Methyl jasmonate ameliorates pain-induced learning and memory impairments through regulating the expression of genes involved in neuroinflammation.

OBJECTIVE: Orofacial pain with high prevalence is one of the substantial human health issues. The importance of this matter became more apparent when it was revealed that orofacial pain, directly and indirectly, affects cognition performances. Currently, researchers have focused on investigating pharmaceutics to alleviate pain and ameliorate its subsequent cognitive impairments. DESIGN: In this study, the rats were first treated with the central administration of methyl jasmonate (MeJA), which is an antioxidant and anti-inflammatory bio-compound. After 20 min, orofacial pain was induced in the rats by the injection of capsaicin in their dental pulp. Subsequently, the animals' pain behaviors were analyzed, and the effects of pain and MeJA treatments on rats learning and memory were evaluated/compared using the Morris water maze (MWM) test. In addition, the expression of tumor necrosis factor-α (TNF-α), IL-1ß, BDNF, and COX-2 genes in the rats' hippocampus was evaluated using real-time polymerase chain reaction. RESULTS: Experiencing orofacial pain resulted in a significant decline in the rats learning and memory. However, the central administration of 20 µg/rat of MeJA effectively mitigated these impairments. In the MWM, the performance of the MeJA-treated rats showed a two- to threefold improvement compared to the nontreated ones. Moreover, in the hippocampus of pain-induced rats, the expression of pro-inflammatory factors TNF-α, IL-1ß, and COX-2 significantly increased, whereas the BDNF expression decreased. In contrast, MeJA downregulated the pro-inflammatory factors and upregulated the BDNF by more than 50%. CONCLUSIONS: These findings highlight the notable antinociceptive potential of MeJA and its ability to inhibit pain-induced learning and memory dysfunction through its anti-inflammatory effect.

Sex differences in carbamazepine effects in a rat model of trigeminal neuropathic pain.

Carbamazepine (CBZ) represents the first-line treatment for trigeminal neuralgia, a condition of facial pain that affects mainly women. The chronic constriction of the infraorbital nerve (CCI-ION) is a widely used model to study this condition, but most studies do not include females. Thus, this study aimed to characterize sensory and affective changes in female rats after CCI-ION and compare the effect of CBZ in both sexes. Mechanical allodynia was assessed 15 days after CCI-ION surgery in rats treated with CBZ (10 and 30 mg/kg, i.p.) or vehicle, together with the open-field test. Independent groups were tested on the Conditioned Place Preference (CPP) paradigm and ultrasonic vocalization (USV) analysis. Blood samples were collected for dosage of the main CBZ metabolite. CBZ at 30 mg/kg impaired locomotion of CCI-ION male and sham and CCI-ION female rats and resulted in significantly higher plasma concentrations of 10-11-EPX-CBZ in the latter. Only male CCI-ION rats showed increased facial grooming which was significantly reduced by CBZ at 10 mg/kg. CBZ at 10 mg/kg significantly reduced mechanical allodynia and induced CPP only in female CCI-ION rats. Also, female CCI-ION showed reduced emission of appetitive USV but did not show anxiety-like behavior. In conclusion, male and female CCI-ION rats presented differences in the expression of the affective-motivational pain component and CBZ was more effective in females than males. Further studies using both sexes in trigeminal neuropathic pain models are warranted for a better understanding of potential differences in the pathophysiological mechanisms and efficacy of pharmacological treatments.

Does the Use of Botulinum Toxin in Treatment of Myofascial Pain Disorder of the Masseters and Temporalis Muscles Reduce Pain, Improve Function, or Enhance Quality of Life?

BACKGROUND: The efficacy of botulinum toxin for management of myofascial pain disorder (MPD) remains controversial. PURPOSE: The purpose was to determine if the use of onabotulinumtoxinA (onabotA) in patients with MPD reduces pain, improves function, or enhances quality of life (QoL). STUDY DESIGN, SETTING, AND SAMPLE: This is a multicenter, prospective, randomized, double-blinded, placebo-controlled clinical trial. Subjects with orofacial pain were screened for MPD as defined by the Diagnostic Criteria for Temporomandibular Disorders. PREDICTOR VARIABLE: The primary predictor variable was MPD treatment with random assignment to onabotA or placebo (saline). MAIN OUTCOME VARIABLE: The primary outcome variable was pain before treatment (T0) and at 1 month (T1) using a visual analog scale. Secondary outcome variables included pain at 2 months (T2) and 3 months (T3), maximal incisal opening (MIO), jaw function (jaw functional limitation scale), and QoL (Short Form 36) measured at T0, T1, T2, and T3. COVARIATES: Covariates included subject demographics, prior treatments, and temporomandibular joint signs/symptoms. ANALYSES: Descriptive and bivariate statistics included χ2 test, Fisher's exact test, or t-test. RESULTS: Seventy five subjects with a mean age of 37 (±11) and 35 (±12) years in the onabotA and placebo groups, respectively (P = .6). Females represented 32 (86%) and 29 (76%), respectively (P = .3). Mean visual analog scale pain score in the onabotA group was 58 (±15), 39 (±24), 38 (±23), and 38 (±20) at T0, T1, T2, and T3, respectively; and the placebo group was 54 (±14), 40 (±23), 34 (±20), and 36 (±22) at T0, T1, T2, and T3, respectively. There was no statistically significant difference in pain between groups at any time point (P = .36). There was no statistically significant difference between groups in MIO (P = .124), jaw function (P = .236), or QoL domains (P > .05) at any time point. Within-group improvement in pain was seen in both groups (P < .005). Within-group improvement in jaw function was seen in the onabotA (P = .007) and placebo (P = .005) groups. There was no within-group improvement in MIO or QoL with either group (P > .05). CONCLUSIONS: OnabotA and saline (placebo) injections both decrease pain and improve jaw function in subjects with MPD.

Exogenous histamine and H 2 receptor activation and H 3 receptor inhibition in nucleus accumbens modulate formalin-induced orofacial nociception through opioid receptors.

It has been demonstrated that the nucleus accumbens (NAc) plays an important role in modulation of nociception due to its extensive connections with different regions of the brain. In addition, this nucleus receives histaminergic projections from tuberomammillary nucleus. Considering the role of the central histaminergic system in nociception, the effect of histamine and its H 2 and H 3 receptors agonist and antagonist microinjections into the NAc on orofacial formalin nociception was investigated. In male Wistar rats, using stereotaxic surgery, two guide cannulas were bilaterally implanted into the right and left sides of the NAc. Diluted formalin solution (1.5%, 50 µl) injection into the vibrissa pad led to orofacial nociception. Immediately after injection, face rubbing was observed at 3-min blocks for 45 min. Orofacial formalin nociception was characterized by a biphasic nociceptive response (first phase: 0-3 min and second phase: 15-33 min). Microinjections of histamine (0.5 and 1 µg/site), dimaprit (1 µg/site, H 2 receptor agonist) and thioperamide (2 µg/site, H 3 receptor antagonist) attenuated both phases of formalin orofacial nociception. Prior microinjection of famotidine (2 µg/site) inhibited the antinociceptive effects of dimaprit (1 µg/site). Furthermore, comicroinjection of thioperamide (2 µg/site) and immepip (1 µg/site) prevented thioperamide (2 µg/site)-induced antinociception. Naloxone (2 µg/site) also prevented histamine, dimaprit- and thioperamide-induced antinociception. The results of this study demonstrate that at the level of the NAc, histamine and its H 2 and H 3 receptors are probably involved in the modulation of orofacial nociception with an opioid system-dependent mechanism.

Analgesic effect of linalool odor on oral ulcerative mucositis-induced pain in rats.

Oral ulcerative mucositis (OUM) induces severe pain, leading to a low quality of life. Linalool odor exposure has recently been reported to suppress inflammatory pain in the hind paws. However, the analgesic effect of linalool odor on orofacial pain remains unclear. In this study, we examined the mechanism underlying the analgesic effect of linalool odor on oral pain caused by OUM using nocifensive behavioral and immunohistochemical analyses in rats. OUM was developed by treating the labial fornix region of the inferior incisors with acetic acid. Linalool at 1% was exposed for 5 min at 30 min before nocifensive behavioral measurements. OUM induced spontaneous pain and mechanical allodynia, which were suppressed by the linalool odor. Mechanical allodynia in the hind paw following the injection of complete Freund's adjuvant was also suppressed by linalool odor. Application of lidocaine to the olfactory bulb attenuated the inhibition of spontaneous pain and hyperactivation of trigeminal spinal nucleus caudalis neurons in OUM model rats. Linalool odor exposure-induced neuronal activation in the locus coeruleus (LC) of OUM model rats was decreased by lidocaine application to the olfactory bulb. The decrease in neuronal activation in the LC was attenuated by the administration of orexin 1 receptor (OX-1) antagonist to the LC. These results suggest that linalool odor stimulation through the olfactory pathway activates LC neurons via OX-1 signaling, leading to the suppression of OUM-induced oral pain.

Ketamine for atypical facial pain and hormonal dysregulation: a case report.

BACKGROUND: Ketamine has garnered increased interest for its promising applications in chronic pain treatment, particularly in cases where conventional therapies have proven insufficient. Nevertheless, despite its potential advantages, ketamine remains classified as a third-line medication for pain management. While there are well-documented reactions to ketamine such as hypertension and tachycardia, not much is known about its relationship to cortisol. In this case report, we explicate the administration of ketamine in a patient presenting with atypical facial pain, examining its multifaceted effects on cortisol levels and concurrent pain management. CASE PRESENTATION: A patient with a history of Cushing's disease underwent multiple resections of a pituitary tumor. Afterwards, the patient began experiencing a burning-like pain on the left side of the face. The discomfort was initially treated with a variety of neuromodulatory and anti-inflammatory medications, which caused intolerable side effects and were not effective for pain. As a final recourse, we initiated a regimen of oral compounded ketamine at 5-10 mg three times daily as needed. The patient exhibited marked amelioration in their pain symptoms; however, there was an elevation in their baseline cortisol. In view of the potential risk of inducing Cushing's syndrome, the administration of daily ketamine was discontinued. CONCLUSION: While ketamine is primarily known to control pain through the antagonization of N-methyl-D-aspartate receptors, its effects on cortisol may also contribute to its analgesic properties. Physicians should be aware of the potential for these interactions, particularly when treating patients with a predisposition to hormonal imbalances.

Photobiomodulation and vitamin B treatment alleviate both thermal and mechanical orofacial pain in rats.

PURPOSE: The present study investigates the efficacy of Photobiomodulation (PBM) and Vitamin B Complex (VBC) to relieve pain, both in separately and combined (PBM and VBC). METHODS: Rats with chronic constriction injury of the right infraorbital nerve (CCI-IoN) or Sham surgery were used. PBM was administered at a wavelength of 904 nm and energy density of 6.23 J/cm2 and VBC (containing B1, B6 and B12) subcutaneously, both separately and combined. Behavioral tests were performed to assess mechanical and thermal hypersensitivity before and after CCI and after PBM, VBC, or PBM + VBC. The expression of inflammatory proteins in the trigeminal ganglion and the immunohistochemical alterations of Periaqueductal Gray (PAG) astrocytes and microglia were examined following CCI and treatments. RESULTS: All testeds treatments reversed the painful behavior. The decrease in pain was accompanied by a decrease of Glial Fibrillary Acidic Protein (GFAP), a specific astrocytic marker, and Ionized calcium-binding adaptor molecule 1 (Iba-1), a marker of microglia, and decreased expression of Transient Receptor Potential Vanilloid 1 (TRPV1), Substance P, and Calcitonin Gene-Related Peptide (CGRP) induced by CCI-IoN in PAG and Trigeminal ganglion. Furthermore, both treatments showed a higher expression of Cannabinoid-type 1 (CB1) receptor in the trigeminal ganglion compared to CCI-IoN rats. Our results show that no difference was observed between groups. CONCLUSION: We showed that PBM or VBC regulates neuroinflammation and reduces inflammatory protein expression. However, the combination of PBM and VBC did not enhance the effectiveness of both therapies alone.

Antinociceptive and anxiolytic-like effects of Lavandula angustifolia essential oil on rat models of orofacial pain.

BACKGROUND: Nociceptive and inflammatory orofacial pain is highly prevalent in the population, which justifies the search for safer analgesics. There is increasing evidence of the analgesic and anxiolytic potential of Lavandula angustifolia essential oil (LAV EO), which may represent, when administered through inhalation, may represent a safer alternative for pain treatment. OBJECTIVE: to evaluate whether LAV EO has antinociceptive effect in the formalin test, and anti-hyperalgesic and anxiolytic-like effects in rats subjected to a model of orofacial postoperative pain. METHODOLOGY: Female Wistar rats were exposed to LAV EO (5%) by inhalation for 30 minutes. After exposure, animals were injected with formalin (2.5%, 50 µL) or saline into the hind paw or upper lip and the number of flinches or facial grooming time, respectively, were evaluated. Likewise, on day 3 after intraoral mucosa incision, the animals were exposed to LAV EO and facial mechanical, and heat hyperalgesia were assessed. The influence of LAV EO inhalation on anxiety-like behavior was assessed in operated rats by testing them on the open field (OF) and elevated plus maze (EPM). RESULTS: LAV EO reduced the phase II of the paw formalin test and both phases of the orofacial formalin test. On day three post-incision, LAV EO reduced heat and mechanical hyperalgesia, from 30 minutes up to three hours, and reduced the anxiety-like behavior in operated rats without causing locomotor deficit. CONCLUSION: LAV EO inhalation results in antinociceptive and anxiolytic-like effects in orofacial pain models, which encourages further studies on LAV EO indications and effectiveness on orofacial pain conditions.

Diagnosis and treatment of intractable idiopathic orofacial pain with attention-deficit/hyperactivity disorder.

Attention-deficit/hyperactivity disorder (ADHD) has been reported to be associated with primary chronic pain syndromes, such as fibromyalgia, migraine, and chronic low back pain. Although idiopathic orofacial pain (IOP) is classified as burning mouth syndrome or persistent idiopathic facial or dentoalveolar pain and as a primary chronic pain, the association between IOP and ADHD has not been investigated. This retrospective cohort study investigated the severity of ADHD symptoms measured using the ADHD scale and the effects of treatment using ADHD drugs and the dopamine system stabilizer aripiprazole. The participants were 25 consecutive patients with refractory IOP referred to a psychiatrist and diagnosed with coexisting ADHD according to the Diagnostic and Statistical Manual of Mental Disorders-5. The ADHD scale scores were higher in patients with intractable IOP than those in the general population. Pharmacotherapy used in this study led to clinically significant improvements in pain, anxiety/depression, and pain catastrophizing. Intractable IOP and ADHD were shown to be associated. In the future, screening and pharmacotherapy for ADHD should be considered in the treatment of intractable IOP.

Chronic pain and continuity of analgesic treatment during the COVID-19 pandemic.

INTRODUCTION: Chronic pain can trigger both physical and mental health complications. During the COVID-19 pandemic, patients with chronic diseases have had reduced access to some medications. OBJECTIVE: To determine the pharmacological management of patients with chronic pain and its continuity during the COVID-19 pandemic. METHODS: This was a retrospective longitudinal study of the continuity of analgesic use in patients with chronic pain between September 1, 2019 and February 28, 2021 based on a drug dispensing database. Survival analysis was performed until the discontinuation of chronic analgesics. RESULTS: A total of 12,701 patients who were being treated for chronic pain were identified. Their median age was 70.3 years, and 74.4% were women. The pain of rheumatological origin was the most frequent etiology (46.1%); the most used medications were nonopioid analgesics (78.9%), pain modulators (24.8%) and opioid analgesics (23.3%). A total of 76.1% of the patients experienced interruptions in their management during the study period. The median time to the first interruption of treatment was 5.0 months (95% CI: 4.8-5.2). Those who were treated for oncological pain experienced a greater number of interruptions in their management. CONCLUSIONS: The pharmacological management of patients with chronic pain is heterogeneous, and this real-world study showed that a high proportion of patients experienced an interruption of pain management during the 12 months following the onset of the COVID-19 pandemic.

Antinociceptive effect of ultra-low dose naltrexone in a pre-clinical model of postoperative orofacial pain.

Painmanagement after oral surgeries is essential to enhance recovery, reduce negative outcomes and improve the experience of the patient. Naltrexone (NTX) is a non-selective opioid receptor antagonist that has been shown to modulate neuro-inflammation when employed in low to ultra-low doses. In addition, ultra-low dose naltrexone (ULDN) has been shown to potentiate opioids' analgesia and to have opioid-sparing effects. Herein it was investigated the effect of ULDN in a model of postoperative orofacial pain in rats, and it was tested the hypothesis that blockade of TLR4-signalling pathway contributes to its antinociceptive effect. Systemic NTX reduced heat hyperalgesia in female rats and heat and mechanical hyperalgesia in male rats after incision surgery. Combined treatment with NTX and morphine, both at ineffective doses, resulted in a significant reduction of heat hyperalgesia in male rats. NTX injection at the incision site failed to change heat hyperalgesia, but injection at the trigeminal ganglion (TG) or subnucleus caudalis (Sp5C) caused a significant reduction in heat hyperalgesia. At these sites, blockade of TLR4 impeded NTX effect. Lipopolysaccharide (LPS) injection in the intraoral mucosa resulted in facial heat hyperalgesia an increase in IL-1ß levels in the TG, which were reduced by systemic NTX. Stimulation of macrophages with LPS resulted in increase of nitric oxide, IL-1ß and CXCL-2 levels which were reduced by NTX. Altogether, these results provide evidence for an antinociceptive effect of ULDN in postoperative orofacial pain and suggest that blockade of TLR4 and downstream signaling pathway contribute to its effect.

Prepontine cisternal routine for intrathecal targeted drug delivery in craniofacial cancer pain treatment: technical note.

Intrathecal targeted drug delivery provides effective relief for cancer-related pain. However, its validation in management of craniofacial pain remains much less widely practiced, mainly due to the localized diffusion of analgesic agent with current approach. Here, we report our experience of prepontine cisternal routine for placement and implantation of intrathecal targeted drug delivery in two cases of cancer-related craniofacial pain. Lumbar cannulation was applied and the intrathecal catheter tip was positioned at the prepontine cistern under fluoroscopic guidance during the surgical implantation. Postoperative imaging confirmed that the catheter tip was successfully placed in the prepontine cisternal space. Satisfactory control of pain was achieved after intrathecal therapy, with significant reduction of background and breakthrough cancer pain. None obvious complications were observed in this study. Thus, our novel intrathecal routine may provide an alternative option for craniofacial pain caused by tumor, who were insufficiently treated by oral analgesic agents.

Antinociceptive effects of bupivacaine and its sulfobutylether-ß-cyclodextrin inclusion complex in orofacial pain.

Bupivacaine hydrochloride (BVC) represents an option to produce long-lasting analgesia, and complexation in cyclodextrins has shown improvements in biopharmaceutical properties. This study aimed to characterize and test the cytotoxicity and antinociceptive effects of BVC complexed in sulfobutylether-ß-cyclodextrin (SBEßCD). The kinetics and stoichiometry of complexation and BVC-SBEßCD association constant were evaluated by phase solubility study and Job's plot. Evidence of the BVC-SBEßCD complex formation was obtained from scanning electron microscopy (SEM), infrared spectroscopy (FTIR), and differential scanning calorimetry (DSC). The cytotoxicity was evaluated in keratinocyte (HaCaT) and neuroblastoma (SH-SY5Y). Antinociceptive effects were registered via orofacial pain models: the formalin test, carrageenan-induced hyperalgesia, and postoperative pain (intraoral incision). The complex formation occurred at a 1:1 BVC-SBEßCD molar ratio, with a low association constant (13.2 M-1). SEM, DSC, and FTIR results demonstrated the host-guest interaction. The IC50% values determined in SH-SY5Y were 216 µM and 149 µM for BVC and BVC-SBEßCD, respectively (p < 0.05). There was no difference in HaCaT IC50%. In orofacial pain model, BVC-SBEßCD significantly prolonged antinociceptive effect, in about 2 h, compared to plain BVC. SBEßCD can be used as a drug delivery system for bupivacaine, whereas the complex showed long-lasting analgesic effects.

Assessment of Electromyographic Changes in a Patient with Masseter Hypertrophy and Muscle Pain after Botulinum Injections: A Case Report and 5 Months Follow-up.

AIM: To determine if botulinum injections in masseters could be an option to avoid surgery and prolonged treatment with occlusal splints and/or drugs to care for both painful bruxism and cosmetic improvement in a patient with a square jaw, bruxism, and orofacial pain. BACKGROUND: Masseter muscle hypertrophy (MMH) is a benign, unilateral, or bilateral, painless enlargement in the lower face. It presents as a symmetrical or asymmetrical increase in the masseter muscle. Masseter muscle hypertrophy (MMH) sometimes can be related to bruxism symptoms like muscle and/or temporomandibular joint (TMJ) pain. CASE DESCRIPTION: A 38-year-old woman complained of bilateral pain at palpation in the masseter body. She also complained about esthetics because of the prominent masseter muscle in the face and square face shape. A diagnosis of bruxism-related myalgia was performed, and treatment with botulinum injections into the masseter muscles was opted for. An oral electromyography was performed to detect the electrical muscular activity of masseter muscles over time. CONCLUSION: After a drastic reduction in the mean electrical activity immediately after the botulinum injections, a progressive increase in strength over time was noted, testifying about the decrease in the effect of botulinum over time. The pain disappeared for 5 months after the injections of botulinum. The reduction of the masseter muscle mass led to a softening of the face shape. CLINICAL SIGNIFICANCE: This case report shows that treatment with botulinum can lead, in the short term, to a reduction in orofacial pain due to a decrease in muscle electrical activity.

Cannabis and orofacial pain: a systematic review.

The naturally occurring cannabis plant has played an established role in pain management throughout recorded history. However, in recent years, both natural and synthetic cannabis-based products for medicinal use (CBPM) have gained increasing worldwide attention due to growing evidence supporting their use in alleviating chronic inflammatory and neuropathic pain associated with an array of conditions. In view of these products' growing popularity in both the medical and commercial fields, we carried out a systematic review to ascertain the effects of cannabis and its synthetically derived products on orofacial pain and inflammation. The application of topical dermal cannabidiol formulation has shown positive findings such as reducing pain and improving muscle function in patients suffering from myofascial pain. Conversely, two orally-administered synthetic cannabinoid receptor agonists (AZD1940 and GW842166) failed to demonstrate significant analgesic effects following surgical third molar removal. There is a paucity of literature pertaining to the effects of cannabis-based products in the orofacial region; however, there is a wealth of high-quality evidence supporting their use for treating chronic nociceptive and neuropathic pain conditions in other areas. Further research is warranted to explore and substantiate the therapeutic role of CBPMs in the context of orofacial pain and inflammation. As evidence supporting their use expands, healthcare professionals should pay close attention to outcomes and changes to legislation that may impact and potentially benefit their patients.

Pharmacologic Management of Neuropathic Pain.

This article aims to provide the practitioner with therapeutic options to treat a broad spectrum of acute and chronic orofacial pain syndromes. The focus will be nonsurgical that the oral health care physician can implement to treat this population of patients. The World Health Organization estimated that more than 1 in every 3 people suffers from acute or chronic pain. This article is primarily devoted to medication management once the diagnosis of neuropathic pain, a true trigeminal neuralgia, or a variant of trigeminal neuralgia often referred to as traumatic neuropathic pain or traumatic trigeminal neuralgia.

Cannabis. Usos y aplicaciones en la práctica odontológica diaria: revisión de la literatura / Cannabis. Uses and applications in daily dental practice: a review of the literature

La evidencia científica presente en la literatura indica que el cannabis puede ser utilizado con fines terapéuticos para tratar distintas afecciones odontológicas. Dado el acceso sencillo a la cavidad bucal, las distintas formulaciones de cannabis pueden aplicarse de forma tópica. La aplicación local de dosis bajas de cannabis ha demostrado alta efectividad para tratar distintas afecciones bucales, constituyendo un tratamiento seguro con baja probabilidad de generar repercusiones sistémicas indeseadas. En la actualidad, está siendo incorporado a materiales convencionales de uso e higiene odontológica con la finalidad de aprovechar sus efectos terapéuticos. El cannabis tiene múltiples usos en odontología: como componen-te de enjuagues bucales y soluciones para la desinfección de conductos radiculares, en tratamientos de trastornos de ansiedad bucal, como complemento en terapias oncológicas, como analgésico para atenuar el dolor inflamatorio y el neuropático, como miorrelajante y condroprotector para tratar trastornos de articulación témporomandibular (ATM) y bruxismo, como osteomodulador para el tratamiento de patologías que comprometen la integridad ósea, como la enfermedad periodontal y la osteoporosis, y para la cicatrización ósea asociada a fracturas, extracciones dentarias e implantes, y como inmunomodulador con potencial terapéutico para tratar patologías autoinmunes como las enfermedades reumáticas. El trata-miento local con cannabis es efectivo, bien tolerado por el paciente y con pocos efectos adversos. Por lo tanto, se puede concluir que el cannabis aporta un enorme abanico de posibilidades terapéuticas para tratar distintas afecciones odontológicas, aunque aún se requiere mayor cantidad de estudios científicos que avalen su utilización en cada situación fisiopatológica particular (AU)

The scientific evidence present in the literature indicates that cannabis can be used for therapeutic purposes to treat different dental conditions. Given the easy access to the oral cavity, the different cannabis formulations can be applied topically. The local application of low doses of cannabis has shown high effectiveness in treating different oral conditions, constituting a safe treatment with a low probability of generating unwanted systemic repercussions. It is currently being incorporated into conventional materials for dental use and hygiene in order to take advantage of its therapeutic effects. Cannabis has multiple uses in dentistry: as a component of mouthwashes and solutions for disinfecting root canals, in the treatment of oral anxiety disorders, as a complement in oncological therapies, as an analgesic to reduce inflammatory and neuropathic pain, as a muscle relaxant and chondroprotective to treat temporomandibular joint disorders and bruxism, as an osteomodulator for the treatment of pathologies that compromise bone integrity, such as periodontal disease and osteoporosis, and or bone healing associated with fractures, dental extractions and implants, and as immunomodulator with therapeutic potential to treat autoimmune pathologies such as rheumatic diseases. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Local treatment with cannabis is effective, well tolerated by the patient and with few adverse effects. Therefore, it can be concluded that cannabis provides an enormous range of therapeutic possibilities to treat different dental conditions, although more scientific studies are still required to support its use in each particular pathophysiological situation (AU)

Anti-nociceptive efficacy of essential oil-based extracts for the management of orofacial pain: a systematic review of available evidence.

OBJECTIVE: Experimental studies have shown that essential oil (EO)-based extracts derived from medicinal plants exhibit antinociceptive activity. The aim of the present systematic review was to assess the anti-nociceptive efficacy of EO-based extracts for the management of orofacial pain (OFP). MATERIALS AND METHODS: To address the focused question "Are EO-based formulations effective for the management of OFP disorders?", indexed databases were searched without time and language restrictions using the preferred reporting items for systematic reviews and meta-analysis guidelines. Risk of bias (ROB) was assessed. RESULTS: Eight studies were included and processed for data extraction. Two studies were clinical (one in adults and one in children) and 6 were performed in rodents. Results from one clinical study showed that inhalation of EO-extracts does not affect subjective toothache scores; and results from the study on children reported that inhalation of lavender oil reduces anxiety and pain during and after tooth extraction. Results from all experimental studies showed that administration of EO-extracts reduces orofacial nociceptive behavior. The ROB was high in 50% and 83.3% of the clinical and experimental studies, respectively. CONCLUSIONS: The anti-nociceptive efficacy of EO-extracts for the management of OFP remains debatable. Further well-designed and power-adjusted randomized clinical trials are needed in this regard.

Modulation of excitatory synaptic transmissions by TRPV1 in the spinal trigeminal subnucleus caudalis neurons of neuropathic pain rats.

The present study examined contribution of the transient receptor potential vanilloid 1 channel (TRPV1) to the chronic orofacial pain. Bilateral partial nerve ligation (PNL) of the mental nerve, a branch of trigeminal nerve, was performed to induce neuropathic pain. The withdrawal threshold in response to mechanical stimulation of the lower lip skin was substantially reduced after the surgery in the PNL rats while it remained unchanged in the sham rats. This reduction in the PNL rats was alleviated by pregabalin injected intraperitoneally (10 mg/kg) and intracisternally (10, 30, 100 µg). Furthermore, an intracisternal injection of AMG9810, an antagonist of TRPV1, (1.5, 5.0 µg) attenuated the reduction of withdrawal threshold. Spontaneous and miniature excitatory postsynaptic currents (sEPSCs and mEPSCs) were recorded from the spinal trigeminal subnucleus caudalis (Vc) neurons in the brainstem slice, which receive the orofacial nociceptive signals. In the PNL rats, superfusion of capsaicin (0.03, 0.1 µM) enhanced their frequency without effect on the amplitude and the highest concentration (0.3 µM) increased both the frequency and amplitude. In the sham rats, only 0.3 µM capsaicin increased their frequency. Thus, capsaicin-induced facilitation of sEPSCs and mEPSCs in the PNL rats was significantly stronger than that in the sham rats. AMG9810 (0.1 µM) attenuated the capsaicin's effect. Capsaicin was ineffective on the trigeminal tract-evoked EPSCs in the PNL and sham rats. These results suggest that the chronic orofacial pain in the PNL model results from facilitation of the spontaneous excitatory synaptic transmission in the Vc region through TRPV1 at least partly.