Abstract
Chronic pain is the predominant symptom that drives temporomandibular joint osteoarthritis (TMJOA) patients to seek medical care; however, currently used treatment modalities remain less effective. This study aimed to investigate chronic pain and the peripheral and central responses in monoiodoacetate (MIA)-induced TMJOA rats. First, the appropriate dose of MIA was determined based on pain behavior assessment in rats. Alterations of the condylar structure in TMJOA rats were evaluated by histological staining and micro-computed tomography (micro-CT). Second, the period of TMJOA chronic pain was further explored by assessing the numbers of glial fibrillary acidic protein (GFAP)-positive astrocytes and ionized calcium-binding adaptor molecule 1 (IBA-1)-positive microglia in the trigeminal spinal nucleus (TSN) and performing nonsteroidal anti-inflammatory drug (NSAID) efficacy experiments. Finally, the expression of neurofilament 200 (NF200), calcitonin gene-related peptide (CGRP), and isolectin B4 (IB4) in the trigeminal ganglion (TG) and TSN was assessed by immunofluorescence. MIA at 4 mg/kg was considered an appropriate dose. Gradual MIA-induced alterations of the condylar structure were correlated with temporomandibular joint (TMJ) pain. The numbers of GFAP- and IBA-1-positive cells were increased at 2, 3, and 4 weeks after MIA injection. NSAIDs failed to alleviate pain behavior 10 days after MIA injection. CGRP and IB4 levels in the TG and TSN were upregulated at 2 and 4 weeks. These results suggest that TMJOA-related chronic pain emerged 2 weeks after MIA injection. CGRP- and IB4-positive afferents in both the peripheral and central nervous systems may be involved in MIA-induced TMJOA-related chronic pain in rats.
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References
Alvarez P, Chen X, Bogen O, Green PG, Levine JD (2012) IB4(+) nociceptors mediate persistent muscle pain induced by GDNF. J Neurophysiol 108:2545–2553. https://doi.org/10.1152/jn.00576.2012
Basbaum AI, Bautista DM, Scherrer G, Julius D (2009) Cellular and molecular mechanisms of pain. Cell 139:267–284. https://doi.org/10.1016/j.cell.2009.09.028
Calvo M, Bennett DL (2012) The mechanisms of microgliosis and pain following peripheral nerve injury. Exp Neurol 234:271–282. https://doi.org/10.1016/j.expneurol.2011.08.018
Cirillo G et al (2010) Intrathecal NGF administration reduces reactive astrocytosis and changes neurotrophin receptors expression pattern in a rat model of neuropathic pain. Cell Mol Neurobiol 30:51–62. https://doi.org/10.1007/s10571-009-9430-2
Clements KM, Ball AD, Jones HB, Brinckmann S, Read SJ, Murray F (2009) Cellular and histopathological changes in the infrapatellar fat pad in the monoiodoacetate model of osteoarthritis pain. Osteoarthr Cartil 17:805–812. https://doi.org/10.1016/j.joca.2008.11.002
Coskun U, Candirli C, Kerimoglu G, Taskesen F (2019) Effect of platelet-rich plasma on temporomandibular joint cartilage wound healing: experimental study in rabbits. J Craniomaxillofac Surg 47:357–364. https://doi.org/10.1016/j.jcms.2018.12.004
Fernihough J et al (2004) Pain related behaviour in two models of osteoarthritis in the rat knee. Pain 112:83–93. https://doi.org/10.1016/j.pain.2004.08.004
Ferreira-Gomes J, Adaes S, Sarkander J, Castro-Lopes JM (2010) Phenotypic alterations of neurons that innervate osteoarthritic joints in rats. Arthritis Rheum 62:3677–3685. https://doi.org/10.1002/art.27713
Garrison CJ, Dougherty PM, Kajander KC, Carlton SM (1991) Staining of glial fibrillary acidic protein (GFAP) in lumbar spinal cord increases following a sciatic nerve constriction injury. Brain Res 565:1–7. https://doi.org/10.1016/0006-8993(91)91729-k
Gowler PRW, Li L, Woodhams SG, Bennett AJ, Suzuki R, Walsh DA, Chapman V (2019) Peripheral brain derived neurotrophic factor contributes to chronic osteoarthritis joint pain in two animal models of osteoarthritis. Osteoarthr Cartil 26:S15
Guler N, Kurkcu M, Duygu G, Cam B (2011) Sodium iodoacetate induced osteoarthrosis model in rabbit temporomandibular joint: CT and histological study (part I). Int J Oral Maxillofac Surg 40:1289–1295. https://doi.org/10.1016/j.ijom.2011.07.908
Gupta PK et al (2016) Efficacy and safety of adult human bone marrow-derived, cultured, pooled, allogeneic mesenchymal stromal cells (Stempeucel(R)): preclinical and clinical trial in osteoarthritis of the knee joint. Arthritis Res Ther 18:301. https://doi.org/10.1186/s13075-016-1195-7
Guzman RE, Evans MG, Bove S, Morenko B, Kilgore K (2003) Mono-iodoacetate-induced histologic changes in subchondral bone and articular cartilage of rat femorotibial joints: an animal model of osteoarthritis. Toxicol Pathol 31:619–624. https://doi.org/10.1080/01926230390241800
Hald A (2009) Spinal astrogliosis in pain models: cause and effects. Cell Mol Neurobiol 29:609–619. https://doi.org/10.1007/s10571-009-9390-6
Hawker GA et al (2008) Understanding the pain experience in hip and knee osteoarthritis–an OARSI/OMERACT initiative. Osteoarthr Cartil 16:415–422. https://doi.org/10.1016/j.joca.2007.12.017
Ji RR, Berta T, Nedergaard M (2013) Glia and pain: is chronic pain a gliopathy? Pain 154(Suppl 1):S10–S28. https://doi.org/10.1016/j.pain.2013.06.022
Ji RR, Xu ZZ, Gao YJ (2014) Emerging targets in neuroinflammation-driven chronic pain. Nat Rev Drug Discov 13:533–548. https://doi.org/10.1038/nrd4334
Jiao K, Niu LN, Wang MQ, Dai J, Yu SB, Liu XD, Wang J (2011) Subchondral bone loss following orthodontically induced cartilage degradation in the mandibular condyles of rats. Bone 48:362–371
Kameoka S, Matsumoto K, Kai Y, Yonehara Y, Arai Y, Honda K (2010a) Establishment of temporomandibular joint puncture technique in rats using in vivo micro-computed tomography (R_mCT(R)). Dentomaxillofac Radiol 39:441–445. https://doi.org/10.1259/dmfr/37174063
Kameoka S, Matsumoto K, Kai Y, Yonehara Y, Honda K (2010b) Establishment of temporomandibular joint puncture technique in rats using in vivo micro-computed tomography (R_mCT?). Dento Maxillo Facial Radiol 39:441–445
La JH, Feng B, Kaji K, Schwartz ES, Gebhart GF (2016) Roles of isolectin B4-binding afferents in colorectal mechanical nociception. Pain 157:348–354. https://doi.org/10.1097/j.pain.0000000000000380
Li ZW, Wu B, Ye P, Tan ZY, Ji YH (2016) Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats. J Headache Pain 17:90. https://doi.org/10.1186/s10194-016-0685-y
Miyagi M et al (2017) Efficacy of nerve growth factor antibody in a knee osteoarthritis pain model in mice. BMC Musculoskelet Disord 18:428. https://doi.org/10.1186/s12891-017-1792-x
Mujakperuo HR, Watson M, Morrison R, Macfarlane TV (2010) Pharmacological interventions for pain in patients with temporomandibular disorders. Cochrane Database Syst Rev. https://doi.org/10.1002/14651858.CD004715.pub2
Neugebauer V, Rumenapp P, Schaible HG (1996) Calcitonin gene-related peptide is involved in the spinal processing of mechanosensory input from the rat’s knee joint and in the generation and maintenance of hyperexcitability of dorsal horn-neurons during development of acute inflammation. Neuroscience 71:1095–1109. https://doi.org/10.1016/0306-4522(95)00473-4
Nwosu LN, Mapp PI, Chapman V, Walsh DA (2016) Relationship between structural pathology and pain behaviour in a model of osteoarthritis (OA). Osteoarthr Cartil 24:1910–1917. https://doi.org/10.1016/j.joca.2016.06.012
Okun A et al (2012) Afferent drive elicits ongoing pain in a model of advanced osteoarthritis. Pain 153:924–933. https://doi.org/10.1016/j.pain.2012.01.022
Oroszova Z, Hricova L, Stropkovska A, Lukacova N, Pavel J (2017) The characterization of AT1 expression in the dorsal root ganglia after chronic constriction injury. Cell Mol Neurobiol 37:545–554. https://doi.org/10.1007/s10571-016-0396-6
Perry MJ, Lawson SN, Robertson J (1991) Neurofilament immunoreactivity in populations of rat primary afferent neurons: a quantitative study of phosphorylated and non-phosphorylated subunits. J Neurocytol 20:746–758
Philpott HT, McDougall JJ (2020) Combatting joint pain and inflammation by dual inhibition of monoacylglycerol lipase and cyclooxygenase-2 in a rat model of osteoarthritis. Arthritis Res Ther. https://doi.org/10.1186/s13075-020-2096-3
Sagar DR et al (2011) The contribution of spinal glial cells to chronic pain behaviour in the monosodium iodoacetate model of osteoarthritic pain. Mol Pain 7:88. https://doi.org/10.1186/1744-8069-7-88
Sannajust S et al (2019) Females have greater susceptibility to develop ongoing pain and central sensitization in a rat model of temporomandibular joint pain. Pain 160:2036–2049. https://doi.org/10.1097/j.pain.0000000000001598
Schaible HG, Ebersberger A, Von Banchet GS (2002) Mechanisms of pain in arthritis. Ann N Y Acad Sci 966:343–354. https://doi.org/10.1111/j.1749-6632.2002.tb04234.x
Schiffman E et al (2014) Diagnostic criteria for temporomandibular disorders (DC/TMD) for clinical and research applications: recommendations of the International RDC/TMD consortium network* and orofacial pain special interest groupdagger. J Oral Facial Pain Headache 28:6–27. https://doi.org/10.11607/jop.1151
Scrivani SJ, Keith DA, Kaban LB (2008) Temporomandibular disorders. N Engl J Med 359:2693–2705. https://doi.org/10.1056/NEJMra0802472
Senye M, Mir CF, Morton S, Thie NM (2012) Topical nonsteroidal anti-inflammatory medications for treatment of temporomandibular joint degenerative pain: a systematic review. J Orofac Pain 26:26–32
Tanaka E, Detamore MS, Mercuri LG (2008) Degenerative disorders of the temporomandibular joint: etiology, diagnosis, and treatment. J Dent Res 87:296–307. https://doi.org/10.1177/154405910808700406
Taves S, Berta T, Chen G, Ji RR (2013) Microglia and spinal cord synaptic plasticity in persistent pain. Neural Plast 2013:753656. https://doi.org/10.1155/2013/753656
Vermeirsch H, Biermans R, Salmon PL, Meert TF (2007) Evaluation of pain behavior and bone destruction in two arthritic models in guinea pig and rat. Pharmacol Biochem Behav 87:349–359. https://doi.org/10.1016/j.pbb.2007.05.010
Wang XD et al (2012) Progression of cartilage degradation, bone resorption and pain in rat temporomandibular joint osteoarthritis induced by injection of iodoacetate. PLoS ONE 7(9):e45036
Wang XD, Zhang JN, Gan YH, Zhou YH (2015) Current understanding of pathogenesis and treatment of TMJ osteoarthritis. J Dent Res 94:666–673. https://doi.org/10.1177/0022034515574770
Woolf CJ, Shortland P, Coggeshall RE (1992) Peripheral nerve injury triggers central sprouting of myelinated afferents. Nature 355:75–78. https://doi.org/10.1038/355075a0
Wright EF (2010) Manual of temporomandibular disorders. Br Dent J 209:322
Xu L, Jiang H, Feng Y, Cao P, Ke J, Long X (2019) Peripheral and central substance P expression in rat CFA-induced TMJ synovitis pain. Mol Pain 15:2069297180. https://doi.org/10.1177/1744806919866340
Xu ZZ et al (2015) Inhibition of mechanical allodynia in neuropathic pain by TLR5-mediated A-fiber blockade. Nat Med 21:1326–1331. https://doi.org/10.1038/nm.3978
Yamashita T, Cavanaugh JM, El-Bohy AA, Getchell TV, King AI (1990) Mechanosensitive afferent units in the lumbar facet joint. J Bone Joint Surg Am 72:865–870
Zarb GA, Carlsson GE (1999) Temporomandibular disorders osteoarthritis. J Orofacial Pain 13:295–306
Zhang L et al (2019) Chronic pain induces nociceptive neurogenesis in dorsal root ganglia from Sox2-positive satellite cells. Glia 67:1062–1075. https://doi.org/10.1002/glia.23588
Zhang L, Hoff AO, Wimalawansa SJ, Cote GJ, Westlund KN (2001) Arthritic calcitonin/α calcitonin gene-related peptide knockout mice have reduced nociceptive hypersensitivity. Pain 89:265–273
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This study was funded by the National Science Foundation of China (Grant Numbers 81771100 and 81870789).
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This study was designed by XL and JK. Data were collected and analyzed by HJ, LX, WL, and MX. HJ drafted the first manuscript. The article was critically revised by XL, JK, and HJ. All authors read and approved the final manuscript.
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Jiang, H., Xu, L., Liu, W. et al. Chronic Pain Causes Peripheral and Central Responses in MIA-Induced TMJOA Rats. Cell Mol Neurobiol 42, 1441–1451 (2022). https://doi.org/10.1007/s10571-020-01033-8
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DOI: https://doi.org/10.1007/s10571-020-01033-8