Secondary bruxism: A valid diagnosis or just a coincidental finding of additional masticatory muscle activity? A narrative review of literature.

INTRODUCTION: Bruxism is defined as a repetitive masticatory muscle activity that can manifest it upon awakening (awake bruxism-AB) or during sleep (sleep bruxism-SB). Some forms of both, AB and SB can be associated to many other coexistent factors, considered of risk for the initiation and maintenance of the bruxism. Although controversial, the term 'secondary bruxism' has frequently been used to label these cases. The absence of an adequate definition of bruxism, the non-distinction between the circadian manifestations and the report of many different measurement techniques, however, are important factors to be considered when judging the literature findings. The use (and abuse) of drugs, caffeine, nicotine, alcohol and psychoactive substances, the presence of respiratory disorders during sleep, gastroesophageal reflux disorders and movement, neurological and psychiatric disorders are among these factors. The scarcity of controlled studies and the complexity and interactions among all aforementioned factors, unfortunately, does not allow to establish any causality or temporal association with SB and AB. The supposition that variables are related depends on different parameters, not clearly demonstrated in the available studies. OBJECTIVES: This narrative review aims at providing oral health care professionals with an update on the co-risk factors and disorders possibly associated with bruxism. In addition, the authors discuss the appropriateness of the term 'secondary bruxism' as a valid diagnostic category based on the available evidence. CONCLUSION: The absence of an adequate definition of bruxism, the non-distinction between the circadian manifestations and the report of many different measurement techniques found in many studies preclude any solid and convincing conclusion on the existence of the 'secondary' bruxism.

Sleep-related factors and orofacial pain symptoms associated with rhythmic masticatory muscle activity frequency scored by polysomnography recordings: A case-control study.

OBJECTIVE: This study aimed to evaluate the influence of the frequency of rhythmic masticatory muscle activity per hour (RMMA/h) scored by polysomnography (PSG) recordings on sleep-related factors and orofacial pain symptoms. METHODS: According to RMMA/h frequency, participants were assigned either to the control group (i.e., CRMMA, n = 40); or the case group according to high (i.e., HRMMA, n = 12) or low (LRMMA, n = 28) RMMA/h frequency. Fisher's exact (nominal variables), One-way Analysis of Variance followed by post-hoc Tukey (continuous variables) and Poisson Regression tests were used to calculate orofacial pain symptoms and sleep-related breathing, behavior, and architecture differences between controls versus cases at a significance level of 5%. RESULTS: The CRMMA differed from HRMMA and LRMMA subgroups considering orofacial pain, self-reported tooth clenching or grinding, obstructive sleep apnea (OSA), snoring, and most variables considering sleep architecture (P ≤ 0.05). Multivariate adjusted Poisson regression analysis revealed that bruxers, regardless of RMMA/h frequency, presented a significantly higher prevalence rate (PR) related to orofacial pain (PR 1.68; P = 0.025) and self-reported behavior (PR 1.71; P = 0.012). CONCLUSION: Significant differences in N1, N2 and N3 stages, arousals, arousal per hour, and sleep onset latency variables were found comparing bruxer with high or low RMMA/h frequency. Compared to controls, bruxers presented higher PR related to headache and self-reported tooth clenching or grinding.

Detrimental impact of temporomandibular disorders (mis)beliefs and possible strategies to overcome.

AIM: This topical review presents common patients' misbeliefs about temporomandibular disorders (TMD) and discusses their possible impact on the diagnosis, treatment and prognosis. We also discussed the possible influence of the beliefs and behaviours of healthcare providers on the beliefs of patients with TMD and suggested possible strategies to overcome the negative impacts of such misbeliefs. METHODS: This topical review was based on a non-systematic search for studies about the beliefs of patients and healthcare professionals about TMD in PubMed and Embase. RESULTS: Patients' beliefs can negatively impact the diagnosis, treatment and prognosis of TMD. These beliefs can be modulated by several factors such as culture, psychosocial aspects, gender, level of knowledge and previous experiences. Moreover, primary healthcare professionals, including dentists, may lack sufficient experience and skills regarding TMD diagnosis and treatment. Misbeliefs of the healthcare professionals can be based on outdated evidence that is not supported by rigorous methodological investigations. Education and dissemination of knowledge to patients and the general population are effective for prevention, promotion of health and disruption of the cycle of misinformation and dissemination of misbeliefs. CONCLUSION: The lack of basic information about TMD and the dissemination of mistaken and outdated concepts may delay the diagnosis, hinder the treatment, and consequently increase the risk of worsening the condition. Education is key to overcome TMD misbeliefs.

Psychophysical evaluation of somatosensory function in oro-facial pain: achievements and challenges.

AIM: This critical review describes key methodological aspects for a successful oro-facial psychophysical evaluation of the somatosensory system and highlights the diagnostic value of somatosensory assessment and management perspectives based on somatosensory profiling. METHODS: This topical review was based on a non-systematic search for studies about somatosensory evaluation in oro-facial pain in PubMed and Embase. RESULTS: The recent progress regarding the psychophysical evaluation of somatosensory function was largely possible due to the development and application of valid, reliable and standardised psychophysical methods. Qualitative sensory testing may be useful as a screening tool to rule out relevant somatosensory abnormalities. Nevertheless, the patient should preferably be referred to a more comprehensive assessment with the quantitative sensory testing battery if confirmation of somatosensory abnormalities is necessary. Moreover, the identification of relevant somatosensory alterations in chronic pain disorders that do not fulfil the current criteria to be regarded as neuropathic has also increased the usefulness of somatosensory evaluation as a feasible method to better characterise the patients and perhaps elucidate some underpinnings of the so-called 'nociplastic' pain disorders. Finally, an additional benefit of oro-facial pain treatment based on somatosensory profiling still needs to be demonstrated and convincing evidence of somatosensory findings as predictors of treatment efficacy in chronic oro-facial pain awaits further studies. CONCLUSION: Psychophysical evaluation of somatosensory function in oro-facial pain is still in its infancy but with a clear potential to continue to improve the assessment, diagnosis and management of oro-facial pain patients.

Frequency of awake bruxism behaviour in orthodontic patients: Randomised clinical trial: Awake bruxism behaviour in orthodontic patients.

INTRODUCTION: The influence of aligners on the activity of the masticatory muscles is still controversial, especially regarding the behaviour associated with awake bruxism (AB). OBJECTIVE: To compare the frequency of AB behaviours between patients treated with aligners and fixed appliances. METHODS: The sample comprised 38 Class I patients (mean age 22.08 years), divided by simple randomisation into two groups: OA group; orthodontic aligners (n 19) and FA group; fixed appliance (n 19). The frequency of AB was investigated by the ecological momentary assessment using an online device (mentimeter), during 7 following days at different timepoints, before and after appliance placement and in the 2nd, 3rd, 4th and 6th months of orthodontic treatment. These variables were also evaluated: level of anxiety by the State-Trait Anxiety Inventory, stress by the Perceived Stress Scale, catastrophising related to pain and degree of hypervigilance by the Pain Vigilance and Awareness Questionnaire, and the presence of facial pain evaluated by the DC/TMD. RESULTS: There was no difference between groups in the frequency of AB behaviours, with mean of 53.5% for group OA and 51.3% for FA. The most frequent behaviour was slightly touching the teeth, and in FA group, there was a significant reduction in this behaviour soon after appliance placement. The groups did not differ concerning the degree of anxiety, stress, catastrophising, hypervigilance and facial pain. CONCLUSION: The orthodontic treatment performed with aligners or fixed appliances did not influence the frequency of AB during the 6 months of treatment. REGISTRY OF CLINICAL TRIALS: (REBEC): RBR-9zytwf.

CYP450 polymorphisms and clinical pharmacogenetics of ibuprofen after lower third molar extraction.

PURPOSE: This study hypothesized that drugs accumulate in the bloodstream of poor-metabolizing patients and may have more adverse effects and different pain perceptions and aimed to investigate the influence of CYP450 polymorphisms on acute postoperative pain, swelling, and trismus controlled by ibuprofen (600 mg) in 200 volunteers after dental extraction. In addition, surgical outcomes can determine pain, edema, and trismus and indicate inflammatory reactions after oral surgeries. METHODS: Genetic sequencing was performed to identify CYP450 polymorphisms and the surgical parameters evaluated: pre and postoperative swelling, trismus, and temperature; self-reported postoperative pain with visual analog scale (VAS); rescue medication consumed; and severity of adverse reactions. RESULTS: A multiple linear regression model with independent variables [single nucleotide polymorphisms (SNPs), BMI (body mass index), duration, and difficulty of surgery] and dependent variables [postoperative pain by sum of pain intensity difference (SPID), trismus, and swelling] was used for analysis. The duration of surgery was a predictor for pain at 8 h and 96 h after surgery, and BMI was a predictor for both swelling and trismus on the 2nd postoperative day. When evaluating CYP2C8 and C9 genotyped SNPs, it was observed that normal metabolizers showed higher pain levels than the intermediate/poor metabolizers on the postoperative periods as compared with time 0 h. In another analysis, the poor metabolizers for CYP2C8 and C9 presented lower levels of postoperative pain after 8 h and used rescue medication earlier than normal metabolizers. CONCLUSION: Ibuprofen 600 mg was very effective in controlling inflammatory pain after lower third molar surgeries, without relevant adverse reactions; although in a very subtle way, patients with poor metabolism had higher levels of pain in the first hours, and no longer after 8 h, and used pain relief medication earlier. TRIAL REGISTRATION: The study was registered with ClinicalTrials.gov ID (NCT03169127), on March 16th, 2017.

Influence of Reported Physical Activity Level and Psychosocial Features on Orofacial Mechanical Sensitivity: A Pilot Study.

AIMS: To evaluate the influence of self-reported physical activity level on painful mechanical somatosensory profile and psychosocial characteristics. METHODS: A total of 90 participants, male and female, were divided into three groups based on the frequency, duration, and intensity of physical activity over the last 3 months. The classification followed a modified criterion of the short version of the International Physical Activity Questionnaire (IPAQ). Mechanical quantitative sensory tests were performed in the region of the anterior temporalis muscle and on the thenar area of the dominant hand, and psychosocial aspects were assessed using questionnaires measuring state and trait anxiety, pain catastrophizing, lifestyle, and quality of life. RESULTS: There was no significant main effect of group on any of the somatosensory variables (F < 0.34 and P > .416). As for psychosocial aspects, the low level of physical activity group had the lowest scores on the lifestyle questionnaire (P < .009). CONCLUSION: Level of physical activity did not significantly influence mechanical somatosensory thresholds or temporal summation in the orofacial region, and worse quality of life was found in participants reporting a low level of physical activity.

Local anaesthesia decreases nerve growth factor induced masseter hyperalgesia.

The aim of this investigation was to evaluate the effects of local anaesthesia on nerve growth factor (NGF) induced masseter hyperalgesia. Healthy participants randomly received an injection into the right masseter muscle of either isotonic saline (IS) given as a single injection (n = 15) or an injection of NGF (n = 30) followed by a second injection of lidocaine (NGF + lidocaine; n = 15) or IS (NGF + IS; n = 15) in the same muscle 48 h later. Mechanical sensitivity scores of the right and left masseter, referred sensations and jaw pain intensity and jaw function were assessed at baseline, 48 h after the first injection, 5 min after the second injection and 72 h after the first injection. NGF caused significant jaw pain evoked by chewing at 48 and 72 h after the first injection when compared to the IS group, but without significant differences between the NGF + lidocaine and NGF + IS groups. However, the mechanical sensitivity of the right masseter 5 min after the second injection in the NGF + lidocaine group was significantly lower than the second injection in the NGF + IS and was similar to the IS group. There were no significant differences for the referred sensations. Local anaesthetics may provide relevant information regarding the contribution of peripheral mechanisms in the maintenance of persistent musculoskeletal pain.

Intraoral Somatosensory Alterations Impact Pulp Sensibility Testing in Patients with Symptomatic Irreversible Pulpitis.

INTRODUCTION: This case-control study aimed to compare trigeminal somatosensory sensitivity between patients with a clinical diagnosis of symptomatic irreversible pulpitis (n = 33) and healthy participants (n = 33) and to evaluate the impact of somatosensory stratification of symptomatic irreversible pulpitis on pulp sensibility testing. METHODS: A standardized battery of qualitative sensory assessment measured intra- and extraoral sensitivity to touch, cold, and pinprick stimuli. Dental pain intensity (0-100, numeric rating scale) and duration (seconds) evoked by cold stimuli (refrigerant spray) were applied to, respectively, the nonaffected and affected tooth (cases) and the upper right and left premolars (controls); z score transformation, analysis of variance (ANOVA), and chi-square tests were applied to the data (P = .050). RESULTS: Patients with irreversible pulpitis reported intraoral hypersensitivity more frequently than healthy participants (58% and 33%, respectively; P < .05). In addition, patients with irreversible pulpitis reported higher z scores of pain intensity (ANOVA main effects, F = 37.10, P < .05, partial η2 = 0.37) and duration (ANOVA main effects F = 23.3, P < .05, partial η2 = 0.27) after the pulp sensibility test compared with healthy participants. Nevertheless, subgroup analysis taking into account the presence of intraoral hypersensitivity indicated that the pain lingered most for patients with symptomatic irreversible pulpitis who also presented intraoral hypersensitivity (Tukey test, P < .05) but with no differences between patients with irreversible pulpitis without intraoral hypersensitivity and healthy participants (Tukey test, P > .05). CONCLUSIONS: QualST is able to detect intraoral alterations in patients with symptomatic irreversible pulpitis that seem useful to stratify the patients into distinct subgroups. Therefore, somatosensory assessment of the adjacent tissues may provide diagnostic fine-tuning of dental pulp diseases.

Topical anaesthesia degree is reduced in temporomandibular disorders patients: A novel approach to assess underlying mechanisms of the somatosensory alterations.

BACKGROUND: Changes in quantitative sensory testing (QST) parameters following topical anaesthesia could contribute to better elucidate underlying mechanisms of somatosensory alterations in temporomandibular disorder (TMD) pain patients. This placebo-controlled crossover investigation compared the somatosensory profile following topical anaesthesia between TMD patients (n = 20) and healthy participants (n = 20). METHODS: Cold detection threshold, warm detection threshold, cold pain threshold, heat pain threshold, mechanical detection threshold, mechanical pain threshold, wind-up ratio and pressure pain threshold were assessed on the skin overlying the masseter at three consecutive days (baseline and immediately after lidocaine 4%/placebo cream). Mixed ANOVA and a coding system that accounts for the diversity of types of peripheral axons associated with the somatosensory parameters were applied for data analysis. RESULTS: The lidocaine application caused no changes in the somatosensory sensitivity in the masseter region in TMD patients (P > .050), but sensitivity to cold, cold pain, touch and pinprick stimuli were reduced after topical anaesthesia in healthy participants (P < .050). Also, the degree of topical anaesthesia was greater in healthy participants (P = .008). The coding system suggested that TMD patients presented only Aδ-fibre block, whereas a combination of either Aß- and/or C-fibre block was observed in 35% of healthy participants in addition to Aδ-fibre block following lidocaine application. CONCLUSION: Quantitative sensory testing can be successfully applied to identify meaningful differences in the degree of hypoalgesia and hypoesthesia following short-time topical anaesthesia.

Masseter corticomotor excitability is decreased after intramuscular administration of nerve growth factor.

BACKGROUND: Quantification of motor-evoked potentials (MEPs) can contribute to better elucidate the central modulation of motor pathways in response to nociceptive inputs. The primary aim of this study was to assess the modulatory effects of nerve growth factor (NGF) injection on masseter corticomotor excitability. METHODS: The healthy participants of this randomized, double blind placebo-controlled experiment were assigned to have injected into the right masseter muscle either NGF (n = 25) or isotonic saline (IS, n = 17). The following variables were assessed at baseline and 48 hr after the injection: right masseter MEP amplitude and corticomotor mapping and clinical assessment of jaw pain intensity and function. Repeated Measures ANOVA was applied to the data. RESULTS: NGF caused jaw pain and increased jaw functional disability after the injection (p < 0.050). Also, the participants in the NGF group decreased the MEP amplitude (p < 0.001) but the IS group did not present any significant modulation after the injection (p > 0.050). Likewise, the participants in the NGF group reduced corticomotor map area and volume (p < 0.001), but the IS group did not show any significant corticomotor mapping changes after the injection (p > 0.050). Finally, there was a significant correlation between the magnitude of decreased corticomotor excitability and jaw pain intensity on chewing 48 hr after the NGF injection (r = -0.51, p = 0.009). CONCLUSION: NGF-induced masseter muscle soreness can significantly reduce jaw muscle corticomotor excitability, which in turn is associated with lower jaw pain intensity and substantiates the occurrence of central changes that most likely aim to protect the musculoskeletal orofacial structures. SIGNIFICANCE: Intramuscular administration of nerve growth factor into masseter muscle causes inhibitory corticomotor plasticity, which likely occurs to prevent further damage and seems associated with lower pain intensity on function.

The effect of orthodontic separator and short-term fixed orthodontic appliance on inflammatory mediators and somatosensory function.

BACKGROUND: Although inflammation can alter cytokines release and nerve function, it is not yet fully established if orthodontic-induced inflammation can cause significant extraoral trigeminal somatosensory alterations and release of inflammatory chemical mediators. OBJECTIVE: The primary aim of this study was to investigate the impact of orthodontic separator and short-term fixed orthodontic appliance on the extraoral trigeminal somatosensory function and concentrations of cytokines in the gingival crevicular fluid (GCF). METHODS: Twenty-two female patients were evaluated as follow: baseline, 24 hour-after elastomeric separator (-aES), 24 hour- and 1 month-after bonding brackets (-aBB) at both arches. The outcome variables were as follows: self-reported pain (Visual Analog Scale), QSTs (current perception threshold-CPT, cold detection threshold-CDT, warm detection threshold-WDT, mechanical detection threshold-MDT, mechanical suprathreshold-MST and wind-up ratio-WUR. All QSTs were performed at infra-orbital and mental nerve entry zone at patient`s dominant side. In addition, GCF samples in order to assess cytokines profile (IL-1ß,IL-8,IL-6 and TNF-α) were collected. ANOVA and Tukey's post hoc analyses were performed (a = 5%). RESULTS: Patients reported higher pain intensity 24 hour-aBB compared to baseline and 24 hour-aES (P < 0.050). Patients were less sensitive to pin-prick pain (MST) at 24 hour-aBB and 1 month-aBB compared to baseline (P < 0.006). Significant increases in IL-6 levels were observed 24 hour-aBB (P < 0.001). Multiple comparison analysis showed significant increase in IL-1ß levels (P < 0.001) and TNF-α (P < 0.001) 1 month-aBB compared to baseline. CONCLUSION: Elastomeric separators only induced mild pain and were not able to significantly increase proinflammatory cytokines level in the GCF. In addition, orthodontic fixed appliance may induce only minor somatosensory changes at extraoral trigeminal locations.

Does electrode placement influence tens-induced antihyperalgesia in experimental inflammatory pain model?

BACKGROUND: Transcutaneous electrical nerve stimulation (TENS) is a treatment commonly used for managing pain; however, the ideal placement of the electrodes is not fully understood. OBJECTIVE: To investigate the best way to apply TENS electrodes in an experimental inflammatory pain model. METHOD: Knee joint inflammation was induced in rats, followed by administration of low-frequency TENS (4Hz) under anesthesia for five days. Animals were randomly allocated to five groups according to electrode placement (n=6, each): dermatome, contralateral, paraspinal, acupoint, and control. INTERVENTIONS: Low-frequency TENS at sensory intensity and 100µs pulse duration. Withdrawal thresholds to mechanical (von Frey) and thermal stimuli and joint edema were assessed before induction of inflammation and immediately before and after application of TENS. RESULTS: Reduced paw withdrawal threshold and thermal latency that occur 24h after the induction of inflammation were significantly reversed by the administration of TENS in all groups when compared with sham treatment or with the condition before TENS treatment. No difference was observed in the edema measurement. CONCLUSION: These results offer more options for practitioners to choose the area of the body most commodious for electrode placement, depending on the clinical condition of the patient, because the effect was similar at all sites. In addition, there was a loss of the effectiveness of TENS in reversing mechanical and thermal hyperalgesia on the fifth day, suggesting the development of the tolerance phenomenon.

Natural products assessed in animal models for orofacial pain – a systematic review

ABSTRACT Orofacial pain is related to tissues of the head, face, neck and all the intraoral structures; it is rather debilitating to the patient and also difficult to treat. There are relatively few studies dedicated to the use of natural products to alleviate orofacial pain in preclinical experiment models (performed in experimental animals which provide support for clinical trials). Main objectives of the present systematic review summarize the studies on natural products assessed in animal models for orofacial pain seeking to give evidence to future development of new pharmaceutical products to manage the orofacial pain. Our review includes a thorough search of literature using the terms of orofacial pain, facial pain, medicinal plants and natural products. This search was performed using to retrieve English language articles in Medline-PubMed, Scopus and Web of Science. A total of eighteen studies were included in our survey for the inclusion criteria. Firstly, this review identified 210 citations from electronic search, after removal of duplicates and screening for relevant titles and abstracts, a total of eighteen articles were selected to the inclusion criteria established. Our findings suggest that natural products can be a promising or a trump tool for the development of new drugs to treat orofacial pain conditions, but the researchers that deal with experimental preclinical trials of new drugs (including natural products or synthetic drugs) for orofacial pain conditions urgently need to show translational evidence (with clinical approach) of these compounds.

Orofacial antinociceptive effect of the ethanolic extract of Annona vepretorum Mart. (Annonaceae).

Annona vepretorum Mart. (Annonaceae) is a species popularly known in Brazil as "araticum" and "pinha da Caatinga". We have evaluated the antinociceptive effects of A. vepretorum in formalin-, capsaicin-, and glutamate-induced orofacial nociception in mice. Male Swiss mice were pretreated with either saline (p.o.), A. vepretorum ethanol extract (Av-EtOH 25, 50 and 100 mg/kg, p.o.), or morphine (10 mg/kg, i.p.), before formalin, capsaicin, or glutamate was injected into the right upper lip. Pre-treatment with Av-EtOH at all doses produced a reduction in face-rubbing behavior induced by formalin in both phases, and these pre-treatments also produced a significant antinociceptive effect in the capsaicin and glutamate tests. Pre-treatment with naloxone (1.5 mg/kg, i.p.) did not reverse the antinociceptive activity of the extract at the dose of 100 mg/kg in the first phase of this test. Our results suggest that Av-EtOH might be useful in the treatment of orofacial pain.

Characterization and Antihypertensive Effect of the Complex of (-)-ß- pinene in ß-cyclodextrin.

This work aimed to characterize and evaluate the antihypertensive effect of the (-)-ß-pinene/ß-cyclodextrin (ßP/ß-CD) complex. The complex was prepared through physical mixture and slurry complexation methods and was analyzed through differential scanning calorimetry, thermogravimetry/derivative thermogravimetry, fourier transform infrared spectroscopy, diffraction X-ray, docking and scanning electron microscopy. Normotensive or L-NAME-induced hypertensive rats were used in pharmacological experiments. Mean arterial pressure (MAP) was determined with direct blood pressure measurements from the abdominal aorta. The drugs were orally administrated and their effects were recorded during 48 hours. Vascular effects of ßP were evaluated in isolated ring of mesenteric artery. The physicochemical characterization showed ßP/ß-CD complex formation. In hypertensive rats (MAP = 156±16 mmHg), the complex, but not ßP alone, promoted hypotension at 36 and 48 hours after administration (MAP = 124±3 and 110±5 mmHg, respectively). In arterial rings, ßP vasorelaxed rings precontracted with phenylephrine (Emax = 105±6%), which was not changed after the removal of the vascular endothelium (Emax = 108±4%), after the pre-contraction with KCl 80 mM (Emax = 107±8%) or S(-)-BayK8644 (Emax = 107±5%), or after incubation with TEA (Emax = 113±4%). Finally, ßP inhibited CaCl2- and sodium-orthovanadate-induced contractions. In conclusion, the slurry complexation method was the best among them. Pharmacological results demonstrated that the complex promoted antihypertensive effect. Furthermore, ßP induced endothelium- independent vasorelaxation possibly caused by the inhibition of the Ca2+ influx through L-type Ca2+ channel associated to a decrease in calcium sensitivity.

Linalool and linalool complexed in ß-cyclodextrin produce anti-hyperalgesic activity and increase Fos protein expression in animal model for fibromyalgia.

The analgesic activity of (-)-linalool (LIN), a monoterpene present in essential oils of Lamiaceae species, has been previously demonstrated in rodents. However, its possible use in the treatment of fibromyalgia (FM) was never demonstrated. Additionally, as a short half-life is a limitation for the LIN medicinal application, the employment of drug delivery systems has been used to improve pharmaceutical properties of this compound. We investigated the anti-nociceptive effect of LIN, isolated or in ß-cyclodextrin complex (LIN-CD), in an animal model of chronic non-inflammatory muscle pain (a FM animal model), as well as its effect on the central nervous system (CNS). Male Swiss mice were subjected to two injections of acidic saline (pH 4; 20 µL/gastrocnemius) and were treated on alternate days, with LIN-CD (25 mg/kg, p.o.), LIN (25 mg/kg, p.o.), tramadol (TRM 4 mg/kg, i.p.), or vehicle (neutral saline). After 60 min, they were screened for mechanical hyperalgesia (von Frey), motor coordination (rotarod), and muscle strength (grip strength meter) for 27 days. The CNS areas involved in the anti-hyperalgesic activity were evaluated by immunofluorescence. LIN or LIN-CD produced a significant reduction (p < 0.001) of mechanical hyperalgesia on chronic non-inflammatory muscle pain model, which remained for 24 h only in LIN-CD, and these compounds significantly (p < 0.05) activated neurons of the locus coeruleus, nucleus raphe magnus, and periaqueductal gray areas. So, our results suggest that LIN-CD improved analgesic profile of LIN, with a probable involvement of descending pain pathways and the anti-nociceptive effect of linalool in an animal model of chronic non-inflammatory muscle pain. So far, only the investigations in animal models of inflammatory pain and supraspinatus were published.

Contingent electrical stimulation inhibits jaw muscle activity during sleep but not pain intensity or masticatory muscle pressure pain threshold in self-reported bruxers: a pilot study.

OBJECTIVE: This study investigated the effect of contingent electrical stimulation (CES) on present pain intensity (PI), pressure pain threshold (PPT), and electromyographic events per hour of sleep (EMG/h) on probable bruxers with masticatory myofascial pain. STUDY DESIGN: The study enrolled 15 probable bruxers with masticatory myofascial pain in 3 phases: (1) baseline EMG/h recording, (2) biofeedback treatment using a CES paradigm (active group, n = 7) or inactive device (control group, n = 8), and (3) posttreatment EMG/h recording. PI and PPT were assessed after each phase. Analysis of variance models were used to compare results at a 5% significance level. RESULTS: Patients in the active group had 35% lower EMG/h in P2 and 38.4% lower EMG/h in P3, when compared with baseline. There were no differences in PI or PPT levels at any phase. CONCLUSIONS: CES could reduce EMG activity associated with sleep bruxism in patients with masticatory myofascial pain but did not influence perceived pain.

ß-cyclodextrin complex containing Lippia grata leaf essential oil reduces orofacial nociception in mice - evidence of possible involvement of descending inhibitory pain modulation pathway.

The treatment of orofacial pain remains a major challenge for modern medicine. Thus, we prepared and physicochemically characterized a new ß-cyclodextrin complex containing Lippia grata leaf essential oil (ß-CD/EO) to investigate their possible antinociceptive activity in animal models of orofacial pain. The results of Differential scanning calorimeter (DSC) and Thermogravimetry/derivative thermogravimetry (TG/DTG) showed that the products prepared by Slurry complexation (SC) method were able to incorporate greater amounts of EO. In the X-ray diffractogram, it was shown that complex between EO and ß-CD was formed. Male Swiss mice were pre-treated with ß-CD/EO (6, 12 or 24 mg/kg, per os, gavage, p.o.), morphine (5 mg/kg, i.p.) or vehicle (distilled water, p.o.) 1 hr before treatment with formalin (20 µL, 2%), capsaicin (20 µL, 2.5 µg) or glutamate (40 µL, 25 µM) into the right upper lip. Our results demonstrated that p.o. treatment with ß-CD/EO was significantly (p < 0.05 or p < 0.001) capable of reducing the nociceptive face-rubbing behaviour in both phases of the formalin test. ß-CD/EO-treated mice were also significantly (p < 0.05 or p < 0.001) protected against nociception induced by capsaicin and glutamate. For the action in the central nervous system (CNS), ninety minutes after the treatment, the mice were perfused, the brains collected, crioprotected, cut in a criostate and submitted to an immunofluorescence protocol for Fos protein. The immunofluorescence protocol demonstrated that the ß-CD/EO significantly activated (p < 0.05; p < 0.01 or p < 0.001) the motor cortex, the Locus ceruleus, the nucleus raphe magnus and the periaqueductal gray of the CNS. These effects apparently did not alter, in tested doses, the motor coordination of mice in the rota-rod test. Our results proposed that ß-CD/EO might present an important draft of drug to the study of new compounds for the treatment of orofacial pain.

Evaluation of wound healing activity of atranorin, a lichen secondary metabolite, on rodents

The aim of this study was to investigate the wound healing activity of atranorin cream (Patent requested) on excision wounds. Seventy-two male rats were anesthetized and an excisional wound was performed. Then the rats were randomly assigned into three groups: untreated control group; atranorin 1 (group treated with 1% AT ointment); and atranorin 5 (group treated with 5% AT ointment). Six animals of each group were euthanized 3, 7, 14 or 21 days after surgical procedures and the wounded areas were analyzed and removed. Serial histological sections were obtained and stained by histochemical techniques (Hematoxilin-Eosin-HEand Sirius red) and immunohistochemical techniques. Topical application of atranorin reduced wound areas, induced earlier granulation tissue formation, increased cell proliferation, improved collagenization and modulated the myofibroblasts differentiation when compared to control animals. It is suggested that atranorin modulates the wound healing process. These data suggest that this formulation based on atranorin extracted from Cladina kalbii AHTI may be a new biotechnological product for wound healing clinical applications.