Temporomandibular Joint Inflammation Activates Glial and Immune Cells in Both the Trigeminal Ganglia and in the Spinal Trigeminal Nucleus

Overview

Journal Mol Pain

Date 2010 Dec 15

PMID 21143950

Citations 51

Authors

Giovanni Villa

Stefania Ceruti

Matteo Zanardelli

Giulia Magni

Luc Jasmin

Peter T Ohara

Maria P Abbracchio

Affiliations

Soon will be listed here.

Abstract

Background: Glial cells have been shown to directly participate to the genesis and maintenance of chronic pain in both the sensory ganglia and the central nervous system (CNS). Indeed, glial cell activation has been reported in both the dorsal root ganglia and the spinal cord following injury or inflammation of the sciatic nerve, but no data are currently available in animal models of trigeminal sensitization. Therefore, in the present study, we evaluated glial cell activation in the trigeminal-spinal system following injection of the Complete Freund's Adjuvant (CFA) into the temporomandibular joint, which generates inflammatory pain and trigeminal hypersensitivity.

Results: CFA-injected animals showed ipsilateral mechanical allodynia and temporomandibular joint edema, accompanied in the trigeminal ganglion by a strong increase in the number of GFAP-positive satellite glial cells encircling neurons and by the activation of resident macrophages. Seventy-two hours after CFA injection, activated microglial cells were observed in the ipsilateral trigeminal subnucleus caudalis and in the cervical dorsal horn, with a significant up-regulation of Iba1 immunoreactivity, but no signs of reactive astrogliosis were detected in the same areas. Since the purinergic system has been implicated in the activation of microglial cells during neuropathic pain, we have also evaluated the expression of the microglial-specific P2Y12 receptor subtype. No upregulation of this receptor was detected following induction of TMJ inflammation, suggesting that any possible role of P2Y12 in this paradigm of inflammatory pain does not involve changes in receptor expression.

Conclusions: Our data indicate that specific glial cell populations become activated in both the trigeminal ganglia and the CNS following induction of temporomandibular joint inflammation, and suggest that they might represent innovative targets for controlling pain during trigeminal nerve sensitization.

Citing Articles

Mechanisms for Orofacial Pain: Roles of Immunomodulation, Metabolic Reprogramming, Oxidative Stress and Epigenetic Regulation.

Khan S, Tao F Biomedicines. 2025; 13(2).

PMID: 40002847 PMC: 11853523. DOI: 10.3390/biomedicines13020434.

The involvement of orexin-1 receptors in modulation of feeding and anxiety-like behavior in rats with complete Freund's adjuvant-induced temporomandibular joint disorder.

Hosaini M, Abbasnejad M, Kooshki R, Esmaeili-Mahani S, Raoof M, Naderi R Odontology. 2025; .

PMID: 39843662 DOI: 10.1007/s10266-024-01021-0.

Assessing the Causal Relationship Between Immune Cells and Temporomandibular Related Pain by Bi‑Directional Mendelian Randomization Analysis.

He J, Chen X J Pain Res. 2024; 17:3791-3800.

PMID: 39574830 PMC: 11579143. DOI: 10.2147/JPR.S486817.

Molecular Aspects Involved in the Mechanisms of Venom-Induced Hyperalgesia: Participation of NK1 Receptor and Glial Cells.

Bom A, Dias-Soares M, Correa R, Neves C, Hosch N, Lucena G Toxins (Basel). 2024; 16(4).

PMID: 38668612 PMC: 11053884. DOI: 10.3390/toxins16040187.

Bioactive Compound-Based Formulations: New Perspectives for the Management of Orofacial Pain.

Crescente G, Minervini G, Spagnuolo C, Moccia S Molecules. 2023; 28(1).

PMID: 36615298 PMC: 9822121. DOI: 10.3390/molecules28010106.

References

Inglis J, Nissim A, Lees D, Hunt S, Chernajovsky Y, Kidd B . The differential contribution of tumour necrosis factor to thermal and mechanical hyperalgesia during chronic inflammation. Arthritis Res Ther. 2005; 7(4):R807-16. PMC: 1175031. DOI: 10.1186/ar1743. View

Bereiter D, Okamoto K, Bereiter D . Effect of persistent monoarthritis of the temporomandibular joint region on acute mustard oil-induced excitation of trigeminal subnucleus caudalis neurons in male and female rats. Pain. 2005; 117(1-2):58-67. DOI: 10.1016/j.pain.2005.05.013. View

Lin T, Li K, Zhang F, Zhang Z, Light A, Fu K . Dissociation of spinal microglia morphological activation and peripheral inflammation in inflammatory pain models. J Neuroimmunol. 2007; 192(1-2):40-8. PMC: 2198900. DOI: 10.1016/j.jneuroim.2007.09.003. View

Iwata K, Tashiro A, Tsuboi Y, Imai T, Sumino R, Morimoto T . Medullary dorsal horn neuronal activity in rats with persistent temporomandibular joint and perioral inflammation. J Neurophysiol. 1999; 82(3):1244-53. DOI: 10.1152/jn.1999.82.3.1244. View

Takeda M, Takahashi M, Matsumoto S . Contribution of the activation of satellite glia in sensory ganglia to pathological pain. Neurosci Biobehav Rev. 2009; 33(6):784-92. DOI: 10.1016/j.neubiorev.2008.12.005. View

Sasaki Y, Hoshi M, Akazawa C, Nakamura Y, Tsuzuki H, Inoue K . Selective expression of Gi/o-coupled ATP receptor P2Y12 in microglia in rat brain. Glia. 2003; 44(3):242-50. DOI: 10.1002/glia.10293. View

Milligan E, Watkins L . Pathological and protective roles of glia in chronic pain. Nat Rev Neurosci. 2008; 10(1):23-36. PMC: 2752436. DOI: 10.1038/nrn2533. View

Inoue K . Purinergic systems in microglia. Cell Mol Life Sci. 2008; 65(19):3074-80. PMC: 11131657. DOI: 10.1007/s00018-008-8210-3. View

Ren K, Dubner R . Neuron-glia crosstalk gets serious: role in pain hypersensitivity. Curr Opin Anaesthesiol. 2008; 21(5):570-9. PMC: 2735048. DOI: 10.1097/ACO.0b013e32830edbdf. View

10.

Shibasaki M, Sasaki M, Miura M, Mizukoshi K, Ueno H, Hashimoto S . Induction of high mobility group box-1 in dorsal root ganglion contributes to pain hypersensitivity after peripheral nerve injury. Pain. 2010; 149(3):514-521. DOI: 10.1016/j.pain.2010.03.023. View

11.

Jarvis M . The neural-glial purinergic receptor ensemble in chronic pain states. Trends Neurosci. 2009; 33(1):48-57. DOI: 10.1016/j.tins.2009.10.003. View

12.

Hernstadt H, Wang S, Lim G, Mao J . Spinal translocator protein (TSPO) modulates pain behavior in rats with CFA-induced monoarthritis. Brain Res. 2009; 1286:42-52. PMC: 2749299. DOI: 10.1016/j.brainres.2009.06.043. View

13.

Takeda M, Tanimoto T, Kadoi J, Nasu M, Takahashi M, Kitagawa J . Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation. Pain. 2006; 129(1-2):155-66. DOI: 10.1016/j.pain.2006.10.007. View

14.

Pannese E . The structure of the perineuronal sheath of satellite glial cells (SGCs) in sensory ganglia. Neuron Glia Biol. 2010; 6(1):3-10. DOI: 10.1017/S1740925X10000037. View

15.

Morin N, Owolabi S, Harty M, Papa E, Tracy Jr T, Shaw S . Neutrophils invade lumbar dorsal root ganglia after chronic constriction injury of the sciatic nerve. J Neuroimmunol. 2007; 184(1-2):164-71. DOI: 10.1016/j.jneuroim.2006.12.009. View

16.

Burnstock G . Purinergic receptors and pain. Curr Pharm Des. 2009; 15(15):1717-35. DOI: 10.2174/138161209788186335. View

17.

Zhuang Z, Kawasaki Y, Tan P, Wen Y, Huang J, Ji R . Role of the CX3CR1/p38 MAPK pathway in spinal microglia for the development of neuropathic pain following nerve injury-induced cleavage of fractalkine. Brain Behav Immun. 2006; 21(5):642-51. PMC: 2084372. DOI: 10.1016/j.bbi.2006.11.003. View

18.

Ballegaard V, Thede-Schmidt-Hansen P, Svensson P, Jensen R . Are headache and temporomandibular disorders related? A blinded study. Cephalalgia. 2008; 28(8):832-41. DOI: 10.1111/j.1468-2982.2008.01597.x. View

19.

Garrett F, Durham P . Differential expression of connexins in trigeminal ganglion neurons and satellite glial cells in response to chronic or acute joint inflammation. Neuron Glia Biol. 2009; 4(4):295-306. PMC: 3138122. DOI: 10.1017/S1740925X09990093. View

20.

Mueller C, Conrad S, Schluesener H, Pietsch T, Schwab J . Spinal cord injury-induced expression of the antiangiogenic endostatin/collagen XVIII in areas of vascular remodelling. J Neurosurg Spine. 2007; 7(2):205-14. DOI: 10.3171/SPI-07/08/205. View