scholarly journals Role of Macrophage-Mediated Toll-like receptor 4–Interleukin-1R Signaling in Ectopic Tongue Pain Associated With Tooth Pulp Inflammation

2020 ◽  
Author(s):  
Kohei Kanno ◽  
Kohei Shimizu ◽  
Masamichi Shinoda ◽  
Makoto Hayashi ◽  
Osamu Takeichi ◽  
...  
Keyword(s):  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Tooth Pulp ◽  
Transient Receptor Potential Vanilloid ◽  
Type I ◽  
Expression Levels ◽  
Withdrawal Threshold ◽  
Pulp Inflammation ◽  
Tlr4 Agonist ◽  
Transient Receptor

Abstract Background Ectopic orofacial pain is frequently caused by tooth pulp inflammation. However, the detailed mechanism underlying such pain remains poorly understood.Methods To better understand this phenomenon, ectopic pain mechanism was studied in a rat model of mandibular first molar tooth pulp exposure (M1-TPE).Results One day after M1-TPE, obvious pulpal inflammation was observed in M1 pulp. The head withdrawal threshold to mechanical and heat stimulation of the tongue was significantly reduced in M1-TPE rats on day 1 after TPE. In addition, the production of interleukin-1β (IL-1β) in activated macrophages and expression levels of Toll-like receptors (TLRs) and IL-1 type I receptor (IL-1RΙ) were significantly increased in the trigeminal ganglion (TG) neurons innervating the tongue following M1-TPE. Injection of the selective macrophage depletion compound liposomal clodronate Clophosome-A into the TG significantly suppressed tongue hypersensitivity; however, expression levels of TLR4 and IL-1RΙ in TG neurons innervating the tongue were not significantly altered. Injection of lipopolysaccharide from Rhodobacter sphaeroides, a TLR4 antagonist, into the TG following TPE significantly suppressed tongue hypersensitivity and reduced IL-1RΙ expression in TG neurons innervating the tongue. Moreover, an intra-TG injection of recombinant heat shock protein 70, a selective TLR4 agonist, significantly promoted the development of tongue-hypersensitivity and increased the production of IL-1RI in TG neurons innervating the tongue in naive rats. Furthermore, an intra-TG injection of recombinant IL-1β led to the development of tongue hypersensitivity in naive rats and enhanced the expression of transient receptor potential vanilloid 1 in the TG neurons innervating the tongue.Conclusions The present findings suggest that the neuron-macrophage interaction mediated by TLR4 and IL-1RI activation in TG neurons affects the pathogenesis of abnormal tongue pain following tooth pulp inflammation via TLR4-ILR and TRPV1 signaling in the TG.

scholarly journals Role of Transient Receptor Potential Vanilloid 1 in Electroacupuncture Analgesia on Chronic Inflammatory Pain in Mice

2017 ◽  
Vol 2017 ◽  
pp. 1-8 ◽  
Author(s):  
Jun Yang ◽  
Ching-Liang Hsieh ◽  
Yi-Wen Lin
Keyword(s):  
Inflammatory Pain ◽  
Transient Receptor Potential ◽  
Tissue Injury ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Expression Levels ◽  
Chronic Inflammatory Pain ◽  
Cytokines And Chemokines ◽  
Transient Receptor

Chronic inflammatory pain may result from peripheral tissue injury or inflammation, increasing the release of protons, histamines, adenosine triphosphate, and several proinflammatory cytokines and chemokines. Transient receptor potential vanilloid 1 (TRPV1) is known to be involved in acute to subacute neuropathic and inflammatory pain; however, its exact mechanisms in chronic inflammatory pain are not elucidated. Our results showed that EA significantly reduced chronic mechanical and thermal hyperalgesia in the chronic inflammatory pain model. Chronic mechanical and thermal hyperalgesia were also abolished in TRPV1−/− mice. TRPV1 increased in the dorsal root ganglion (DRG) and spinal cord (SC) at 3 weeks after CFA injection. The expression levels of downstream molecules such as pPKA, pPI3K, and pPKC increased, as did those of pERK, pp38, and pJNK. Transcription factors (pCREB and pNFκB) and nociceptive ion channels (Nav1.7 and Nav1.8) were involved in this process. Inflammatory mediators such as GFAP, S100B, and RAGE were also involved. The expression levels of these molecules were reduced in EA and TRPV1−/− mice but not in the sham EA group. Our data provided evidence to support the clinical use of EA for treating chronic inflammatory pain.

scholarly journals MZF1 in the Dorsal Root Ganglia Contributes to the Development and Maintenance of Neuropathic Pain via Regulation of TRPV1

2019 ◽  
Vol 2019 ◽  
pp. 1-13
Author(s):  
Fei Xing ◽  
Hanwen Gu ◽  
Qin Niu ◽  
Xiaochong Fan ◽  
Zhongyu Wang ◽  
...  
Keyword(s):  
Neuropathic Pain ◽  
Zinc Finger ◽  
Dorsal Root ◽  
Transient Receptor Potential ◽  
Thermal Hyperalgesia ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Withdrawal Threshold ◽  
Lumbar Level ◽  
Transient Receptor

Previous studies have demonstrated that myeloid zinc finger 1 (MZF1) in the dorsal root ganglion (DRG) participates in neuropathic pain induced by chronic-constriction injury (CCI) via regulation of voltage-gated K+ channels (Kv). Emerging evidence indicates that transient receptor potential vanilloid 1 (TRPV1) is involved in the development and maintenance of neuropathic pain. Although it is known that the transcription of TRPV1 is regulated by Kruppel-like zinc-finger transcription factor 7 (Klf7)—and that the structure of TRPV1 is similar to that of Kv—few studies have systematically investigated the relationship between MZF1 and TRPV1 in neuropathic pain. In the present study, we demonstrated that CCI induced an increase in MZF1 and TRPV1 in lumbar-level 4/5 (L4/5) DRGs at 3 days post-CCI and that this increase was persistent until at least 14 days post-CCI. DRG microinjection of rAAV5-MZF1 into the DRGs of naïve rats resulted in a decrease in paw-withdrawal threshold (PWT) and paw-withdrawal latency (PWL) compared with that of the rAAV5-EGFP group, which started at four weeks and lasted until at least eight weeks after microinjection. Additionally, prior microinjection of MZF1 siRNA clearly ameliorated CCI-induced reduction in PWT and PWL at 3 days post-CCI and lasted until at least 7 days post-CCI. Correspondingly, microinjection of MZF1 siRNA subsequent to CCI alleviated the established mechanical allodynia and thermal hyperalgesia induced by CCI, which occurred at 3 days postinjection and lasted until at least 10 days postinjection. Microinjection of rAAV5-MZF1 increased the expression of TRPV1 in DRGs. Microinjection of MZF1 siRNA diminished the CCI-induced increase of TRPV1, but not P2X7R, in DRGs. These findings suggest that MZF1 may contribute to neuropathic pain via regulation of TRPV1 expression in DRGs.

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