J Dent Anesth Pain Med.  2019 Apr;19(2):77-82. 10.17245/jdapm.2019.19.2.77.

Role of neuron and non-neuronal cell communication in persistent orofacial pain

• Iwata K
• Shinoda M

• KMID: 2444751
• DOI: http://doi.org/10.17245/jdapm.2019.19.2.77

Abstract

It is well known that trigeminal nerve injury causes hyperexcitability in trigeminal ganglion neurons, which become sensitized. Long after trigeminal nerve damage, trigeminal spinal subnucleus caudalis and upper cervical spinal cord (C1/C2) nociceptive neurons become hyperactive and are sensitized, resulting in persistent orofacial pain. Communication between neurons and non-neuronal cells is believed to be involved in these mechanisms. In this article, the authors highlight several lines of evidence that neuron-glial cell and neuron macrophage communication have essential roles in persistent orofacial pain mechanisms associated with trigeminal nerve injury and/or orofacial inflammation.

Keyword

Cell Communication; Orofacial Persistent Pain; Spinal Trigeminal Nucleus; Trigeminal Ganglion

MeSH Terms

Cell Communication*
Cervical Cord
Facial Pain*
Inflammation
Macrophages
Neurons*
Nociceptors
Trigeminal Ganglion
Trigeminal Nerve
Trigeminal Nerve Injuries
Trigeminal Nucleus, Spinal

Reference

1. Sessle BJ. The neurobiology of facial and dental pain: present knowledge, future directions. J Dent Res. 1987; 66:962–981.

2. Dubner R, Bennett GJ. Spinal and trigeminal mechanisms of nociception. Annu Rev Neurosci. 1983; 6:381–418.

3. Bereiter DA, Hirata H, Hu JW. Trigeminal subnucleus caudalis: beyond homologies with the spinal dorsal horn. Pain. 2000; 88:221–224.

4. Herculano-Houzel S. The glia/neuron ratio: how it varies uniformly across brain structures and species and what that means for brain physiology and evolution. Glia. 2014; 62:1377–1391.

5. Zhang ZJ, Jiang BC, Gao YJ. Chemokines in neuron-glial cell interaction and pathogenesis of neuropathic pain. Cell Mol Life Sci. 2017; 74:3275–3291.

6. Tsuboi Y, Takeda M, Tanimoto T, Ikeda M, Matsumoto S, Kitagawa J, et al. Alteration of the second branch of the trigeminal nerve activity following inferior alveolar nerve transection in rats. Pain. 2004; 111:323–334.

7. Batbold D, Shinoda M, Honda K, Furukawa A, Koizumi M, Akasaka R, et al. Macrophages in trigeminal ganglion contribute to ectopic mechanical hypersensitivity following inferior alveolar nerve injury in rats. J Neuroinflammation. 2017; 14:249.

8. Pannese E. The satellite cells of the sensory ganglia. Adv Anat Embryol Cell Biol. 1981; 65:1–111.

9. Li L, Zhou XF. Pericellular Griffonia simplicifolia I isolectin B4-binding ring structures in the dorsal root ganglia following peripheral nerve injury in rats. J Comp Neurol. 2001; 439:259–274.

10. Xie W, Strong JA, Meij JT, Zhang JM, Yu L. Neuropathic pain: early spontaneous afferent activity is the trigger. Pain. 2005; 116:243–256.

11. Xie W, Strong JA, Zhang JM. Early blockade of injured primary sensory afferents reduces glial cell activation in two rat neuropathic pain models. Neuroscience. 2009; 160:847–857.

12. Kushnir R, Cherkas PS, Hanani M. Peripheral inflammation upregulates P2X receptor expression in satellite glial cells of mouse trigeminal ganglia: a calcium imaging study. Neuropharmacology. 2011; 61:739–746.

13. Chessell IP, Hatcher JP, Bountra C, Michel AD, Hughes JP, Green P, et al. Disruption of the P2X7 purinoceptor gene abolishes chronic inflammatory and neuropathic pain. Pain. 2005; 114:386–396.

14. Gu Y, Chen Y, Zhang X, Li GW, Wang C, Huang LY. Neuronal soma-satellite glial cell interactions in sensory ganglia and the participation of purinergic receptors. Neuron Glia Biol. 2010; 6:53–62.

15. Chen Y, Zhang X, Wang C, Li G, Gu Y, Huang LY. Activation of P2X7 receptors in glial satellite cells reduces pain through downregulation of P2X3 receptors in nociceptive neurons. Proc Natl Acad Sci U S A. 2008; 105:16773–16778.

16. Ceruti S, Fumagalli M, Villa G, Verderio C, Abbracchio MP. Purinoceptor-mediated calcium signaling in primary neuron-glia trigeminal cultures. Cell Calcium. 2008; 43:576–590.

17. Xu JT, Xin WJ, Zang Y, Wu CY, Liu XG. The role of tumor necrosis factor-alpha in the neuropathic pain induced by Lumbar 5 ventral root transection in rat. Pain. 2006; 123:306–321.

18. Takeda M, Tanimoto T, Kadoi J, Nasu M, Takahashi M, Kitagawa J, et al. Enhanced excitability of nociceptive trigeminal ganglion neurons by satellite glial cytokine following peripheral inflammation. Pain. 2007; 129:155–166.

19. Takeda M, Takahashi M, Matsumoto S. Contribution of activated interleukin receptors in trigeminal ganglion neurons to hyperalgesia via satellite glial interleukin-1beta paracrine mechanism. Brain Behav Immun. 2008; 22:1016–1023.

20. Hensellek S, Brell P, Schaible HG, Brauer R, Segond von Banchet G. The cytokine TNFalpha increases the proportion of DRG neurones expressing the TRPV1 receptor via the TNFR1 receptor and ERK activation. Mol Cell Neurosci. 2007; 36:381–391.

21. Chen X, Pang RP, Shen KF, Zimmermann M, Xin WJ, Li YY, et al. TNF-alpha enhances the currents of voltage gated sodium channels in uninjured dorsal root ganglion neurons following motor nerve injury. Exp Neurol. 2011; 227:279–286.

22. He XH, Zang Y, Chen X, Pang RP, Xu JT, Zhou X, et al. TNF-alpha contributes to up-regulation of Nav1.3 and Nav1.8 in DRG neurons following motor fiber injury. Pain. 2010; 151:266–279.

23. Jin X, Gereau RWt. Acute p38-mediated modulation of tetrodotoxin-resistant sodium channels in mouse sensory neurons by tumor necrosis factor-alpha. J Neurosci. 2006; 26:246–255.

24. Donegan M, Kernisant M, Cua C, Jasmin L, Ohara PT. Satellite glial cell proliferation in the trigeminal ganglia after chronic constriction injury of the infraorbital nerve. Glia. 2013; 61:2000–2008.

25. Komori T, Morikawa Y, Inada T, Hisaoka T, Senba E. Site-specific subtypes of macrophages recruited after peripheral nerve injury. Neuroreport. 2011; 22:911–917.

26. Lu X, Richardson PM. Responses of macrophages in rat dorsal root ganglia following peripheral nerve injury. J Neurocytol. 1993; 22:334–341.

27. Harvey LD, Yin Y, Attarwala IY, Begum G, Deng J, Yan HQ, et al. Administration of DHA Reduces Endoplasmic Reticulum Stress-Associated Inflammation and Alters Microglial or Macrophage Activation in Traumatic Brain Injury. ASN Neuro. 2015; 7:1759091415618969.

28. Abbadie C, Lindia JA, Cumiskey AM, Peterson LB, Mudgett JS, Bayne EK, et al. Impaired neuropathic pain responses in mice lacking the chemokine receptor CCR2. Proc Natl Acad Sci U S A. 2003; 100:7947–7952.

29. Kwon MJ, Shin HY, Cui Y, Kim H, Thi AH, Choi JY, et al. CCL2 Mediates Neuron-Macrophage Interactions to Drive Proregenerative Macrophage Activation Following Preconditioning Injury. J Neurosci. 2015; 35:15934–15947.

30. Kim D, You B, Lim H, Lee SJ. Toll-like receptor 2 contributes to chemokine gene expression and macrophage infiltration in the dorsal root ganglia after peripheral nerve injury. Mol Pain. 2011; 7:74.

31. Raghavendra V, Tanga F, Rutkowski MD, DeLeo JA. Anti-hyperalgesic and morphine-sparing actions of propentofylline following peripheral nerve injury in rats: mechanistic implications of spinal glia and proinflammatory cytokines. Pain. 2003; 104:655–664.

32. Wagner R, Myers RR. Endoneurial injection of TNF-alpha produces neuropathic pain behaviors. Neuroreport. 1996; 7:2897–2901.

33. Wang CL, Lu CY, Pi CC, Zhuang YJ, Chu CL, Liu WH, et al. Extracellular polysaccharides produced by Ganoderma formosanum stimulate macrophage activation via multiple pattern-recognition receptors. BMC Complement Altern Med. 2012; 12:119.

34. Fu C, Yin Z, Yu D, Yang Z. Substance P and calcitonin gene-related peptide expression in dorsal root ganglia in sciatic nerve injury rats. Neural Regen Res. 2013; 8:3124–3130.

35. Sun J, Ramnath RD, Zhi L, Tamizhselvi R, Bhatia M. Substance P enhances NF-kappaB transactivation and chemokine response in murine macrophages via ERK1/2 and p38 MAPK signaling pathways. Am J Physiol Cell Physiol. 2008; 294:C1586–C1596.

36. Matsumoto K, Nakajima T, Sakai H, Kato S, Sagara A, Arakawa K, et al. Increased expression of 5-HT3 and NK 1 receptors in 5-fluorouracil-induced mucositis in mouse jejunum. Dig Dis Sci. 2013; 58:3440–3451.

37. Bardelli C, Gunella G, Varsaldi F, Balbo P, Del Boca E, Bernardone IS, et al. Expression of functional NK1 receptors in human alveolar macrophages: superoxide anion production, cytokine release and involvement of NF-kappaB pathway. Br J Pharmacol. 2005; 145:385–396.

38. Noma N, Tsuboi Y, Kondo M, Matsumoto M, Sessle BJ, Kitagawa J, et al. Organization of pERK-immunoreactive cells in trigeminal spinal nucleus caudalis and upper cervical cord following capsaicin injection into oral and craniofacial regions in rats. J Comp Neurol. 2008; 507:1428–1440.

39. Iwata K, Imai T, Tsuboi Y, Tashiro A, Ogawa A, Morimoto T, et al. Alteration of medullary dorsal horn neuronal activity following inferior alveolar nerve transection in rats. J Neurophysiol. 2001; 86:2868–2877.

40. Ji RR, Baba H, Brenner GJ, Woolf CJ. Nociceptive-specific activation of ERK in spinal neurons contributes to pain hypersensitivity. Nat Neurosci. 1999; 2:1114–1119.

41. Suzuki I, Tsuboi Y, Shinoda M, Shibuta K, Honda K, Katagiri A, et al. Involvement of ERK phosphorylation of trigeminal spinal subnucleus caudalis neurons in thermal hypersensitivity in rats with infraorbital nerve injury. PLoS One. 2013; 8:e57278.

42. Okada-Ogawa A, Suzuki I, Sessle BJ, Chiang CY, Salter MW, Dostrovsky JO, et al. Astroglia in medullary dorsal horn (trigeminal spinal subnucleus caudalis) are involved in trigeminal neuropathic pain mechanisms. J Neurosci. 2009; 29:11161–11171.

43. Shibuta K, Suzuki I, Shinoda M, Tsuboi Y, Honda K, Shimizu N, et al. Organization of hyperactive microglial cells in trigeminal spinal subnucleus caudalis and upper cervical spinal cord associated with orofacial neuropathic pain. Brain Res. 2012; 1451:74–86.

44. Chiang CY, Dostrovsky JO, Iwata K, Sessle BJ. Role of glia in orofacial pain. Neuroscientist. 2011; 17:303–320.

45. Inoue K. A state-of-the-art perspective on microgliopathic pain. Open Biol. 2018; 8:180154.

46. Rothhammer V, Borucki DM, Tjon EC, Takenaka MC, Chao CC, Ardura-Fabregat A, et al. Microglial control of astrocytes in response to microbial metabolites. Nature. 2018; 557:724–728.