Temporomandibular Joint Injection Research Articles

Surgical incision can alter capsaicin-induced central sensitization in rat brainstem nociceptive neurons

Surgical trauma can affect spinal neuronal excitability, but there have been no studies of the effects of surgical cutaneous injury on central nociceptive processing of deep afferent inputs evoked by noxious stimuli such as capsaicin. Thus our aim was to test the effect of surgical cutaneous incision in influencing central sensitization induced by capsaicin injection into the temporomandibular joint (TMJ). The activity of single nociceptive neurons activated by noxious mechanical stimulation of the TMJ was recorded in the trigeminal subnucleus caudalis/upper cervical cord of halothane-anesthetized rats. The cutaneous mechanoreceptive field (RF), cutaneous mechanical activation threshold (MAT) and TMJ MAT of neurons before and after both surgical cutaneous incision alone and capsaicin injection were compared with results of incision and lidocaine pretreatment of the facial skin overlying the TMJ and capsaicin injection into the TMJ. Incision itself induced a barrage of neuronal spikes and excitability increases reflecting central sensitization (cutaneous RF expansion, cutaneous MAT reduction) in most neurons tested whereas lidocaine pretreatment significantly attenuated the barrage and central sensitization. Capsaicin injection into the TMJ induced cutaneous RF expansion, cutaneous MAT reduction and TMJ MAT reduction following lidocaine pretreatment of the cutaneous incision site whereas capsaicin injection following incision alone not only failed to induce further central sensitization but also decreased the existing incision-induced central sensitization (no cutaneous RF expansion, increased cutaneous MAT and TMJ MAT) in most neurons tested. These findings suggest that central sensitization induced by capsaicin alone or by cutaneous incision alone can readily occur in TMJ-responsive nociceptive neurons and that following incision-induced excitability increases, capsaicin may result in a temporary suppression of nociceptive neuronal changes reflecting central sensitization.

Injection of sodium hyaluronate compared with a corticosteroid in the treatment of patients with temporomandibular joint osteoarthritis: clinical effects and computed tomography evaluation of osseous changes

AbstractAim: We compared the osseous changes in the temporomandibular joint (TMJ), assessed on computed tomography (CT) examinations, before and after two intra‐articular TMJ injections of sodium hyaluronate or corticosteroid, in patients with osteoarthritis of the TMJ and related these to the clinical findings of pain, function and complications.Material and methods: Forty patients were randomly allocated into two groups for two intra‐articular injections with the two drugs. The effect of treatment was evaluated before and 6 months after the injections. Bilateral TMJ examinations with high resolution CT were obtained in 36 patients before and 6 months after treatment. Treated and contralateral TMJs were evaluated for the presence of osteoarthritic osseous abnormalities by two reviewers independently.Results: Injection with sodium hyaluronate was significantly more effective in decreasing pain intensity than corticosteroid. Progression, regression and no change of osseous abnormalities were demonstrated in 14, 10 and 12 TMJs, respectively, 6 months after treatment. Decreased pain intensity and increased vertical mandibular opening were observed in the majority of patients where progression of osseous changes was observed on CT.Conclusions: Injections in the TMJ with sodium hyaluronate or corticosteroid may reduce pain and improve function in patients with osteoarthritis. Progression, regression and no changes were observed in treated as well as untreated TMJs. Radiological evaluation of progression of osteoarthritis does not always reflect the clinical signs and symptoms.

Injection of sodium hyaluronate compared to a corticosteroid in the treatment of patients with temporomandibular joint osteoarthritis: a CT evaluation

Osseous changes in the temporomandibular joint (TMJ) were evaluated using computed tomography (CT) examinations before and after TMJ injections of sodium hyaluronate or a corticosteroid in patients with osteoarthritis (OA). Forty patients were randomly allocated into 2 groups for 2 intra-articular injections with either sodium hyaluronate or a corticosteroid. Bilateral TMJ examinations with high resolution CT were obtained in 36 patients before and 6 months after treatment. Treated and contralateral TMJs were evaluated for the presence of osteoarthritic osseous abnormalities by 2 reviewers independently. Progression, regression, and no changes of osseous abnormalities were demonstrated in 13, 9, and 14 TMJs, respectively, 6 months after treatment. There was no significant difference between the groups. Progression/regression and no changes of osteoarthritic abnormalities were observed on CT examinations in both the treated and the contralateral TMJs after treatment with intra-articular injection with sodium hyaluronate or corticosteroid.

The Analgesic Efficacy and Safety of Intra-Articular Morphine and Mepivicaine Following Temporomandibular Joint Arthroplasty

This study was designed to evaluate the efficacy and safety of intra-articular morphine, mepivacaine, or a combination of both in the management of temporomandibular joint (TMJ) pain in a 24-hour period after arthroplasty. This was a randomized, double-blind, prospective, parallel, placebo-controlled, single-injection study of 35 patients who underwent TMJ arthroplasty. Patients were randomized into 4 groups. Group M (morphine) received 1 mg of morphine sulfate in 1 mL of saline; group MEP (mepivicaine) received 30 mg of mepivacaine hydrochloride in 1 mL of saline; group M/MEP received 30 mg of mepivacaine hydrochloride and 1 mg of morphine in 1 mL of saline; and group C (saline control) received 1 mL of saline. Patients received a single dose of study medication when their postoperative pain reached a moderate or severe intensity and was 50 mm or greater on a 100-mm pain scale. Analgesic efficacy measures included the time to meaningful pain relief measured using a stop watch and time to rescue medication. Pain relief and pain intensity ratings were recorded at the time to relief and time to rescue medication. A global evaluation for the effectiveness of the medications was recorded within 24 hours after dosing. Adverse events were recorded and categorized by system effect. MEP and M/MEP were significantly more effective than placebo for all the analgesic measures. Morphine alone provided only mild analgesia and did not differ from placebo in the primary efficacy measures. The average overall pain relief was substantially better for MEP than M and M/MEP (P = .03). In patients receiving MEP, the mean time to pain relief was 2.9 minutes and the mean analgesic duration was 9.7 hours (586 minutes); 3 patients required no rescue medication in the 24 hour postdosing period. In patients receiving M/MEP, the mean time to analgesia was 7.6 minutes and the duration of analgesia was 2.7 hours (175 minutes). The average time to onset and duration of analgesia in the MEP and M/MEP groups was statistically significantly better (P < .001) then in the M alone group (17.7 minutes, 0.43 hours, respectively) and the placebo C group (16.1 minutes, 0.17 hours, respectively). At the end of the study, 80% of the patients given MEP rated the medication as a very good or excellent pain reliever, whereas only 40% of patients given M/MEP, 10% of patients given M, and no patients given placebo gave these same ratings. No serious adverse events occurred in this study. Gastrointestinal adverse events were the most common side effect noted in the MEP and M/MEP groups but were mild in intensity and reversed without treatment. All intra-articular TMJ injections of active substances provided better analgesia than placebo. Morphine alone provided only mild and short-acting analgesia. The local anesthetic, mepivacaine, given alone was safe, provided the quickest, longest acting and most effective analgesia. This proof of concept study suggests that local anesthetics are superior analgesics when given intra-articularly for postoperative TMJ surgery pain and should be investigated for dose response and multiple or continuous infusion effectiveness.

The Protective Role of Testosterone in the Development of Temporomandibular Joint Pain

The lower prevalence of many pain conditions, including temporomandibular dysfunctions, in men than in women has not as yet been clarified. The aim of this study was to investigate the effect of testosterone on the risk of development of temporomandibular joint (TMJ) pain and on acute persistent TMJ pain. The TMJ formalin test was used as an experimental assay in the rat. Intra-TMJ 0.5% formalin induced a significant nociceptive behavior in naive female rats and gonadectomized male rats but not in naive male rats, suggesting that naive male rats have a lower risk for development of TMJ pain. The finding that the serum level of testosterone but not of estrogen and progesterone significantly decreased in gonadectomized male rats suggests that testosterone is the hormone underlying the decreased naive male rat's risk for development of TMJ pain. The magnitude of the nociceptive behaviors induced by intra-TMJ 1.5% formalin was similar in gonadectomized and naive male rats. Therefore, in contrast to the protective role of testosterone in TMJ pain development, testosterone, at physiological serum levels, does not appear to modulate acute persistent TMJ pain induced by the TMJ injection of 1.5% formalin. At a supraphysiological serum level, however, testosterone significantly attenuated 1.5% formalin-induced nociception in male rats but not in female rats. This antinociceptive effect was not mediated by estrogen derived from testosterone aromatization, because estrogen administration did not affect 1.5% formalin-induced TMJ nociception in gonadectomized male rats. The present findings not only help to explain the lower prevalence of TMJ pain in males versus females but also show that testosterone reduces TMJ pain at supraphysiological serum levels.

Peripheral Sympathetic Component of the Temporomandibular Joint Inflammatory Pain in Rats

The aim of this study was to further validate our carrageenan-induced temporomandibular joint (TMJ) inflammatory hyperalgesia model in rats by showing that administration of indomethacin before the initiation of inflammation would diminish the TMJ hyperalgesia. Using this model, we investigated whether norepinephrine and local β-adrenoceptors contribute to the development of inflammatory TMJ hyperalgesia. Carrageenan-induced TMJ hyperalgesia was assessed by measuring the behavioral nociceptive responses, such as rubbing the orofacial region and flinching the head, induced by the injection of a low dose of 5-hydroxytryptamine into the TMJ sensitized 1 h before by a TMJ injection of carrageenan. Blockade of prostaglandin synthesis by indomethacin prior to initiation of inflammation by carrageenan significantly attenuated the TMJ hyperalgesia. The guanethidine depletion of norepinephrine or the blockade of β 2 but not the blockade of the β 1 - adrenoceptor by the selective adrenoceptor antagonists ICI 118.55 and atenolol, respectively, significantly reduced carrageenan-induced TMJ hyperalgesia. In the present study, we further validated our carrageenan-induced TMJ hyperalgesia model to study the mechanisms involved in inflammatory TMJ hyperalgesia and to test the analgesic effect of different types of peripheral analgesics. We also demonstrated that norepinephrine released at the site of injury contributes to the development of the inflammatory TMJ hyperalgesia by the activation of β 2 -adrenoceptors. Perspective The findings that local sympathomimetic amines contribute to the inflammatory TMJ hyperalgesia by activating β 2-adrenoceptors may be relevant to clinical TMJ inflammatory pain states less sensitive to nonsteroidal anti-inflammatory drugs.

Utility of corticosteroid injection for temporomandibular arthritis in children with juvenile idiopathic arthritis

To assess the effects of computed tomography (CT)-guided injection of corticosteroid into the temporomandibular joint (TMJ) in children with juvenile idiopathic arthritis (JIA) and clinical and magnetic resonance imaging (MRI) evidence of TMJ inflammation. Twenty-three children ages 4-16 years with JIA and MRI evidence of TMJ inflammation received CT-guided TMJ injections of corticosteroid (triamcinolone acetonide [n = 16] or triamcinolone hexacetonide [n = 7]). Jaw pain or dysfunction and maximal incisal opening (MIO) distance were assessed before and after injection. Fourteen patients had followup MRI studies of the TMJ 6-12 months after injection. Of the 13 patients with symptoms of jaw pain prior to corticosteroid treatment, 10 (77%) had complete resolution of pain (P < 0.05). Prior to corticosteroid injection, MIO in all 23 patients was below age-matched normal values. After injection, the MIO was improved by at least 0.5 cm in 10 patients (43%) (P = 0.0017). Patients under 6 years of age at the time of injection showed the best response, with a postinjection MIO similar to that in age-matched controls (P = 0.2267). There was involvement of 23 TMJs in the 14 patients who had followup MRI studies; resolution of effusions was observed in 11 (48%) of the TMJs. Other than short-term facial swelling in 2 patients, there were no side effects. The majority of children with symptomatic TMJ arthritis improved after intraarticular corticosteroid injection. Approximately half the patients experienced significant improvement in MIO and TMJ effusion. These data suggest that corticosteroid injection may be a useful procedure for the prevention and treatment of morbidities associated with TMJ arthritis in JIA.

Estrogenic effect on swelling and monocytic receptor expression in an arthritic temporomandibular joint model

Clinical presentation of temporomandibular joint (TMJ) disorders are more common in women and changes in the female hormone estrogen affect the level of swelling, pro-inflammatory cytokine release and pain in animal models of TMJ arthritis. Estrogen also modulates the expression of the CD16 receptor in vitro. This alters pro-inflammatory cytokine release in monocytes/macrophages when auto-antigens and arthritic factors bind the CD16 receptor. This study investigated the effects of various levels of estrogen on the intensity of inflammation and CD16 expression in a TMJ arthritic animal model. The experiments included rats that were intact or ovariectomized (OVX), eliminating the major source of estrogen output. A portion of the OVX animals had estrogen replaced with 17-β estradiol (E2) using Alzet ® pumps. In OVX animals E2 levels were administered for 10 days to create an artificial estrus cycle or to simulate pregnancy. Following E2 treatment the rats were given an intra-articular TMJ injection of saline or complete Freund's adjuvant (CFA). CFA injection significantly increased TMJ swelling, stress induced chromodacryorrhea and attenuated food intake, thus indicating the adjuvant induced TMJ pain/inflammation. Removing endogenous E2 through OVX reduced CFA induced TMJ inflammation, whereas CFA increased the number of TMJ monocytes expressing the CD14 receptor equally in all groups irrespective of plasma E2 levels. Paradoxically, higher levels of E2 reduced the number of TNF-α positive, CD16+ and double labeled CD14+/CD16+ cells. The findings indicate that reduced plasma E2 levels attenuated CFA induced TMJ inflammation, whereas increasing E2 levels enhanced TMJ swelling in a dose dependent manner. Estrogenic group differences in CFA induced swelling were independent of TMJ CD14+, CD14+/CD16+ or CD16+ cell numbers suggesting E2 action on the CFA immune response primarily excluded CD16 receptor action.

Specificity of meal pattern analysis as an animal model of determining temporomandibular joint inflammation/pain

Analyzing feeding behavior, and in particular meal duration, can be used as a biological marker for temporomandibular joint (TMJ) inflammation/pain. The present study determined the specificity of meal duration as a measure of TMJ inflammation/pain in a rodent model. The model was also used to test the efficacy of dexamethasone (DEX) as a treatment for TMJ inflammation/pain that was induced by TMJ injection of complete Freund's adjuvant (CFA). In the first study, anesthetized male Sprague–Dawley rats housed in computerized feeding modules received bilateral intra-articular knee injections of CFA or saline. The next day, CFA-injected rats had significant knee swelling and impaired mobility. Food intake in the CFA-injected group was reduced over the next two days and this was due to reduced meal number with no change in meal size. Notably, meal duration was normal in both the CFA and saline knee-injected groups. In the second study, male rats were assigned to one of four groups: Group 1, no CFA and no DEX treatment; Group 2, no CFA and treatment with DEX (0.4 mg/kg i.m. once daily); Group 3, bilateral TMJ CFA injection and no DEX treatment; and Group 4, bilateral TMJ CFA injection and treatment with DEX. CFA significantly increased TMJ swelling and stress-induced chromodacryorrhea in Group 3, but treatment with DEX attenuated these effects in Group 4. Compared to the controls, meal duration was significantly lengthened 24 and 48 h post-CFA injection in Group 3, whereas DEX treatment attenuated TMJ swelling, chromodacryorrhea and normalized meal duration. The data demonstrate that meal pattern analysis, and in particular meal duration, can be used as a non-invasive specific measure of TMJ inflammation/pain and can be used as a marker of DEX treatment efficacy.

Development of a behavioral model of TMJ pain in rats: the TMJ formalin test

Temporomandibular joint (TMJ) pain conditions are poorly understood. Since formalin is a noxious stimulus widely used in animal behavioral experiments for studying pain mechanisms, the aim of this study was to develop a behavioral model to study the TMJ pain conditions by characterizing the nociceptive behavioral responses induced by the injection of formalin into the TMJ region of rats. NaCl (0.9%) or different concentrations of formalin (0.5, 1.5, 2.5 or 5%) were administrated into the TMJ region. The formalin-induced behavioral responses characterized by moving the mandible, rubbing the orofacial region and flinching the head quickly were quantified for 45 min. The TMJ injection of formalin significantly increased the asymmetrical orofacial rubbing and head flinching behaviors, but not the movement of the mandible with concentrations of 1.5% and above ( P<0.05, Dunn's test) when compared with the NaCl (0.9%) injection. These responses were significantly reduced ( P<0.05, Mann–Whitney test) by the co-application of lidocaine N-ethyl bromide quaternary salt, QX-314 (2%), and by the administration of intraperitoneal morphine (4 mg/kg) 30 min prior to the TMJ formalin injection. This study demonstrates that the injection of formalin into the TMJ region of rats produces quantitative nociceptive behaviors constituting a novel behavioral model for TMJ pain.

Effects of inflammatory irritant application to the rat temporomandibular joint on jaw and neck muscle activity

An electromyographic (EMG) study was carried out in 40 anaesthetized rats to determine if the activity of jaw and neck muscles could be influenced by injection of the small-fibre excitant and inflammatory irritant mustard oil into the region of the temporomandibular joint (TMJ). Injection of a vehicle (mineral oil, 20 μl) did not produce any significant change in EMG activity. In contrast, injection of mustard oil (20 μl, 20%) evoked increases in EMG activity in the jaw muscles but not in the neck muscles. The increased EMG activity evoked by mustard oil was reflected in 1 or 2 phases of increased activity. The early EMG increase occurred soon after the mustard oil injection (mean latency ± SD: 3.5 ± 2.3 sec), peaked within 1 min, and then subsided (mean duration: 7.5 ± 5.2 min). The later EMG increase occurred at 14.6 ± 10.0 min after the mustard oil injection and lasted 14.3 ± 12.3 min. These excitatory effects of mustard oil on the EMG activity of jaw muscles appear to have a reflex basis since they could be abolished by pre-administration of local anaesthetic into the TMJ region. These results document that TMJ injection of mustard oil results in a sustained and reversible activation of jaw muscles that may be related to the reported clinical occurrence of increased muscle activity associated with trauma to the TMJ.