Advertisement

Involvement of TACAN, a Mechanotransducing Ion Channel, in Inflammatory But Not Neuropathic Hyperalgesia in the Rat

  • Ivan J.M. Bonet
    Affiliations
    Departments of Medicine and Oral & Maxillofacial Surgery, and Division of Neuroscience, UCSF Pain and Addiction Research Center, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, California
    Search for articles by this author
  • Dionéia Araldi
    Affiliations
    Departments of Medicine and Oral & Maxillofacial Surgery, and Division of Neuroscience, UCSF Pain and Addiction Research Center, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, California
    Search for articles by this author
  • Oliver Bogen
    Affiliations
    Departments of Medicine and Oral & Maxillofacial Surgery, and Division of Neuroscience, UCSF Pain and Addiction Research Center, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, California
    Search for articles by this author
  • Jon D. Levine
    Correspondence
    Address reprint requests to Jon D. Levine, MD, PhD, University of California, San Francisco, 513 Parnassus Avenue, San Francisco, CA 94143-0440.
    Affiliations
    Departments of Medicine and Oral & Maxillofacial Surgery, and Division of Neuroscience, UCSF Pain and Addiction Research Center, University of California at San Francisco, 513 Parnassus Avenue, San Francisco, California
    Search for articles by this author
Published:November 20, 2020DOI:https://doi.org/10.1016/j.jpain.2020.11.004

      Highlights

      • Knocking down TACAN in DRG cells increases mechanical nociceptive threshold.
      • TACAN plays a crucial role in inflammatory mechanical hyperalgesia.
      • Chemotherapy-induced peripheral neuropathy is not dependent on TACAN.

      Abstract

      TACAN (Tmem120A), a mechanotransducing ion channel highly expressed in a subset of nociceptors, has recently been shown to contribute to detection of noxious mechanical stimulation. In the present study we evaluated its role in sensitization to mechanical stimuli associated with preclinical models of inflammatory and chemotherapy-induced neuropathic pain (CIPN). Intrathecal administration of an oligodeoxynucleotide antisense (AS-ODN) to TACAN mRNA attenuated TACAN protein expression in rat dorsal root ganglia (DRG). While TACAN AS-ODN produced only a modest increase in mechanical nociceptive threshold, it markedly reduced mechanical hyperalgesia produced by intradermal administration of prostaglandin E2, tumor necrosis factor alpha, and low molecular weight hyaluronan, and systemic administration of lipopolysaccharide, compatible with a prominent role of TACAN in mechanical hyperalgesia produced by inflammation. In contrast, TACAN AS-ODN had no effect on mechanical hyperalgesia associated with CIPN produced by oxaliplatin or paclitaxel. Our results provide evidence that TACAN plays a role in mechanical hyperalgesia induced by pronociceptive inflammatory mediators, but not CIPN, compatible with multiple mechanisms mediating mechanical nociception, and sensitization to mechanical stimuli in preclinical models of inflammatory versus CIPN.

      Perspective

      We evaluated the role of TACAN, a mechanotransducing ion channel in nociceptors, in preclinical models of inflammatory and CIPN. Attenuation of TACAN expression reduced hyperalgesia produced by inflammatory mediators but had not chemotherapeutic agents. Our findings support the presence of multiple mechanotransducers in nociceptors.

      Keywords

      To read this article in full you will need to make a payment

      Purchase one-time access:

      Academic & Personal: 24 hour online accessCorporate R&D Professionals: 24 hour online access
      One-time access price info
      • For academic or personal research use, select 'Academic and Personal'
      • For corporate R&D use, select 'Corporate R&D Professionals'

      Subscribe:

      Subscribe to The Journal of Pain
      Already a print subscriber? Claim online access
      Already an online subscriber? Sign in
      Institutional Access: Sign in to ScienceDirect

      References

        • Adams J.D.
        • Flora K.P.
        • Goldspiel B.R.
        • Wilson J.W.
        • Arbuck S.G.
        • Finley R.
        Taxol: a history of pharmaceutical development and current pharmaceutical concerns.
        J Natl Cancer Inst Monogr. 1993; 15: 141-147
        • Alessandri-Haber N.
        • Yeh J.J.
        • Boyd A.E.
        • Parada C.A.
        • Chen X.
        • Reichling D.B.
        • Levine J.D.
        Hypotonicity induces TRPV4-mediated nociception in rat.
        Neuron. 2003; 39: 497-511
        • Alvarez P.
        • Bogen O.
        • Levine J.D.
        Nociceptor interleukin 33 receptor/ST2 signaling in vibration-induced muscle oain in the rat.
        J Pain. 2020; 21: 506-512
        • Alvarez P.
        • Ferrari L.F.
        • Levine J.D.
        Muscle pain in models of chemotherapy-induced and alcohol-induced peripheral neuropathy.
        Ann Neurol. 2011; 70: 101-109
        • Alvarez P.
        • Bogen O.
        • Levine J.D.
        Interleukin 6 decreases nociceptor expression of the potassium channel KV1.4 in a rat model of hand–arm vibration syndrome.
        Pain. 2019; 160: 1876-1882
        • Alvarez P.
        • Green P.G.
        • Levine J.D.
        Role for monocyte chemoattractant protein-1 in the induction of chronic muscle pain in the rat.
        Pain. 2014; 155: 1161-1167
        • Anderson E.O.
        • Schneider E.R.
        • Matson J.D.
        • Gracheva E.O.
        • Bagriantsev S.N.
        TMEM150C/Tentonin3 is a regulator of mechano-gated ion channels.
        Cell Rep. 2018; 23: 701-708
        • Apfel S.C.
        • Lipton R.B.
        • Arezzo J.C.
        • Kessler J.A.
        Nerve growth factor prevents toxic neuropathy in mice.
        Ann Neurol. 1991; 29: 87-90
        • Araldi D.
        • Bogen O.
        • Green P.G.
        • Levine J.D.
        Role of nociceptor toll-like receptor 4 (TLR4) in opioid-induced hyperalgesia and hyperalgesic priming.
        J Neurosci. 2019; 39: 6414-6424
        • Beaulieu-Laroche L.
        • Christin M.
        • Donoghue A.
        • Agosti F.
        • Yousefpour N.
        • Petitjean H.
        • Davidova A.
        • Stanton C.
        • Khan U.
        • Dietz C.
        • Faure E.
        • Fatima T.
        • MacPherson A.
        • Mouchbahani-Constance S.
        • Bisson D.G.
        • Haglund L.
        • Ouellet J.A.
        • Stone L.S.
        • Samson J.
        • Smith M.J.
        • Ask K.
        • Ribeiro-da-Silva A.
        • Blunck R.
        • Poole K.
        • Bourinet E.
        • Sharif-Naeini R.
        TACAN is an ion channel involved in sensing mechanical pain.
        Cell. 2020; 180: 956-967
        • Beurg M.
        • Kim K.X.
        • Fettiplace R.
        Conductance and block of hair-cell mechanotransducer channels in transmembrane channel-like protein mutants.
        J Gen Physiol. 2014; 144: 55-69
        • Binshtok A.M.
        • Wang H.
        • Zimmermann K.
        • Amaya F.
        • Vardeh D.
        • Shi L.
        • Brenner G.J.
        • Ji R.R.
        • Bean B.P.
        • Woolf C.J.
        • Samad T.A.
        Nociceptors are interleukin-1beta sensors.
        J Neurosci. 2008; 28: 14062-14073
        • Bogen O.
        • Alessandri-Haber N.
        • Chu C.
        • Gear R.W.
        • Levine J.D.
        Generation of a pain memory in the primary afferent nociceptor triggered by PKCε activation of CPEB.
        J Neurosci. 2012; 32: 2018-2026
        • Boyer A.E.
        • Quinn C.P.
        • Beesley C.A.
        • Gallegos-Candela M.
        • Marston C.K.
        • Cronin L.X.
        • Lins R.C.
        • Stoddard R.A.
        • Li H.
        • Schiffer J.
        • Hossain M.J.
        • Chakraborty A.
        • Rahman M.
        • Luby S.P.
        • Shieh W.J.
        • Zaki S.
        • Barr J.R.
        • Hoffmaster A.R.
        Lethal factor toxemia and anti-protective antigen antibody activity in naturally acquired cutaneous anthrax.
        J Infect Dis. 2011; 204: 1321-1327
        • Cavaletti G.
        • Bogliun G.
        • Crespi V.
        • Marzorati L.
        • Zincone A.
        • Marzola M.
        • Rota S.
        • Galli A.
        • Tredici P.
        • Tredici G.
        Neurotoxicity and ototoxicity of cisplatin plus paclitaxel in comparison to cisplatin plus cyclophosphamide in patients with epithelial ovarian cancer.
        J Clin Oncol. 1997; 15: 199-206
        • Cavaletti G.
        • Tredici G.
        • Braga M.
        • Tazzari S.
        Experimental peripheral neuropathy induced in adult rats by repeated intraperitoneal administration of taxol.
        Exp Neurol. 1995; 133: 64-72
        • Cavanaugh D.J.
        • Lee H.
        • Lo L.
        • Shields S.D.
        • Zylka M.J.
        • Basbaum A.I.
        • Anderson D.J.
        Distinct subsets of unmyelinated primary sensory fibers mediate behavioral responses to noxious thermal and mechanical stimuli.
        Proc Natl Acad Sci U S A. 2009; 106: 9075-9080
        • Chalfie M.
        Neurosensory mechanotransduction.
        Nat Rev Mol Cell Biol. 2009; 10: 44-52
        • Cheng W.
        • Sun C.
        • Zheng J.
        Heteromerization of TRP channel subunits: Extending functional diversity.
        Protein Cell. 2010; 1: 802-810
        • Cliffer K.D.
        • Siuciak J.A.
        • Carson S.R.
        • Radley H.E.
        • Park J.S.
        • Lewis D.R.
        • Zlotchenko E.
        • Nguyen T.
        • Garcia K.
        • Tonra J.R.
        • Stambler N.
        • Cedarbaum J.M.
        • Bodine S.C.
        • Lindsay R.M.
        • DiStefano P.S.
        Physiological characterization of Taxol-induced large-fiber sensory neuropathy in the rat.
        Ann Neurol. 1998; 43: 46-55
        • Coste B.
        • Mathur J.
        • Schmidt M.
        • Earley T.J.
        • Ranade S.
        • Petrus M.J.
        • Dubin A.E.
        • Patapoutian A.
        Piezo1 and Piezo2 are essential components of distinct mechanically activated cation channels.
        Science. 2010; 330: 55-60
        • Costigan M.
        • Scholz J.
        • Woolf C.J.
        Neuropathic pain: A maladaptive response of the nervous system to damage.
        Annu Rev Neurosci. 2009; 32: 1-32
        • Dina O.A.
        • Chen X.
        • Reichling D.
        • Levine J.D.
        Role of protein kinase Cε and protein kinase A in a model of paclitaxel-induced painful peripheral neuropathy in the rat.
        Neuroscience. 2001;
        • Dina O.A.
        • Parada C.A.
        • Yeh J.
        • Chen X.
        • McCarter G.C.
        • Levine J.D.
        Integrin signaling in inflammatory and neuropathic pain in the rat.
        Eur J Neurosci. 2004; 19: 634-642
        • Ferrari L.F.
        • Araldi D.
        • Bogen O.
        • Green P.G.
        • Levine J.D.
        Systemic morphine produces dose-dependent nociceptor-mediated biphasic changes in nociceptive threshold and neuroplasticity.
        Neuroscience. 2019; 398: 64-75
        • Ferrari L.F.
        • Araldi D.
        • Green P.G.
        • Levine J.D.
        Marked sexual dimorphism in neuroendocrine mechanisms for the exacerbation of paclitaxel-induced painful peripheral neuropathy by stress.
        Pain. 2020; 161: 865-874
        • Ferrari L.F.
        • Chum A.
        • Bogen O.
        • Reichling D.B.
        • Levine J.D.
        Role of Drp1, a key mitochondrial fission protein, in neuropathic pain.
        J Neurosci. 2011; 31: 11404-11410
        • Ferrari L.F.
        • Khomula E.V.
        • Araldi D.
        • Levine J.D.
        Marked sexual dimorphism in the role of the ryanodine receptor in a model of pain chronification in the rat.
        Sci Rep. 2016; 6: 31221
        • Ferrari L.F.
        • Khomula E.V.
        • Araldi D.
        • Levine J.D.
        CD44 signaling mediates high molecular weight hyaluronan-induced antihyperalgesia.
        J Neurosci. 2018; 38: 308-321
        • Ferrari L.F.
        • Bogen O.
        • Green P.
        • Levine J.D.
        Contribution of Piezo2 to endothelium-dependent pain.
        Mol Pain. 2015; 11: 1-8
        • Gold M.S.
        • Gebhart G.F.
        Nociceptor sensitization in pain pathogenesis.
        Nat Med. 2010; 16: 1248-1257
        • Hamers F.P.
        • Pette C.
        • Neijt J.P.
        • Gispen W.H.
        The ACTH-(4-9) analog, ORG 2766, prevents taxol-induced neuropathy in rats.
        Eur J Pharmacol. 1993; 233: 177-178
        • He B.H.
        • Christin M.
        • Mouchbahani-Constance S.
        • Davidova A.
        • Sharif-Naeini R.
        Mechanosensitive ion channels in articular nociceptors drive mechanical allodynia in osteoarthritis.
        Osteoarthritis Cartilage. 2017; 25: 2091-2099
        • Ikeda R.
        • Cha M.
        • Ling J.
        • Jia Z.
        • Coyle D.
        • Gu J.G
        Merkel cells transduce and encode tactile stimuli to drive Aβ-afferent impulses.
        Cell. 2014; 157: 664-675
        • Joseph E.K.
        • Chen X.
        • Bogen O.
        • Levine J.D.
        Oxaliplatin acts on IB4-positive nociceptors to induce an oxidative stress-dependent acute painful peripheral neuropathy.
        J Pain. 2008; 9: 463-472
        • Kawashima Y.
        • Kurima K.
        • Pan B.
        • Griffith A.J.
        • Holt J.R.
        Transmembrane channel-like (TMC) genes are required for auditory and vestibular mechanosensation.
        Pflugers Arch. 2015; 467: 85-94
        • Kim S.E.
        • Coste B.
        • Chadha A.
        • Cook B.
        • Patapoutian A.
        The role of Drosophila Piezo in mechanical nociception.
        Nature. 2012; 483: 209-212
        • Lai D.
        • Weng S.
        • Wang C.
        • Qi L.
        • Yu C.
        • Fu L.
        • Chen W.
        Small antisense RNA to cyclin D1 generated by pre-tRNA splicing inhibits growth of human hepatoma cells.
        FEBS Lett. 2004; 576: 481-486
        • Lai J.
        • Gold M.S.
        • Kim C.S.
        • Bian D.
        • Ossipov M.H.
        • Hunter J.C.
        • Porreca F.
        Inhibition of neuropathic pain by decreased expression of the tetrodotoxin-resistant sodium channel, NaV1.8.
        Pain. 2002; 95: 143-152
        • Li Fraine S.
        • Patel A.
        • Duprat F.
        • Sharif-Naeini R.
        Dynamic regulation of TREK1 gating by polycystin 2 via a filamin a-mediated cytoskeletal mechanism.
        Sci Rep. 2017; 7: 17403
        • Li M.F.
        • Hsiao C.H.
        • Chen Y.L.
        • Huang W.Y.
        • Lee Y.H.
        • Huang H.N.
        • Lien H.C.
        Human herpesvirus 8-associated lymphoma mimicking cutaneous anaplastic large T-cell lymphoma in a patient with human immunodeficiency virus infection.
        J Cutan Pathol. 2012; 39: 274-278
        • McQueen D.S.
        • Iggo A.
        • Birrell G.J.
        • Grubb B.D.
        Effects of paracetamol and aspirin on neural activity of joint mechanonociceptors in adjuvant arthritis.
        Br J Pharmacol. 1991; 104: 178-182
        • Mestre C.
        • Pélissier T.
        • Fialip J.
        • Wilcox G.
        • Eschalier A.
        A method to perform direct transcutaneous intrathecal injection in rats.
        J Pharmacol Toxicol Methods. 1994; 32: 197-200
        • Neogi T.
        • Guermazi A.
        • Roemer F.
        • Nevitt M.C.
        • Scholz J.
        • Arendt-Nielsen L.
        • Woolf C.
        • Niu J.
        • Bradley L.A.
        • Quinn E.
        • Law L.F.
        Association of joint inflammation with pain sensitization in knee osteoarthritis: The Multicenter Osteoarthritis Study.
        Arthritis Rheumatol. 2016; 68: 654-661
        • Nilius B.
        • Owsianik G.
        The transient receptor potential family of ion channels.
        Genome Biol. 2011; 12: 218
        • Okun A.
        • Liu P.
        • Davis P.
        • Ren J.
        • Remeniuk B.
        • Brion T.
        • Ossipov M.H.
        • Xie J.
        • Dussor G.O.
        • King T.
        • Porreca F.
        Afferent drive elicits ongoing pain in a model of advanced osteoarthritis.
        Pain. 2012; 153: 924-933
        • Oliveira-Fusaro M.C.G.
        • Zanoni C.I.S.
        • Dos Santos G.G.
        • Manzo L.P.
        • Araldi D.
        • Bonet I.J.M.
        • Tambeli C.H.
        • Dias E.V.
        • Parada C.A.
        Antihyperalgesic effect of CB1 receptor activation involves the modulation of P2X3 receptor in the primary afferent neuron.
        Eur J Pharmacol. 2017; 798: 113-121
        • Parada C.A.
        • Yeh J.J.
        • Reichling D.B.
        • Levine J.D.
        Transient attenuation of protein kinase Cε can terminate a chronic hyperalgesic state in the rat.
        Neuroscience. 2003; 120: 219-226
        • Quanhong Z.
        • Ying X.
        • Moxi C.
        • Tao X.
        • Jing W.
        • Xin Z.
        • Li W.
        • Derong C.
        • Xiaoli Z.
        • Wei J.
        Intrathecal PLC(β3) oligodeoxynucleotides antisense potentiates acute morphine efficacy and attenuates chronic morphine tolerance.
        Brain Res. 2012; 1472: 38-44
        • Ranade S.S.
        • Syeda R.
        • Patapoutian A.
        Mechanically activated ion channels.
        Neuron. 2015; 87: 1162-1179
        • Ranade S.S.
        • Woo S.H.
        • Dubin A.E.
        • Moshourab R.A.
        • Wetzel C.
        • Petrus M.
        • Mathur J.
        • Bégay V.
        • Coste B.
        • Mainquist J.
        • Wilson A.J.
        • Francisco A.G.
        • Reddy K.
        • Qiu Z.
        • Wood J.N.
        • Lewin G.R.
        • Patapoutian A.
        Piezo2 is the major transducer of mechanical forces for touch sensation in mice.
        Nature. 2014; 516: 121-125
        • Randall L.O.
        • Selitto J.J.
        A method for measurement of analgesic activity on inflamed tissue.
        Arch Int Pharmacodyn Ther. 1957; 111: 409-419
        • Schäfers M.
        • Geis C.
        • Svensson C.I.
        • Luo Z.D.
        • Sommer C.
        Selective increase of tumour necrosis factor-alpha in injured and spared myelinated primary afferents after chronic constrictive injury of rat sciatic nerve.
        Eur J Neurosci. 2003; 17: 791-804
        • Schaible H.G.
        Nociceptive neurons detect cytokines in arthritis.
        Arthritis Res Ther. 2014; 16: 470
        • Sharif-Naeini R.
        • Folgering J.H.
        • Bichet D.
        • Duprat F.
        • Lauritzen I.
        • Arhatte M.
        • Jodar M.
        • Dedman A.
        • Chatelain F.C.
        • Schulte U.
        • Retailleau K.
        • Loufrani L.
        • Patel A.
        • Sachs F.
        • Delmas P.
        • Peters D.J.
        • Honoré E.
        Polycystin-1 and -2 dosage regulates pressure sensing.
        Cell. 2009; 139: 587-596
        • Song M.J.
        • Wang Y.Q.
        • Wu G.C.
        Additive anti-hyperalgesia of electroacupuncture and intrathecal antisense oligodeoxynucleotide to interleukin-1 receptor type I on carrageenan-induced inflammatory pain in rats.
        Brain Res Bull. 2009; 78: 335-341
        • Su L.
        • Wang C.
        • Yu Y.H.
        • Ren Y.Y.
        • Xie K.L.
        • Wang G.L.
        Role of TRPM8 in dorsal root ganglion in nerve injury-induced chronic pain.
        BMC Neurosci. 2011; 12: 120
        • Sun J.L.
        • Xiao C.
        • Lu B.
        • Zhang J.
        • Yuan X.Z.
        • Chen W.
        • Yu L.N.
        • Zhang F.J.
        • Chen G.
        • Yan M.
        CX3CL1/CX3CR1 regulates nerve injury-induced pain hypersensitivity through the ERK5 signaling pathway.
        J Neurosci Res. 2013; 91: 545-553
        • Taiwo Y.O.
        • Coderre T.J.
        • Levine J.D.
        The contribution of training to sensitivity in the nociceptive paw-withdrawal test.
        Brain Res. 1989; 487: 148-151
        • Taiwo Y.O.
        • Levine J.D.
        Prostaglandin effects after elimination of indirect hyperalgesic mechanisms in the skin of the rat.
        Brain Res. 1989; 492: 397-399
        • Woo S.H.
        • Lukacs V.
        • de Nooij J.C.
        • Zaytseva D.
        • Criddle C.R.
        • Francisco A.
        • Jessell T.M.
        • Wilkinson K.A.
        • Patapoutian A.
        Piezo2 is the principal mechanotransduction channel for proprioception.
        Nat Neurosci. 2015; 18: 1756-1762
        • Woo S.H.
        • Ranade S.
        • Weyer A.D.
        • Dubin A.E.
        • Baba Y.
        • Qiu Z.
        • Petrus M.
        • Miyamoto T.
        • Reddy K.
        • Lumpkin E.A.
        • Stucky C.L.
        • Patapoutian A.
        Piezo2 is required for Merkel-cell mechanotransduction.
        Nature. 2014; 509: 622-626