Temporomandibular Joint Inflammation In Rats Research Articles

An analysis of the relationship between dietary pattern changes and temporomandibular joint inflammation in diabetic rats.

The temporomandibular joint (TMJ) is the most commonly used joint in the human body. Recent studies have shown pathologic relationships between inflammation, diabetes, and musculoskeletal disorders (MSDs). Chewing disorder is a significant sign of dysfunction in the masticatory system. This study investigated dietary pattern changes in response to TMJ inflammation in diabetic rats. This experimental study was carried out on 30 male rats. The rats were fed concentrated 20-mg dietary tablets. Complete Freund's adjuvant (CFA) was used to induce TMJ inflammation and streptozotocin (STZ) was used to induce diabetes. The animals were randomly divided into three groups (n=10), including group I (CFA+STZ), group II (healthy rats+CFA), and group III (healthy rats, no injection). Parameters such as overall food intake, food intake duration, food intake frequency, and the interval between meals were recorded in a checklist and analyzed by Mann-Whitney and Kruskal-Wallis tests (P<0.05). The results showed no significant difference between groups in overall food intake and food intake frequency on days 0 and 1, but this difference was significant from day 2 to day 7. Regarding the time and end of food intake, there was a significant difference between the three groups from day 1 to day 7, but this difference was not significant on day zero. Dietary pattern changes were similar in the diabetic TMJ inflammation and TMJ inflammation groups. These changes can be used as a behavioral marker for TMJ inflammation in rats.

Connexin 43 contributes to temporomandibular joint inflammation induced-hypernociception via sodium channel 1.7 in trigeminal ganglion

We previously demonstrated that sodium channel 1.7 (Nav1.7) in trigeminal ganglion (TG) was a critical factor in temporomandibular joint (TMJ) inflammation-induced hypernociception, but the mechanism underlying inflammation-induced upregulation of Nav1.7 remained unclear. Glial-neuron interaction plays a critical role in pain process and connexin 43 (Cx43), a gap junction protein expressed in satellite glial cells (SGCs) has been shown to play an important role in several pain models. In the present study, we investigate the role of Cx43 in TMJ inflammation-induced hypernociception and its possible impact on neuronal Nav1.7. We induced TMJ inflammation in rats by injecting complete Freund’s adjuvant (CFA) into TMJ and observed a decrease in head withdraw threshold after 24 h. Electron microscopy showed morphological alterations of SGCs in TMJ-inflamed rats. The expression of Cx43, glial fibrillary acidic protein (GFAP), and Nav1.7 increased greatly compared with controls. In addition, pretreatment with Cx43 blockers in TMJ-inflamed rats could alleviate mechanical hypernociception, inhibit SGCs activation and IL-1βrelease, and thus block the upregulation of Nav1.7. These findings indicate that the propagation of SGCs activation via Cx43 plays a critical role in Nav1.7-involved mechanical hypernociception induced by TMJ inflammation.

Estradiol-potentiated cadherin-11 in synovial membrane involves in temporomandibular joint inflammation in rats

Estrogen is involved in inflammation/pain of temporomandibular joint (TMJ), but the underlying mechanisms are largely unknown. Cadherin-11 plays an essential role in synovial inflammation. This study examined whether estrogen could potentiate cadherin-11 in synoviocytes and contribute to TMJ inflammatory pain. Female rats were ovariectomized, treated with increasing doses of 17β-estradiol for 10 days, and injected intra-articularly with complete Freund’s adjuvant to induce TMJ inflammation. The expression of cadherin-11 in synovial membrane was evaluated. TMJ pain was blocked with intra-articular injection of anti-cadherin-11 antibody and evaluated by head withdrawal threshold. Primary TMJ synoviocytes were treated with estradiol and tumor necrosis factor (TNF)-α or blocked with anti-cadherin-11 antibody to assess the expression of cadherin-11, interleukin (IL)-6, cyclooxygenase 2 (COX-2), and inducible nitric oxide synthase (iNOS). We observed that estradiol potentiated the inflammation-induced expression of cadherin-11 in the synoviocytes of synovial membrane from inflamed TMJ. Estradiol induced cadherin-11 expression in a dose- and time-dependent manner in primary synoviocytes and further potentiated the induction of cadherin-11 by TNF-α in synoviocytes. Furthermore, an estrogen receptor antagonist or a NF-κB inhibitor partially blocked the effects of estradiol on cadherin-11 induction in the synovial membrane. Blocking cadherin-11 partially reversed the TMJ inflammatory pain and estradiol-potentiated proliferation of synovial lining cells accompanied with iNOS expression. In addition, blocking cadherin-11 reversed TNF-α-induced and estradiol-potentiated transcription of IL-6, COX-2, and iNOS in primary synoviocytes. These results suggest that estrogen aggravated TMJ inflammatory pain partially through cadherin-11-mediated release of proinflammatory cytokines and enzymes in the synoviocytes.

Modulation of paratrigeminal nociceptive neurons following temporomandibular joint inflammation in rats

To evaluate the involvement of paratrigeminal nucleus (Pa5) nociceptive neurons in temporomandibular joint (TMJ) inflammation-induced pain and its autonomic correlates, we conducted behavioral, single unit recording and Fos immunohistochemical studies in anesthetized rats. Nocifensive behaviors to mechanical, heat or cold stimulation of the lateral face over the TMJ region were significantly enhanced in the TMJ-inflamed rats for 10–14 days after injection of complete Freund's adjuvant (CFA) into the TMJ and gradually decreased at the end of the 14-day observation period. Lowering of the nocifensive threshold in TMJ-inflamed rats lasted longer in vagus nerve-transected rats than vagus nerve-intact rats. A large number of Fos-like immunoreactive (LI) cells were observed in the Pa5, and half of them were retrogradely labeled with Fluorogold (FG) injected into the parabrachial nucleus. Background activity of Pa5 wide dynamic range and nociceptive specific neurons was significantly higher in the TMJ-inflamed rats when compared with controls. Responses to mechanical stimuli were significantly higher in NS neurons in the TMJ-inflamed rats. All thermal responsive Pa5 neurons were exclusively sensitive to cold and the response to cold was significantly higher in the TMJ-inflamed rats compared with control rats. Vagus nerve stimulation significantly decreased responses to mechanical and cold stimuli as well as the background activity in TMJ-treated rats but not in TMJ-untreated rats. The present findings suggest that populations of Pa5 neurons are nociceptive and involved in TMJ inflammation-induced pain as well as in autonomic processes related to TMJ pain.

Contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus produced by acute injury to the masseter muscle during persistent temporomandibular joint inflammation in rats

We investigated the contribution of peripheral 5-HT2A or 5-HT3 receptors to Fos expression in the trigeminal spinal nucleus (VSP) following acute masseter muscle injury in male rats with or without temporomandibular joint (TMJ) inflammation persisting for 7 days. TMJ inflammation was evoked by an injection of complete Freund’s adjuvant (CFA). Two hours after formalin injection into the masseter muscle produced Fos-like immunoreactivity (Fos-LI) in several regions of the VSP and upper cervical spinal cord (C2), such as ventrolateral (vl) area of the trigeminal subnucleus caudalis (Vc)/subnucleus interpolaris (Vi) transition (vl-Vi/Vc), paratrigeminal nucleus (dPa5), middle portion of the Vc (mid-Vc) and Vc/C2 transition (Vc/C2) regions in both groups. Significant increases in the number of Fos-LI were observed in these areas in CFA group compared with non-CFA group. TMJ inflammation alone did not induce a significant level of Fos-LI in the VSP. In order to assess the effect of antagonizing 5-HT2A or 5-HT3 receptors on formalin-induced Fos-LI, rats were pre-treated with local (masseter muscle) administration of ketanserin or tropisetron (0.01, 0.1 mg/rat) 20 min prior to formalin injection. In CFA group, these antagonists given locally reduced the Fos-LI response in the laminae I–II at the mid-Vc and Vc/C2 regions. These antagonists reduced the Fos-LI response in the dPa5, but not in the vl-Vi/Vc region. The Fos-LI response was not affected by i.v. administration of ketanserin (0.01, 0.1 mg/rat) or tropisetron (0.01 mg/rat). In non-CFA group, these antagonists given locally did not reduce the Fos-LI response. These results suggest that peripheral 5-HT2A and 5-HT3 receptors contribute to nociceptive processing in the masseter muscle in TMJ inflammatory conditions.

Activation of NK1 receptor of trigeminal root ganglion via substance P paracrine mechanism contributes to the mechanical allodynia in the temporomandibular joint inflammation in rats

Activation of NK1 receptor of trigeminal root ganglion via substance P paracrine mechanism contributes to the mechanical allodynia in the temporomandibular joint inflammation in rats

Activation of NK1 receptor of trigeminal root ganglion via substance P paracrine mechanism contributes to the mechanical allodynia in the temporomandibular joint inflammation in rats

The aim of this study was to investigate whether under in vivo conditions, temporomandibular joint (TMJ) inflammation alters the excitability of Aβ-trigeminal root ganglion (TRG) neuronal activity innervating the facial skin by using extracellular electrophysiological recording with multibarrel-electrodes. Complete Freund's adjuvant (CFA) was injected into the rat TMJ. Threshold for escape from mechanical stimulation applied to the whisker pad area in inflamed rats (2 days) was significantly lower than that in control rats. A total of 36 Aβ-TRG neurons responding to electrical stimulation of the whisker pad was recorded in pentobarbital-anesthetized rats. The number of Aβ-TRG neurons with spontaneous firings and their firing rate in TMJ inflamed rats were significantly larger than those in control rats. The firing rates of their spontaneous activity in the Aβ-TRG neurons were current-dependently decreased by local iontophoretic application of an NK1 receptor antagonist (L-703,606) in inflamed, but not non-inflamed rats. Their spontaneous activities were current-dependently increased by local iontophoretic application of substance P (SP) in control and inflamed rats. The mechanical response threshold of Aβ-TRG neurons in inflamed rats was significantly lower than that in control rats. The mechanical response threshold in inflamed rats after iontophoretic application of L-703,606 was not different from that in control rats. These results suggest that TMJ inflammation modulate the excitability of Aβ-TRG neurons innervating the facial skin via paracrine mechanism due to SP released from TRG neuronal cell body. Such a SP release may play an important role in determining the trigeminal inflammatory allodynia concerning the temporomandibular disorder.

A model for experimental induction of acute temporomandibular joint inflammation in rats: Effects of substance P(SP) on neuropeptide-like immunoreactivity

This is a study of neurokinin A (NKA)-, calcitonin gene-related peptide (CGRP)- and neuropeptide Y (NPY)-like immunoreactivity(-LI) in the cerebrospinal fluid (CSF), plasma and perfusates (PF) from the temporomandibular joints (TMJs) of the rat during acute inflammation. Substance P (10 −5 M, 0.01 ml) was injected into the right TMJ of the rat. The TMJs of the control rats, were injected with 0.01 ml saline. CSF, plasma and PF from TMJs were taken at 2, 6 and 24 hrs following injection. The neuropeptide-LI level was analysed by specific radioimmunoassays and compared with control values. Unilateral injection of SP into the rat TMJ resulted in a general increase in the concentration of NKA-, CGRP- and NPY-LI in the TMJ PF at 2, 6 and 24 hrs following injection. In the CSF NKA- and CGRP-LI was increased leaving the NPY-LI unaffected. In general no changes in peptide concentrations were seen in plasma. The results indicate that SP directly or indirectly induces a local release of peptides through an action at sensory and sympathetic neurons.