key":"52","doi-asserted-by":"crossref","unstructured":"52) Inoue K. The function of microglia through purinergic receptors: neuropathic pain and cytokine release. Pharmacol. Ther.<\/i>, 109<\/b>, 210\u2013226 (2006).","DOI":"10.1016\/j.pharmthera.2005.07.001"},{"key":"53","doi-asserted-by":"crossref","unstructured":"53) Zhang FF, Morioka N, Nakashima-Hisaoka K, Nakata Y. Spinal astrocytes stimulated by tumor necrosis factor-\u03b1 and\/or interferon-\u03b3 attenuate connexin 43-gap junction via<\/i> c-jun terminal kinase activity. J. Neurosci. Res.<\/i>, 91<\/b>, 745\u2013756 (2013).","DOI":"10.1002\/jnr.23213"},{"key":"54","doi-asserted-by":"crossref","unstructured":"54) Zhang FF, Morioka N, Kitamura T, Hisaoka-Nakashima K, Nakata Y. Proinflammatory cytokines downregulate connexin 43-gap junctions via<\/i> the ubiquitin\u2013proteasome system in rat spinal astrocytes. Biochem. Biophys. Res. Commun.<\/i>, 464<\/b>, 1202\u20131208 (2015).","DOI":"10.1016\/j.bbrc.2015.07.105"},{"key":"55","unstructured":"55) M\u00eame W, Calvo CF, Froger N, Ezan P, Amigou E, Koulakoff A, Giaume C. Proinflammatory cytokines released from microglia inhibit gap junctions in astrocytes: potentiation by beta-amyloid. FASEB J.<\/i>, 20<\/b>, 494\u2013496 (2006)."},{"key":"56","doi-asserted-by":"crossref","unstructured":"56) Retamal MA, Froger N, Palacios-Prado N, Ezan P, S\u00e1ez PJ, S\u00e1ez JC, Giaume C. Cx43 hemichannels and gap junction channels in astrocytes are regulated oppositely by proinflammatory cytokines released from activated microglia. J. Neurosci.<\/i>, 27<\/b>, 13781\u201313792 (2007).","DOI":"10.1523\/JNEUROSCI.2042-07.2007"},{"key":"57","doi-asserted-by":"crossref","unstructured":"57) Liao CK, Wang SM, Chen YL, Wang HS, Wu JC. Lipopolysaccharide-induced inhibition of connexin43 gap junction communication in astrocytes is mediated by downregulation of caveolin-3. Int. J. Biochem. Cell Biol.<\/i>, 42<\/b>, 762\u2013770 (2010).","DOI":"10.1016\/j.biocel.2010.01.016"},{"key":"58","doi-asserted-by":"crossref","unstructured":"58) Liao CK, Jeng CJ, Wang HS, Wang SH, Wu JC. Lipopolysaccharide induces degradation of connexin43 in rat astrocytes via<\/i> the ubiquitin-proteasome proteolytic pathway. PLOS ONE<\/i>, 8<\/b>, e79350 (2013).","DOI":"10.1371\/journal.pone.0079350"},{"key":"59","doi-asserted-by":"crossref","unstructured":"59) Solan JL, Lampe PD. Connexin phosphorylation as a regulatory event linked to gap junction channel assembly. Biochim. Biophys. Acta<\/i>, 1711<\/b>, 154\u2013163 (2005).","DOI":"10.1016\/j.bbamem.2004.09.013"},{"key":"60","doi-asserted-by":"crossref","unstructured":"60) Wu XF, Liu WT, Liu YP, Huang ZJ, Zhang YK, Song XJ. Reopening of ATP-sensitive potassium channels reduces neuropathic pain and regulates astroglial gap junctions in the rat spinal cord. Pain<\/i>, 152<\/b>, 2605\u20132615 (2011).","DOI":"10.1016\/j.pain.2011.08.003"},{"key":"61","doi-asserted-by":"crossref","unstructured":"61) Hang LH, Li SN, Luo H, Shu WW, Mao ZM, Chen YF, Shi LL, Shao DH. Connexin 43 mediates CXCL12 production from spinal dorsal horn to maintain bone cancer pain in rats. Neurochem. Res.<\/i>, 41<\/b>, 1200\u20131208 (2016).","DOI":"10.1007\/s11064-015-1815-7"},{"key":"62","doi-asserted-by":"crossref","unstructured":"62) Solan JL, Lampe PD. Key connexin 43 phosphorylation events regulate the gap junction life cycle. J. Membr. Biol.<\/i>, 217<\/b>, 35\u201341 (2007).","DOI":"10.1007\/s00232-007-9035-y"},{"key":"63","doi-asserted-by":"crossref","unstructured":"63) Morioka N, Fujii S, Kondo S, Zhang FF, Miyauchi K, Nakamura Y, Hisaoka-Nakashima K, Nakata Y. Downregulation of spinal astrocytic connexin43 leads to upregulation of interleukin-6 and cyclooxygenase-2 and mechanical hypersensitivity in mice. Glia<\/i>, 66<\/b>, 428\u2013444 (2018).","DOI":"10.1002\/glia.23255"},{"key":"64","doi-asserted-by":"crossref","unstructured":"64) Zhou JZ, Jiang JX. Gap junction and hemichannel-independent actions of connexins on cell and tissue functions\u2014an update. FEBS Lett.<\/i>, 588<\/b>, 1186\u20131192 (2014).","DOI":"10.1016\/j.febslet.2014.01.001"},{"key":"65","doi-asserted-by":"crossref","unstructured":"65) Scemes E. Modulation of astrocyte P2Y1 receptors by the carboxyl terminal domain of the gap junction protein Cx43. Glia<\/i>, 56<\/b>, 145\u2013153 (2008).","DOI":"10.1002\/glia.20598"},{"key":"66","unstructured":"66) Leithe E, Mesnil M, Aasen T. The connexin 43 C-terminus: a tail of many tales. Biochim Biophys Acta Biomembr<\/i>, 1860<\/b>, 48\u201364 (2018)."},{"key":"67","doi-asserted-by":"crossref","unstructured":"67) Herv\u00e9 JC, Derangeon M, Sarrouilhe D, Giepmans BN, Bourmeyster N. Gap junctional channels are parts of multiprotein complexes. Biochim. Biophys. Acta<\/i>, 1818<\/b>, 1844\u20131865 (2012).","DOI":"10.1016\/j.bbamem.2011.12.009"},{"key":"68","doi-asserted-by":"crossref","unstructured":"68) Iacobas DA, Scemes E, Spray DC. Gene expression alterations in connexin null mice extend beyond the gap junction. Neurochem. Int.<\/i>, 45<\/b>, 243\u2013250 (2004).","DOI":"10.1016\/j.neuint.2003.12.008"},{"key":"69","doi-asserted-by":"crossref","unstructured":"69) Filippov MA, Hormuzdi SG, Fuchs EC, Monyer H. A reporter allele for investigating connexin 26 gene expression in the mouse brain. Eur. J. Neurosci.<\/i>, 18<\/b>, 3183\u20133192 (2003).","DOI":"10.1111\/j.1460-9568.2003.03042.x"},{"key":"70","unstructured":"70) Belousov AB, Fontes JD. Neuronal gap junctions: making and breaking connections during development and injury. Trends Neurosci.<\/i>, 36<\/b>, 227\u2013236 (2013)."},{"key":"71","doi-asserted-by":"crossref","unstructured":"71) Parenti R, Gulisano M, Zappal\u00e1 A, Cicirata F. Expression of connexin36 mRNA in adult rodent brain. Neuroreport<\/i>, 11<\/b>, 1497\u20131502 (2000).","DOI":"10.1097\/00001756-200005150-00028"},{"key":"72","doi-asserted-by":"crossref","unstructured":"72) Vervaeke K, Lorincz A, Gleeson P, Farinella M, Nusser Z, Silver RA. Rapid desynchronization of an electrically coupled interneuron network with sparse excitatory synaptic input. Neuron<\/i>, 67<\/b>, 435\u2013451 (2010).","DOI":"10.1016\/j.neuron.2010.06.028"},{"key":"73","doi-asserted-by":"crossref","unstructured":"73) Beheshti S, Sayyah M, Golkar M, Sepehri H, Babaie J, Vaziri B. Changes in hippocampal connexin 36 mRNA and protein levels during epileptogenesis in the kindling model of epilepsy. Prog. Neuropsychopharmacol. Biol. Psychiatry<\/i>, 34<\/b>, 510\u2013515 (2010).","DOI":"10.1016\/j.pnpbp.2010.02.006"},{"key":"74","doi-asserted-by":"crossref","unstructured":"74) Wang Y, Song JH, Denisova JV, Park WM, Fontes JD, Belousov AB. Neuronal gap junction coupling is regulated by glutamate and plays critical role in cell death during neuronal injury. J. Neurosci.<\/i>, 32<\/b>, 713\u2013725 (2012).","DOI":"10.1523\/JNEUROSCI.3872-11.2012"},{"key":"75","doi-asserted-by":"crossref","unstructured":"75) Belousov AB, Wang Y, Song JH, Denisova JV, Berman NE, Fontes JD. Neuronal gap junctions play a role in the secondary neuronal death following controlled cortical impact. Neurosci. Lett.<\/i>, 524<\/b>, 16\u201319 (2012).","DOI":"10.1016\/j.neulet.2012.06.065"},{"key":"76","doi-asserted-by":"crossref","unstructured":"76) Nakamura Y, Morioka N, Zhang FF, Hisaoka-Nakashima K, Nakata Y. Downregulation of connexin36 in mouse spinal dorsal horn neurons leads to mechanical allodynia. J. Neurosci. Res.<\/i>, 93<\/b>, 584\u2013591 (2015).","DOI":"10.1002\/jnr.23515"},{"key":"77","doi-asserted-by":"crossref","unstructured":"77) Masocha W. Astrocyte activation in the anterior cingulate cortex and altered glutamatergic gene expression during paclitaxel-induced neuropathic pain in mice. PeerJ<\/i>, 3<\/b>, e1350 (2015).","DOI":"10.7717\/peerj.1350"},{"key":"78","doi-asserted-by":"crossref","unstructured":"78) Tsuda M, Koga K, Chen T, Zhuo M. Neuronal and microglial mechanisms for neuropathic pain in the spinal dorsal horn and anterior cingulate cortex. J. Neurochem.<\/i>, 141<\/b>, 486\u2013498 (2017).","DOI":"10.1111\/jnc.14001"},{"key":"79","doi-asserted-by":"crossref","unstructured":"79) Chen ZY, Shen FY, Jiang L, Zhao X, Shen XL, Zhong W, Liu S, Wang ZR, Wang YW. Attenuation of neuropathic pain by inhibiting electrical synapses in the anterior cingulate cortex. Anesthesiology<\/i>, 124<\/b>, 169\u2013183 (2016).","DOI":"10.1097\/ALN.0000000000000942"},{"key":"80","unstructured":"80) Takeuchi H, Suzumura A. Gap junctions and hemichannels composed of connexins: potential therapeutic targets for neurodegenerative diseases. Front. Cell. Neurosci.<\/i>, 8<\/b>, 189 (2014)."},{"key":"81","doi-asserted-by":"crossref","unstructured":"81) Zarpelon AC, Rodrigues FC, Lopes AH, Souza GR, Carvalho TT, Pinto LG, Xu D, Ferreira SH, Alves-Filho JC, McInnes IB, Ryffel B, Quesniaux VF, Reverchon F, Mortaud S, Menuet A, Liew FY, Cunha FQ, Cunha TM, Verri WA Jr. Spinal cord oligodendrocyte-derived alarmin IL-33 mediates neuropathic pain. FASEB J.<\/i>, 30<\/b>, 54\u201365 (2016).","DOI":"10.1096\/fj.14-267146"},{"key":"82","doi-asserted-by":"crossref","unstructured":"82) Qin M, Wang JJ, Cao R, Zhang H, Duan L, Gao B, Xiong YF, Chen LW, Rao ZR. The lumbar spinal cord glial cells actively modulate subcutaneous formalin induced hyperalgesia in the rat. Neurosci. Res.<\/i>, 55<\/b>, 442\u2013450 (2006).","DOI":"10.1016\/j.neures.2006.04.017"},{"key":"83","doi-asserted-by":"crossref","unstructured":"83) Cina C, Bechberger JF, Ozog MA, Naus CC. Expression of connexins in embryonic mouse neocortical development. J. Comp. Neurol.<\/i>, 504<\/b>, 298\u2013313 (2007).","DOI":"10.1002\/cne.21426"},{"key":"84","doi-asserted-by":"crossref","unstructured":"84) Chang Q, Gonzalez M, Pinter MJ, Balice-Gordon RJ. Gap junctional coupling and patterns of connexin expression among neonatal rat lumbar spinal motor neurons. J. Neurosci.<\/i>, 19<\/b>, 10813\u201310828 (1999).","DOI":"10.1523\/JNEUROSCI.19-24-10813.1999"},{"key":"85","doi-asserted-by":"crossref","unstructured":"85) Lin SH, Lu CY, Muhammad R, Chou WY, Lin FC, Wu PC, Lin CR, Yang LC. Induction of connexin 37 expression in a rat model of neuropathic pain. Brain Res. Mol. Brain Res.<\/i>, 99<\/b>, 134\u2013140 (2002).","DOI":"10.1016\/S0169-328X(02)00112-2"},{"key":"86","doi-asserted-by":"crossref","unstructured":"86) Maxeiner S, Kr\u00fcger O, Schilling K, Traub O, Urschel S, Willecke K. Spatiotemporal transcription of connexin45 during brain development results in neuronal expression in adult mice. Neuroscience<\/i>, 119<\/b>, 689\u2013700 (2003).","DOI":"10.1016\/S0306-4522(03)00077-0"},{"key":"87","unstructured":"87) Chapman RJ, Lall VK, Maxeiner S, Willecke K, Deuchars J, King AE. Localization of neurones expressing the gap junction protein Connexin45 within the adult spinal dorsal horn: a study using Cx45-eGFP reporter mice. Brain Struct. Funct.<\/i>, 218<\/b>, 751\u2013765 (2013)."},{"key":"88","doi-asserted-by":"crossref","unstructured":"88) Zhang FF, Morioka N, Kitamura T, Fujii S, Miyauchi K, Nakamura Y, Hisaoka-Nakashima K, Nakata Y. Lycopene ameliorates neuropathic pain by upregulating spinal astrocytic connexin 43 expression. Life Sci.<\/i>, 155<\/b>, 116\u2013122 (2016).","DOI":"10.1016\/j.lfs.2016.05.021"},{"key":"89","doi-asserted-by":"crossref","unstructured":"89) Fornelli F, Leone A, Verdesca I, Minervini F, Zacheo G. The influence of lycopene on the proliferation of human breast cell line (MCF-7). Toxicol. In Vitro<\/i>, 21<\/b>, 217\u2013223 (2007).","DOI":"10.1016\/j.tiv.2006.09.024"},{"key":"90","doi-asserted-by":"crossref","unstructured":"90) Chalabi N, Delort L, Satih S, D\u00e9chelotte P, Bignon YJ, Bernard-Gallon DJ. Immunohistochemical expression of RARalpha, RARbeta, and Cx43 in breast tumor cell lines after treatment with lycopene and correlation with RT-QPCR. J. Histochem. Cytochem.<\/i>, 55<\/b>, 877\u2013883 (2007).","DOI":"10.1369\/jhc.7A7185.2007"},{"key":"91","unstructured":"91) Kremer M, Salvat E, Muller A, Yalcin I, Barrot M. Antidepressants and gabapentinoids in neuropathic pain: mechanistic insights. Neuroscience<\/i>, 338<\/b>, 183\u2013206 (2016)."},{"key":"92","doi-asserted-by":"crossref","unstructured":"92) Morioka N, Suekama K, Zhang FF, Kajitani N, Hisaoka-Nakashima K, Takebayashi M, Nakata Y. Amitriptyline up-regulates connexin43-gap junction in rat cultured cortical astrocytes via<\/i> activation of the p38 and c-Fos\/AP-1 signalling pathway. Br. J. Pharmacol.<\/i>, 171<\/b>, 2854\u20132867 (2014).","DOI":"10.1111\/bph.12614"},{"key":"93","doi-asserted-by":"crossref","unstructured":"93) Sun JD, Liu Y, Yuan YH, Li J, Chen NH. Gap junction dysfunction in the prefrontal cortex induces depressive-like behaviors in rats. Neuropsychopharmacology<\/i>, 37<\/b>, 1305\u20131320 (2012).","DOI":"10.1038\/npp.2011.319"},{"key":"94","doi-asserted-by":"crossref","unstructured":"94) Al-Ubaidi MR, White TW, Ripps H, Poras I, Avner P, Gom\u00e8s D, Bruzzone R. Functional properties, developmental regulation, and chromosomal localization of murine connexin36, a gap-junctional protein expressed preferentially in retina and brain. J. Neurosci. Res.<\/i>, 59<\/b>, 813\u2013826 (2000).","DOI":"10.1002\/(SICI)1097-4547(20000315)59:6<813::AID-JNR14>3.0.CO;2-#"},{"key":"95","doi-asserted-by":"crossref","unstructured":"95) Delmar M, Makita N. Cardiac connexins, mutations and arrhythmias. Curr. Opin. Cardiol.<\/i>, 27<\/b>, 236\u2013241 (2012).","DOI":"10.1097\/HCO.0b013e328352220e"},{"key":"96","doi-asserted-by":"crossref","unstructured":"96) Yoshino A, Okamoto Y, Doi M, Otsuru N, Okada G, Takamura M, Ichikawa N, Yokoyama S, Yamashita H, Yamawaki S. Regional brain functions in the resting state indicative of potential differences between depression and chronic pain. Sci. Rep.<\/i>, 7<\/b>, 3003 (2017).","DOI":"10.1038\/s41598-017-03522-1"},{"key":"97","doi-asserted-by":"crossref","unstructured":"97) Nagasaka K, Yamanaka K, Ogawa S, Takamatsu H, Higo N. Brain activity changes in a macaque model of oxaliplatin-induced neuropathic cold hypersensitivity. Sci. Rep.<\/i>, 7<\/b>, 4305 (2017).","DOI":"10.1038\/s41598-017-04677-7"},{"key":"98","doi-asserted-by":"crossref","unstructured":"98) Fiore NT, Austin PJ. Are the emergence of affective disturbances in neuropathic pain states contingent on supraspinal neuroinflammation? Brain Behav. Immun.<\/i>, 56<\/b>, 397\u2013411 (2016).","DOI":"10.1016\/j.bbi.2016.04.012"},{"key":"99","unstructured":"99) Torta R, Ieraci V, Zizzi F. A review of the emotional aspects of neuropathic pain: from comorbidity to co-pathogenesis. Pain Ther<\/i>, 6<\/b> (Suppl. 1), 11\u201317 (2017)."},{"key":"100","doi-asserted-by":"crossref","unstructured":"100) Bernard R, Kerman IA, Thompson RC, Jones EG, Bunney WE, Barchas JD, Schatzberg AF, Myers RM, Akil H, Watson SJ. Altered expression of glutamate signaling, growth factor, and glia genes in the locus coeruleus of patients with major depression. Mol. Psychiatry<\/i>, 16<\/b>, 634\u2013646 (2011).","DOI":"10.1038\/mp.2010.44"},{"key":"101","unstructured":"101) Hama A, Natsume T, Ogawa S, Higo N, Hayashi I, Takamatsu H. Gaps in understanding mechanism and lack of treatments: potential use of a nonhuman primate model of oxaliplatin-induced neuropathic pain. Pain Res. Manag.<\/i>, 2018<\/b>, 1630709 (2018)."}],"container-title":["Biological and Pharmaceutical Bulletin"],"original-title":[],"language":"en","link":[{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/42\/6\/42_b19-00195\/_pdf","content-type":"unspecified","content-version":"vor","intended-application":"similarity-checking"}],"deposited":{"date-parts":[[2019,5,31]],"date-time":"2019-05-31T23:28:46Z","timestamp":1559345326000},"score":1,"resource":{"primary":{"URL":"https:\/\/www.jstage.jst.go.jp\/article\/bpb\/42\/6\/42_b19-00195\/_article"}},"subtitle":[],"short-title":[],"issued":{"date-parts":[[2019,6,1]]},"references-count":101,"journal-issue":{"issue":"6","published-print":{"date-parts":[[2019]]}},"URL":"https:\/\/doi.org\/10.1248\/bpb.b19-00195","relation":{},"ISSN":["0918-6158","1347-5215"],"issn-type":[{"value":"0918-6158","type":"print"},{"value":"1347-5215","type":"electronic"}],"subject":[],"published":{"date-parts":[[2019,6,1]]}}}