Blockade of Piezo2 Pathway Attenuates Inflammatory and Neuropathic Pain in the Orofacial Area.

Although previous studies suggest that Piezo2 regulates chronic pain in the orofacial area, few studies have reported the direct evidence of Piezo2's involvement in inflammatory and neuropathic pain in the orofacial region. In this study, we used male Sprague Dawley rats to investigate the role of the Piezo2 pathway in the development of inflammatory and neuropathic pain. The present study used interleukin (IL)-1ß-induced pronociception as an inflammatory pain model. Subcutaneous injection of IL-1ß produced significant mechanical allodynia and thermal hyperalgesia. Subcutaneous injection of a Piezo2 inhibitor significantly blocked mechanical allodynia and thermal hyperalgesia induced by subcutaneously injected IL-1ß. Furthermore, the present study also used a neuropathic pain model caused by the misplacement of a dental implant, leading to notable mechanical allodynia as a consequence of inferior alveolar nerve injury. Western blot analysis revealed increased levels of Piezo2 in the trigeminal ganglion and the trigeminal subnucleus caudalis after inferior alveolar nerve injury. Furthermore, subcutaneous and intracisternal injections of a Piezo2 inhibitor blocked neuropathic mechanical allodynia. These results suggest that the Piezo2 pathway plays a critical role in the development of inflammatory and neuropathic pain in the orofacial area. Therefore, blocking the Piezo2 pathway could be the foundation for developing new therapeutic strategies to treat orofacial pain conditions.

The preliminary study of the effects of individual musculoskeletally stable position in the treatment of temporomandibular disorders.

BACKGROUND: Temporomandibular Disorders (TMD) is the dysfunction of group of muscles and bones in the joint area, the main symptoms of TMD are the pain of the chewing muscles and (or) the temporomandibular joints, mandibular movement disorders and joint noise. This study was designed to explore the therapeutic effects following Individual Musculoskeletally Stable (IMS) position stabilization splint therapy for TMD patients using Fricton index, cone beam computed tomography (CBCT) and surface-Electromyogram (sEMG). METHODS: In this study, we enrolled 31 TMD patients (ranging from 18 to 26 years old, including 7 males and 24 females), first Fricton index was used to evaluate the clinical curative effect of TMD with the treatment of IMS stabilization splint; then CBCT was used to observe the TMJ condylar position changes of TMD before and after the treatment of IMS stabilization splint; finally sEMG was used to observe the changes of electromyography of anterior temporalis (AT) and masseter muscles (MM) of TMD before and after the treatment of IMS stabilization splint. RESULTS: The course of treatment was 6-8 months, with an average of 7.6 months. After the IMS stabilization splint treatment, TMD symptoms relieved, especially in pain, mandibular movement disorder, but still slightly inferior in the treatment of joint noise. And there was a statistically significant difference in the anterior and inner joint space, the condyle had the tendency of moving forward and outward. AT presented reduction significantly of EMG value at rest position after treatment. CONCLUSIONS: IMS stabilization splint is a therapeutic reversible treatment for TMD, especially for pain and mandibular movement disorder; it produces effects of forward and outward condylar movement and elimination of the masticatory muscles antagonism.

Nutritional Strategies for Chronic Craniofacial Pain and Temporomandibular Disorders: Current Clinical and Preclinical Insights.

This narrative review provides an overview of current knowledge on the impact of nutritional strategies on chronic craniofacial pain associated with temporomandibular disorders (TMDs). Individuals experiencing painful TMDs alter their dietary habits, avoiding certain foods, possibly due to chewing difficulties, which might lead to nutrient deficiencies. Our literature investigation revealed that the causal links between nutritional changes and craniofacial pain remain unclear. However, clinical and preclinical studies suggest that nutraceuticals, including vitamins, minerals, polyphenols, omega-3 fatty acids, isoprenoids, carotenoids, lectins, polysaccharides, glucosamines, and palmitoylethanolamides, could have beneficial effects on managing TMDs. This is described in 12 clinical and 38 preclinical articles since 2000. Clinical articles discussed the roles of vitamins, minerals, glucosamine, and palmitoylethanolamides. The other nutraceuticals were assessed solely in preclinical studies, using TMD models, mostly craniofacial inflammatory rodents, with 36 of the 38 articles published since 2013. Our investigation indicates that current evidence is insufficient to assess the efficacy of these nutraceuticals. However, the existing data suggest potential for therapeutic intervention in TMDs. Further support from longitudinal and randomized controlled studies and well-designed preclinical investigations is necessary to evaluate the efficacy of each nutraceutical intervention and understand their underlying mechanisms in TMDs.

Occlusal interventions for managing temporomandibular disorders.

BACKGROUND: Temporomandibular disorders (TMD) are conditions related to the musculoskeletal structure of the temporomandibular joint, which may lead to muscle or joint pain and other health issues. TMD may present in muscles only (myogenous), joints only (arthrogenous), or both (mixed), and may affect one side or both sides of the face. Myogenous TMD may present with or without limited mouth opening. Arthrogenous TMD may present as disc displacement with or without reduction ('reduction' meaning the articular disc resumes its normal position when the jaw is moving). Occlusal interventions change the occlusal relationship of maxillary and mandibular teeth to improve the alignment of the tooth contact, with the aim of relieving pain, and improving psychosocial functioning and quality of life. Occlusal interventions include splints and adjustments. Occlusal splints are specially designed mouth guards; they are generally classified as stabilisation, reflex or repositioning splints. Occlusal adjustment is the grinding down of teeth to improve occlusion. OBJECTIVES: To assess the effects of occlusal interventions in people diagnosed with temporomandibular disorders (TMD), compared to other interventions or no treatment, on joint pain, muscle pain at rest and when chewing, quality of life, discomfort, and recurrence. SEARCH METHODS: Cochrane Oral Health's Information Specialist searched following sources up to 9 August 2022: Cochrane Oral Health's Trials Register, Cochrane Central Register of Controlled Trials (CENTRAL), MEDLINE via Ovid, Embase via Ovid, and two trials registers. SELECTION CRITERIA: We included randomised controlled trials (RCTs) of occlusal interventions (splints or adjustment) for managing TMD compared with no treatment, placebo, occlusal splint with a different mechanism of action, or other active treatments. DATA COLLECTION AND ANALYSIS: We adopted standard Cochrane methods to select studies, extract and analyse data, assess the risk of bias in the studies, and judge the certainty of the evidence. We reported outcomes as short term (three months or less) or long term (more than three months). MAIN RESULTS: We included 57 studies (2846 participants) that compared occlusal splints with no treatment, placebo, or another treatment. Most of the studies evaluated full hard stabilisation splint (FHSS) as the occlusal splint. We judged only one study to be at low risk of bias. Our key outcomes of interest were self-reported joint pain when chewing, muscle pain at rest and when chewing, discomfort, severity and frequency of joint noise, and recurrence rate. The duration of the studies ranged from 5 weeks to 84 months. The key results presented below were measured between 4.4 weeks and 4 months. It is important to note that we have very low certainty in the evidence for all comparisons and outcomes assessed. There may be little to no difference in self-reported joint pain when chewing between occlusal splint (FHSS) and placebo (non-occlusal splint) (RR 1.88, 95% CI 0.94 to 3.75; 1 study, 60 participants with mixed TMD), or pharmacological therapy (diclofenac) (RR 2.10, 95% CI 0.83 to 5.30; 1 study, 29 participants with osteoarthritis), but the evidence is very uncertain. Occlusal splint (FHSS) may reduce muscle pain when chewing compared to no treatment (MD -1.97, 95% CI -2.37 to -1.57; 1 study, 84 participants with disc displacement without reduction), but may have little to no effect when compared to physical therapy (low-level laser) (RR 0.17, 95% CI 0.02 to 1.26; 1 study, 40 participants) or acupuncture (with needles) (MD 0.10, 95% CI -0.80 to 1.00, 1 study, 40 participants) in people with myofascial pain TMD, but the evidence is very uncertain. There may be little to no difference in muscle pain at rest when occlusal splint (FHSS) is compared to no treatment (MD -11.63, 95% CI -29.37 to 6.11; 1 study, 37 participants) or physical therapy (physiotherapy) (MD -0.19, 95% CI -1.25 to 0.87; 1 study, 72 participants) in myofascial pain TMD, but the evidence is very uncertain. There may be little to no difference in severity of joint noise when occlusal splint (FHSS) is compared to no treatment, but the evidence is very uncertain (MD -0.58, 95% CI -7.09 to 5.93; 1 study, 20 participants). When FHSS is compared to physical therapy (specifically, orofacial myofunctional therapy), physical therapy may reduce severity of joint noise, but the evidence is very uncertain (MD 5.92, 95% CI 0.18 to 11.66; 1 study, 20 participants with mixed TMD). There may be little to no difference in frequency of joint noise when occlusal splint (FHSS) is compared to placebo (non-occlusal splint) (RR 1.18, 95% CI 0.63 to 2.20; 1 study, 60 myofascial pain TMD participants), occlusal splint with a different mechanism of action (RR 0.80, 95% CI 0.07 to 9.18; 1 study, 9 participants with disc displacement with reduction), or physical therapy (jaw exercise) (RR 1.50, 95% CI 0.32 to 6.94; 1 study, 18 participants with myofascial pain TMD), but the evidence is very uncertain. Discomfort and recurrence rate were not reported in any study. We judged the certainty of the evidence to be very low for all outcomes in all comparisons due to limitations in study design and imprecision. AUTHORS' CONCLUSIONS: This review included 57 RCTs with 2846 participants, but the final results are inconclusive, so the research questions remain unanswered. Occlusal splints of the FHSS type may reduce muscle pain when chewing compared to no treatment, but the evidence is very uncertain. Orofacial myofunctional therapy may reduce severity of joint noise compared to occlusal splint (FHSS), but the evidence is very uncertain. For all other comparisons and outcomes, there may be little or no difference between groups, although the evidence is also very uncertain for these findings. Overall, we found insufficient evidence to reach conclusions regarding the effectiveness of occlusal interventions for managing symptoms of TMD, despite the available studies including almost 3000 participants. To make a useful contribution to the debate about the best way to treat TMD, any further research must be well-designed, with enough participants to reach the optimal information size for meaningful results; it requires recruitment from primary care, consensus around key outcomes and measures, and, ideally, long-term follow-up of three to five years, plus inclusion of a cost-effectiveness component.

The link between cutaneous allodynia and pain/sensitivity in teeth and gums during migraine episodes.

BACKGROUND: Migraine is one of the most common primary headaches worldwide, while toothache is the most common pain in the orofacial region. The association of migraine pain, and oral pain is unknown. This study aims to investigate the association between migraine and dental and gingival pain with the presence of allodynia. METHODS: A questionnaire comprising demographic data with the ID-Migraine (IDM) tool, an Allodynia Symptom Checklist (ASC), and inquiries about pain and sensitivity in the teeth and gums during migraine attacks was administered to the participants and 762 responded the survey. The study classified participants based on the ASC, and the relationship between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks was analyzed. The statistical analyses utilized Chi-square tests and the Fisher-Exact test. RESULTS: Among 762 migraine patients, 430 (56.44%) were classified as allodynia (+), while 332 (43.56%) were classified as allodynia (-) (p < 0.001). Additionally, 285 participants (37.5%) reported experiencing pain and sensitivity in the teeth and gums during migraine attacks, with a significant relationship observed between allodynia and pain/sensitivity in the teeth and/or gums during migraine attacks (p < 0.001). CONCLUSION: The findings of this study have important clinical implications. For migraine patients who are non-allodynic, the presence of pain and sensitivity in their teeth and gums during migraine attacks may indicate underlying dental diseases or the need for dental treatment especially root canal treatment. However, for allodynic patients, such symptoms may not necessarily indicate the presence of dental diseases or the need for dental treatment especially root canal treatment. These results underscore the significance of considering the presence of allodynia in the assessment and management of oral symptoms during migraine attacks.

Systemic Factors Affecting Pain Management in Dentistry.

There are several factors that affect a patient's experience of pain. These include both local and systemic factors. The systemic factors that affect patients' dental and orofacial pain experience include, but not limited to, hormonal, nutritional, systemic infections, neurodegenerative, and autoimmune, among others. Comprehensive medical history is essential to delineate any possible systemic factors affecting pain experience. A thorough review of systems should form the foundation, since multiple factors can affect the prognosis of pain management. This would facilitate early recognition and trigger prompt referrals to the appropriate medical professionals. This helps to reduce the health care burden.

Differential activation of lateral parabrachial nuclei and their limbic projections during head compared with body pain: A 7-Tesla functional magnetic resonance imaging study.

Pain is a complex experience that involves sensory, emotional, and motivational components. It has been suggested that pain arising from the head and orofacial regions evokes stronger emotional responses than pain from the body. Indeed, recent work in rodents reports different patterns of activation in ascending pain pathways during noxious stimulation of the skin of the face when compared to noxious stimulation of the body. Such differences may dictate different activation patterns in higher brain regions, specifically in those areas processing the affective component of pain. We aimed to use ultra-high field functional magnetic resonance imaging (fMRI at 7-Tesla) to determine whether noxious thermal stimuli applied to the surface of the face and body evoke differential activation patterns within the ascending pain pathway in awake humans (n=16). Compared to the body, noxious heat stimulation to the face evoked more widespread signal changes in prefrontal cortical regions and numerous brainstem and subcortical limbic areas. Moreover, facial pain evoked significantly different signal changes in the lateral parabrachial nucleus, substantia nigra, paraventricular hypothalamus, and paraventricular thalamus, to those evoked by body pain. These results are consistent with recent preclinical findings of differential activation in the brainstem and subcortical limbic nuclei and associated cortices during cutaneous pain of the face when compared with the body. The findings suggest one potential mechanism by which facial pain could evoke a greater emotional impact than that evoked by body pain.

Efficacy of botulinum neurotoxin A in persistent idiopathic dentoalveolar pain: a case series.

OBJECTIVES: Persistent idiopathic dentoalveolar pain (PIDP) is a challenging clinical entity associated with both physical and emotional consequences. Currently, the management is symptom-based and includes both topical and/or systemic treatments. More recently, botulinum neurotoxin-A (BONT-A) has been suggested as a treatment option. MATERIALS AND METHODS: We present a case series of 9 patients (5 female) with mean age 56 ± 15 diagnosed with PIDP. All patients reported prior experience with systemic drugs without a sufficient pain-relieving effect. BONT-A (BOTOX, Allergan) 100 U diluted with saline solution was used and the dose ranged from 20U to 50U distributed in 3 sites (intraoral and/or extraoral) per session. Patients underwent further injections (50U) monthly if pain severity measured using a Numerical Rating Scale (NRS 0-10) was still > 3 for 3 months. Pain severity and characteristics were recorded at baseline (T0), after 1 month (T1), 2 months (T2) and 3 months (T3). RESULTS: Mean pain intensity at baseline was NRS 6 (4-10). Latency before analgesic effect was at least 5-10 days after injection. Minor adverse effects were sickness and muscular hypotonia. Pain significantly reduced to NRS 4 (0-8) at T1, to NRS 2 (0-8) at T2 and to NRS 2 (NRS 0-8) at T3. Patients' functional variables (discomfort while chewing, talking, swallowing) were also recorded. CONCLUSIONS: BONT-A is widely used and although the exact mechanism of action remains unclear, it can be used effectively in reducing pain for a variety of conditions including PIDP. CLINICAL RELEVANCE: Our results suggest that BONT-A seems to be an alternative therapeutic approach for patients with PIDP.

Temporomandibular Joint Pain Measurement by Bite Force and Von Frey Filament Assays in Mice.

Temporomandibular joint (TMJ) pain and osteoarthritis (OA) are common and debilitating disorders that impair patients' quality of life. The mechanisms driving diseases-related pain are poorly understood, and current treatments fail to provide effective and long-term therapeutic effects. Additionally, pain assessment in research, particularly orofacial pain, poses several challenges that complicate studies in both clinical and basic science settings. Therefore, we have established an inflammatory TMJ pain mouse model via intra-articular injection of CFA (Complete Freund's Adjuvant) and evaluated pain behaviors by bite force measurement and the von Frey filament test. Mice with CFA injection exhibited orofacial pain behaviors compared to PBS injection, including reduced bite force and head withdrawal threshold in the von Frey filament test. These methods are relatively easy to execute to have reproducible results and can be potentially extended to pain studies for other disease models related to TMJ disorders. Together, bite force, and the von Frey filament tests are reliable in measuring orofacial pain, as demonstrated in CFA injection-induced painful TMJOA mouse models.

Efficacy of different low-level laser therapy sessions in the management of masseter muscle trigger points.

BACKGROUND: Low-level laser therapy (LLLT) is one of the recent treatment modalities for myofascial pain dysfunction syndrome with trigger points. The objective of the present study was to examine the impact of varying LLLT sessions on the treatment of masseter muscle trigger points. METHODS: 90 patients diagnosed with orofacial pain and trigger points in the masseter muscle for at least 6 months were selected and divided into 3 groups (n = 30) based on the number of LLLT sessions provided to patients. Patients in Group I received one session/per week, group II received two sessions/per week, and Group III received three sessions/per week. The sessions continued for 4 weeks, evaluations of pain levels, maximum mouth opening (MMO), and quality of life were conducted before and after the procedure at 1, 2, 3, 4, and 8 weeks. RESULTS: The pain scores exhibited a highly statistically significant difference among the three groups (p < 0.001) over the 8-week study period. MMO was statistically significantly different between groups at week 4 and week 8. The Oral Health Impact Profile-14 (OHIP-14) score was statistically significant difference between groups at week 8. The time showed a highly significant effect on the study outcomes within each group. CONCLUSION: Increased the number of LLLT sessions reduced the pain improved the MMO, and subsequently improved the quality of life. GOV ID: NCT06327204 - retrospectively registered.

Evaluation of the single and combined therapeutic effects of individually manufactured earplug therapy in patients with myogenous temporomandibular disorders: A randomized controlled clinical trial.

OBJECTIVE: To evaluate the effect of individually manufactured earplug therapy on pain intensity (PI), symptom severity (SS), and maximum mouth opening (MMO), in patients with myogenous temporomandibular disorders (TMD). METHODS: One-hundred-twenty patients were randomly allocated to six groups: Groups EP (earplug), OS (occlusal splint), EX (exercise), EPO (earplug with occlusal splint), EPE (earplug with exercise), and C (control). Outcomes were PI (assessed with a visual analog scale (VAS)), SS (assessed with the modified Symptom Severity Index Questionnaire (mSSI)), and MMO (evaluated with a digital caliper). Measurements were performed at T0 (before the therapy), T1 (1-month follow-up), and T2 (3-month follow-up). Data were analyzed using one-way analysis of variance (ANOVA), Tukey's HSD, and chi-square tests (alpha = 0.05). RESULTS: At T1 and T2, the greatest VAS and mSSI reduction was detected for the groups EPE (VAS = 5.3 ± 1.05, 3.3 ± 0.7; mSSI = 38.2 ± 2.27, 43.6 ± 3.94) and EPO (VAS = 5.2 ± 0.91, 3.2 ± 0.78; mSSI = 36.3 ± 3.97, 42.2 ± 3.19), respectively (p < 0.05). At T1, occlusal splint groups (groups OS (34.8 ± 2.97 mm) and EPO (33.8 ± 3.49 mm)) gave the highest MMO values, while T2 values did not constitute a significant difference with T1 (p > 0.05). CONCLUSIONS: The short-term use of combined earplug therapy resulted in a decrease in both PI and SS. Improvement in MMO in participants using occlusal splints was observed in the 1st month and was maintained through the 3rd month. CLINICAL RELEVANCE: Earplug therapy can be applied as a complementary therapy to occlusal splint and exercise treatments to decrease PI and SS in patients with myogenous TMD. To achieve functional recovery such as MMO, its combined use with splints should be taken into consideration by clinicians.

[28-year-old male patient with headaches on the left side and facial pain]. / 28-jähriger Patient mit in den Kiefer ausstrahlenden ­Kopfschmerzen temporal links.

INTRODUCTION: A 28-year-old male suffers for two weeks from new-onset very severe headache located on his left temple radiating to his jaw. He also complains about left sided retroorbital pain and chewing aggravated symptoms. In addition, nausea and emesis in the mornings during the past six months were reported. Clinical examination revealed tender swelling over the left temple, but laboratory results showed no signs of inflammation, normal electrolytes, kidney and liver values. A CT-scan revealed a circumscriptive osteolytic lesion in the left os temporale.

Treatment of temporomandibular joint internal derangement using MESNA injection.

INTRODUCTION: The development of temporomandibular disorders specifically emphasizes the biochemical changes occurring in the synovial fluid at different stages of temporomandibular joint disease. Research has indicated that inflammation may be a primary reason behind the pain and dysfunction in temporomandibular joint diseases. Since its clearance several years ago, MESNA (sodium 2-mercaptoethanesulfonate) has been used in various formulations as a mucolytic drug in the respiratory domain. It operates by disrupting the disulfide bonds present between polypeptide chains within mucus. MESNA exhibits minimal tissue distribution, with the material being swiftly and thoroughly eliminated via the kidneys. OBJECTIVES: To assess the efficacy of injecting MESNA directly into the Temporomandibular Joint to treat internal derangement. MATERIALS AND METHODS: A randomized clinical trial was conducted on sixty patients who exhibited non-responsiveness to conventional treatment and were diagnosed with TMJ anterior disc displacement with reduction. The patients were chosen from the outpatient clinic of the Oral and Maxillofacial Surgery Department at Tanta University Faculty of Dentistry. Two equal groups of patients were randomly assigned to each other. Group I (Mesna group) received intra-articular injection with MESNA solution. Group II (Standard group) received arthrocentesis with lactated ringer solution followed by injection of Hyaluronic Acid (HA). The data was gathered by functional examinations such as maximum interincisal opening (MIO) and clicking. A Visual Analogue Scale (VAS) assessed pain severity before and after treatments. RESULTS: Both MESNA and HA showed significant improvement up to six months of the follow-up compared to preoperative status, as evidenced by better mouth opening, lateral excursion, lower clicking, and reduced pain score in patients with TMDs. MESNA showed significant improvement during follow-up compared to HA. CONCLUSION: Compared to HA, MESNA showed a more noticeable improvement during the follow-up period.

Clinical profile in relation to age and gender of patients with temporomandibular disorders: a retrospective study.

BACKGROUND: The present study is to evaluate the clinical characteristics of patients with temporomandibular disorders (TMD). METHODS: A total of 3362 TMD patients were included. Each participant had complete medical records according to the diagnostic criteria for temporomandibular disorders (DC/TMD). The clinical characteristics including symptoms and signs in relation to age and gender were analyzed. RESULTS: The mean age of the patients seeking care was 29.89 ± 13.73Y, and 68.6% of patients were aged 16-35 years. The female-to-male ratio of patients was 2.2: 1, and the average age of males was significantly lower than that of females. The prevalence of clicking symptoms decreased with age, while the prevalence of pain symptoms and limitations in jaw movement increased with age. Females were more likely to have limitations in jaw movement than males. Among the patients with pain, the average visual analogue scale (VAS) was 2.96 ± 1.23. The average VAS score of acute TMD patients (≤ 3 months) was significantly higher than that of chronic TMD patients (> 3 months). CONCLUSIONS: The majority of TMD patients seeking care were young people. The number and average age of female patients was higher than the males. Female patients were more likely to have limitations in jaw movement than males.

Orofacial antinociceptive activity of codeine-associated geraniol in mice: a controlled triple-blind study.

This is a nonclinical, controlled, and triple-blind study to investigate the effects of codeine-associated geraniol on the modulation of orofacial nociception and its potential central nervous system depressing effect in an animal model. The orofacial antinociceptive activity of geraniol in combination with codeine was assessed through the following tests: (i) formalin-induced pain, (ii) glutamate-induced pain, and (iii) capsaicin-induced pain. Six animals were equally distributed into six groups and received the following treatments, given intraperitoneally (i.p.) 30 minutes before the experiments: a) geraniol/codeine 50/30 mg/kg; b) geraniol/codeine 50/15 mg/kg; c) geraniol/codeine 50/7.5 mg/kg; d) geraniol 50 mg/kg; e) codeine 30 mg/kg (positive control); or f) 0.9% sodium chloride (negative control). We performed pain behavior analysis after the injection of formalin (20 µL, 20%), glutamate (20 µL, 25 µM), and capsaicin (20 µL, 2.5 µg) into the paranasal region. Rubbing time of the paranasal region by the hind or front paw was used as a parameter. In the neurogenic phase of the formalin test, the geraniol/codeine at 50/7.5 mg/kg was able to promote the maximum antinociceptive effect, reducing nociception by 71.9% (p < 0.0001). In the inflammatory phase of the formalin test, geraniol/codeine at 50/30 mg/kg significantly reduced orofacial nociception (p < 0.005). In the glutamate test, geraniol/codeine at 50/30 mg/kg reduced the rubbing time by 54.2% and reduced nociception in the capsaicin test by 66.7% (p < 0.005). Geraniol alone or in combination does not promote nonspecific depressing effects on the central nervous system. Based on our findings, we suggest the possible synergy between geraniol and codeine in the modulation of orofacial pain.

Impact of streptozotocin-induced diabetes on experimental masseter pain in rats.

This study aimed to assess the influence of streptozotocin (STZ)-induced diabetes on the nociceptive behavior evoked by the injection of hypertonic saline (HS) into the masseter muscle of rats. Forty male rats were equally divided into four groups: a) isotonic saline control, which received 0.9% isotonic saline (IS), (Ctrl-IS); b) hypertonic saline control, which received 5% HS (Ctrl-HS); c) STZ-induced diabetic, which received IS, (STZ-IS); d) STZ-induced diabetic, which received HS (STZ-HS). Experimental diabetes was induced by a single intraperitoneal injection of STZ at dose of 60 mg/kg dissolved in 0.1 M citrate buffer, and 100 µL of HS or IS were injected into the left masseter to measure the nociceptive behavior. Later on, muscle RNA was extracted to measure the relative expression of the following cytokines: cyclooxygenase-2 (COX-2), tumor necrosis factor (TNF-α), and interleukins (IL)-1ß, -2, -6, and -10. One-way analysis of variance (ANOVA) was applied to the data (p < 0.050). We observed a main effect of group on the nociceptive response (ANOVA: F = 11.60, p < 0.001), where the Ctrl-HS group presented the highest response (p < 0.001). However, nociceptive response was similar among the Ctrl-IS, STZ-IS, and STZ-HS group (p > 0.050). In addition, the highest relative gene expression of TNF-α and IL-6 was found in the masseter of control rats following experimental muscle pain (p < 0.050). In conclusion, the loss of somatosensory function can be observed in deep orofacial tissues of STZ-induced diabetic rats.