Transient receptor potential melastatin 8 contributes to the interleukin-33-mediated cold allodynia in a mouse model of neuropathic pain.
Journal
Pain
ISSN: 1872-6623
Titre abrégé: Pain
Pays: United States
ID NLM: 7508686
Informations de publication
Date de publication:
08 Aug 2024
08 Aug 2024
Historique:
received:
06
01
2024
accepted:
17
06
2024
medline:
12
8
2024
pubmed:
12
8
2024
entrez:
12
8
2024
Statut:
aheadofprint
Résumé
Cold allodynia is a common complaint of patients suffering from neuropathic pain initiated by peripheral nerve injury. However, the mechanisms that drive neuropathic cold pain remain elusive. In this study, we show that the interleukin (IL)-33/ST2 signaling in the dorsal root ganglion (DRG) is a critical contributor to neuropathic cold pain by interacting with the cold sensor transient receptor potential melastatin 8 (TRPM8). By using the St2-/- mice, we demonstrate that ST2 is required for the generation of nociceptor hyperexcitability and cold allodynia in a mouse model of spared nerve injury (SNI). Moreover, the selective elimination of ST2 function from the Nav1.8-expressing nociceptor markedly suppresses SNI-induced cold allodynia. Consistent with the loss-of-function studies, intraplantar injection of recombinant IL-33 (rIL-33) is sufficient to induce cold allodynia. Mechanistically, ST2 is co-expressed with TRPM8 in both mouse and human DRG neurons and rIL-33-induced Ca2+ influx in mouse DRG neurons through TRPM8. Co-immunoprecipitation assays further reveal that ST2 interacts with TRPM8 in DRG neurons. Importantly, rIL-33-induced cold allodynia is abolished by pharmacological inhibition of TRPM8 and genetic ablation of the TRPM8-expressing neurons. Thus, our findings suggest that the IL-33/ST2 signaling mediates neuropathic cold pain through downstream cold-sensitive TRPM8 channels, thereby identifying a potential analgesic target for the treatment of neuropathic cold pain.
Identifiants
pubmed: 39132923
doi: 10.1097/j.pain.0000000000003346
pii: 00006396-990000000-00679
doi:
Types de publication
Journal Article
Langues
eng
Sous-ensembles de citation
IM
Subventions
Organisme : STI2030 - Major Projects
ID : 2022ZD0204700
Organisme : National Natural Science Foundation of China
ID : 82271248
Organisme : National Natural Science Foundation of China
ID : 82204830
Organisme : National Natural Science Foundation of China
ID : 82271258
Organisme : National Natural Science Foundation of China
ID : 81771202
Organisme : Shanghai Sailing Program
ID : 21YF1447500
Informations de copyright
Copyright © 2024 International Association for the Study of Pain.
Références
Aierken A, Xie YK, Dong W, Apaer A, Lin JJ, Zhao Z, Yang S, Xu ZZ, Yang F. Rational design of a modality-specific inhibitor of TRPM8 channel against oxaliplatin-induced cold allodynia. Adv Sci (Weinh) 2021;8:e2101717.
Al-Mazidi S, Alotaibi M, Nedjadi T, Chaudhary A, Alzoghaibi M, Djouhri L. Blocking of cytokines signalling attenuates evoked and spontaneous neuropathic pain behaviours in the paclitaxel rat model of chemotherapy-induced neuropathy. Eur J Pain (London, England) 2018;22:810–21.
Baekkevold ES, Roussigné M, Yamanaka T, Johansen FE, Jahnsen FL, Amalric F, Brandtzaeg P, Erard M, Haraldsen G, Girard JP. Molecular characterization of NF-HEV, a nuclear factor preferentially expressed in human high endothelial venules. Am J Pathol 2003;163:69–79.
Basbaum AI, Bautista DM, Scherrer G, Julius D. Cellular and molecular mechanisms of pain. Cell 2009;139:267–84.
Cao L, Yue X, Zhao Y, Du L, Xie Z, Yuan Y, Zhang S, Li F, Feng J, Hu H. Mechanisms of broad-band UVB irradiation‒induced itch in mice. J Invest Dermatol 2021;141:2499–508.e3.
Cao S, Li Q, Hou J, Li Z, Cao X, Liu X, Qin B. Intrathecal TRPM8 blocking attenuates cold hyperalgesia via PKC and NF-κB signaling in the dorsal root ganglion of rats with neuropathic pain. J Pain Res 2019;12:1287–96.
Chen G, Kim YH, Li H, Luo H, Liu DL, Zhang ZJ, Lay M, Chang W, Zhang YQ, Ji RR. PD-L1 inhibits acute and chronic pain by suppressing nociceptive neuron activity via PD-1. Nat Neurosci 2017;20:917–26.
Colburn RW, Lubin ML, Stone DJ Jr., Wang Y, Lawrence D, D'Andrea MR, Brandt MR, Liu Y, Flores CM, Qin N. Attenuated cold sensitivity in TRPM8 null mice. Neuron 2007;54:379–86.
Descoeur J, Pereira V, Pizzoccaro A, Francois A, Ling B, Maffre V, Couette B, Busserolles J, Courteix C, Noel J, Lazdunski M, Eschalier A, Authier N, Bourinet E. Oxaliplatin-induced cold hypersensitivity is due to remodelling of ion channel expression in nociceptors. EMBO Mol Med 2011;3:266–78.
Ding X, Luo Y, Zhang X, Zheng H, Yang X, Yang X, Liu M. IL-33-driven ILC2/eosinophil axis in fat is induced by sympathetic tone and suppressed by obesity. J Endocrinol 2016;231:35–48.
Du L, Hu X, Yang W, Yasheng H, Liu S, Zhang W, Zhou Y, Cui W, Zhu J, Qiao Z, Maoying Q, Chu Y, Zhou H, Wang Y, Mi W. Spinal IL-33/ST2 signaling mediates chronic itch in mice through the astrocytic JAK2-STAT3 cascade. Glia 2019;67:1680–93.
Du LX, Wang YQ, Hua GQ, Mi WL. IL-33/ST2 pathway as a rational therapeutic target for CNS diseases. Neuroscience 2018;369:222–30.
Feng J, Hibberd TJ, Luo J, Yang P, Xie Z, Travis L, Spencer NJ, Hu H. Modification of neurogenic colonic motor behaviours by chemogenetic ablation of calretinin neurons. Front Cell Neurosci 2022;16:799717.
Gao TC, Wang CH, Wang YQ, Mi WL. IL-33/ST2 signaling in the pathogenesis of chronic pain and itch. Neuroscience 2023;529:16–22.
Han P, Liu S, Zhang M, Zhao J, Wang Y, Wu G, Mi W. Inhibition of spinal interlukin-33/ST2 signaling and downstream ERK and JNK pathways in electroacupuncture analgesia in formalin mice. PLoS One 2015;10:e0129576.
Hung AL, Lim M, Doshi TL. Targeting cytokines for treatment of neuropathic pain. Scand J Pain 2017;17:287–93.
Jensen TS, Finnerup NB. Allodynia and hyperalgesia in neuropathic pain: clinical manifestations and mechanisms. Lancet Neurol 2014;13:924–35.
Kashio M. Thermosensation involving thermo-TRPs. Mol Cell Endocrinol 2021;520:111089.
Knowlton WM, Bifolck-Fisher A, Bautista DM, McKemy DD. TRPM8, but not TRPA1, is required for neural and behavioral responses to acute noxious cold temperatures and cold-mimetics in vivo. PAIN 2010;150:340–50.
Knowlton WM, Daniels RL, Palkar R, McCoy DD, McKemy DD. Pharmacological blockade of TRPM8 ion channels alters cold and cold pain responses in mice. PLoS One 2011;6:e25894.
Knowlton WM, Palkar R, Lippoldt EK, McCoy DD, Baluch F, Chen J, McKemy DD. A sensory-labeled line for cold: TRPM8-expressing sensory neurons define the cellular basis for cold, cold pain, and cooling-mediated analgesia. J Neurosci 2013;33:2837–48.
Lan Z, Chen L, Feng J, Xie Z, Liu Z, Wang F, Liu P, Yue X, Du L, Zhao Y, Yang P, Luo J, Zhu Z, Hu X, Cao L, Lu P, Sah R, Lavine K, Kim B, Hu H. Mechanosensitive TRPV4 is required for crystal-induced inflammation. Ann Rheum Dis 2021;80:1604–14.
Liu B, Tai Y, Achanta S, Kaelberer MM, Caceres AI, Shao X, Fang J, Jordt SE. IL-33/ST2 signaling excites sensory neurons and mediates itch response in a mouse model of poison ivy contact allergy. Proc Natl Acad Sci U S A 2016;113:E7572–9.
Liu JQ, Hu TY, Diao KY, Yu D, Song YN, Mo LH, Yang G, Liu ZQ, Liu ZG, Yang PC. Cold stress promotes IL-33 expression in intestinal epithelial cells to facilitate food allergy development. Cytokine 2020;136:155295.
Liu S, Mi WL, Li Q, Zhang MT, Han P, Hu S, Mao-Ying QL, Wang YQ. Spinal IL-33/ST2 signaling contributes to neuropathic pain via neuronal CaMKII-CREB and astroglial JAK2-STAT3 cascades in mice. Anesthesiology 2015;123:1154–69.
Liu X, Xiao Y, Pan Y, Li H, Zheng SG, Su W. The role of the IL-33/ST2 axis in autoimmune disorders: friend or foe? Cytokine Growth Factor Rev 2019;50:60–74.
Liu Y, Abdel SamadO, Zhang L, Duan B, Tong Q, Lopes C, Ji RR, Lowell BB, Ma Q. VGLUT2-dependent glutamate release from nociceptors is required to sense pain and suppress itch. Neuron 2010;68:543–56.
Lolignier S, Gkika D, Andersson D, Leipold E, Vetter I, Viana F, Noël J, Busserolles J. New insight in cold pain: role of ion channels, modulation, and clinical perspectives. J Neurosci 2016;36:11435–9.
MacDonald DI, Wood JN, Emery EC. Molecular mechanisms of cold pain. Neurobiol Pain 2020;7:100044.
Marwaha L, Bansal Y, Singh R, Saroj P, Bhandari R, Kuhad A. TRP channels: potential drug target for neuropathic pain. Inflammopharmacology 2016;24:305–17.
McKemy DD. How cold is it? TRPM8 and TRPA1 in the molecular logic of cold sensation. Mol Pain 2005;1:16.
McKemy DD. Molecular basis of peripheral innocuous cold sensitivity. Handb Clin Neurol 2018;156:57–67.
Odegaard JI, Lee MW, Sogawa Y, Bertholet AM, Locksley RM, Weinberg DE, Kirichok Y, Deo RC, Chawla A. Perinatal licensing of thermogenesis by IL-33 and ST2. Cell 2017;171:1707.
Palkar R, Lippoldt EK, McKemy DD. The molecular and cellular basis of thermosensation in mammals. Curr Opin Neurobiol 2015;34:14–9.
Sałat K, Filipek B. Antinociceptive activity of transient receptor potential channel TRPV1, TRPA1, and TRPM8 antagonists in neurogenic and neuropathic pain models in mice. J Zhejiang Univ Sci B 2015;16:167–78.
Schmitz J, Owyang A, Oldham E, Song Y, Murphy E, McClanahan TK, Zurawski G, Moshrefi M, Qin J, Li X, Gorman DM, Bazan JF, Kastelein RA. IL-33, an interleukin-1-like cytokine that signals via the IL-1 receptor-related protein ST2 and induces T helper type 2-associated cytokines. Immunity 2005;23:479–90.
Sommer C, Leinders M, Üçeyler N. Inflammation in the pathophysiology of neuropathic pain. PAIN 2018;159:595–602.
Su L, Shu R, Song C, Yu Y, Wang G, Li Y, Liu C. Downregulations of TRPM8 expression and membrane trafficking in dorsal root ganglion mediate the attenuation of cold hyperalgesia in CCI rats induced by GFRα3 knockdown. Brain Res Bull 2017;135:8–24.
Takatori H, Makita S, Ito T, Matsuki A, Nakajima H. Regulatory mechanisms of IL-33-ST2-mediated allergic inflammation. Front Immunol 2018;9:2004.
Trier AM, Mack MR, Fredman A, Tamari M, Ver Heul AM, Zhao Y, Guo CJ, Avraham O, Ford ZK, Oetjen LK, Feng J, Dehner C, Coble D, Badic A, Joshita S, Kubo M, Gereau RWt, Alexander-Brett J, Cavalli V, Davidson S, Hu H, Liu Q, Kim BS. IL-33 signaling in sensory neurons promotes dry skin itch. J Allergy Clin Immunol 2022;149:1473–80.e6.
Wang Y, Wang X, Qi R, Lu Y, Tao Y, Jiang D, Sun Y, Jiang X, Liu C, Zhang Y, Tao J. Interleukin 33-mediated inhibition of A-type K(+) channels induces sensory neuronal hyperexcitability and nociceptive behaviors in mice. Theranostics 2022;12:2232–47.
Woolf CJ. Overcoming obstacles to developing new analgesics. Nat Med 2010;16:1241–7.
Yamaki S, Chau A, Gonzales L, McKemy DD. Nociceptive afferent phenotyping reveals that transient receptor potential ankyrin 1 promotes cold pain through neurogenic inflammation upstream of the neurotrophic factor receptor GFRα3 and the menthol receptor transient receptor potential melastatin 8. PAIN 2021;162:609–18.
Yin C, Liu B, Li Y, Li X, Wang J, Chen R, Tai Y, Shou Q, Wang P, Shao X, Liang Y, Zhou H, Mi W, Fang J, Liu B. IL-33/ST2 induces neutrophil-dependent reactive oxygen species production and mediates gout pain. Theranostics 2020;10:12189–203.
Yin K, Zimmermann K, Vetter I, Lewis RJ. Therapeutic opportunities for targeting cold pain pathways. Biochem Pharmacol 2015;93:125–40.
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 2016;30:54–65.
Zhao J, Zhang H, Liu SB, Han P, Hu S, Li Q, Wang ZF, Mao-Ying QL, Chen HM, Jiang JW, Wu GC, Mi WL, Wang YQ. Spinal interleukin-33 and its receptor ST2 contribute to bone cancer-induced pain in mice. Neuroscience 2013;253:172–82.
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. PAIN 1983;16:109–10.