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.

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.

Botulinum toxin type A is a potential therapeutic drug for chronic orofacial pain.

BACKGROUND: Botulinum toxin type A (BTX-A), produced by the gram-positive anaerobic bacterium Clostridium botulinum, acts by cleaving synaptosome-associated protein-25 (SNAP-25), an essential component of the presynaptic neuronal membrane that is necessary for fusion with the membrane proteins of neurotransmitter-containing vesicles. Recent studies have highlighted the efficacy of BTX-A in treating chronic pain conditions, including lower back pain, chronic neck pain, neuropathic pain, and trigeminal neuralgia, particularly when patients are unresponsive to traditional painkillers. This review focuses on the analgesic effects of BTX-A in various chronic pain conditions, with a particular emphasis on the orofacial region. HIGHLIGHT: This review focuses on the mechanisms by which BTX-A induces analgesia in patients with inflammatory and temporomandibular joint pain. This review also highlights the fact that BTX-A can effectively manage neuropathic pain and trigeminal neuralgia, which are difficult-to-treat chronic pain conditions. Herein, we present a comprehensive assessment of the central analgesic effects of BTX-A and a discussion of its various applications in clinical dental practice. CONCLUSION: BTX-A is an approved treatment option for various chronic pain conditions. Although there is evidence of axonal transport of BTX-A from peripheral to central endings in motor neurons, the precise mechanism underlying its pain-modulating effects remains unclear. This review discusses the evidence supporting the effectiveness of BTX-A in controlling chronic pain conditions in the orofacial region. BTX-A is a promising therapeutic agent for treating pain conditions that do not respond to conventional analgesics.

Effectiveness and Safety of Flupentixol and Melitracen Tablets for the Treatment of Patients with Persistent Idiopathic Facial Pain: A Retrospective Observational Study.

BACKGROUND: Flupentixol and melitracen are being investigated for their potential effectiveness in managing persistent idiopathic facial pain (PIFP), based on their mechanisms of action as dopamine receptor antagonists and noradrenaline/serotonin reuptake inhibitors, respectively. The efficacy and safety of flupentixol and melitracen (FM) tablets in treating PIFP were retrospectively analyzed at our hospital. OBJECTIVES: The aim of this study is to determine the effectiveness and safety of FM tablets in treating PIFP. STUDY DESIGN: Retrospective unicentric cohort design. SETTING: An academic university hospital. METHODS: A retrospective analysis was conducted on a cohort comprising 128 patients with a definite diagnoses of PIFP who were treated with FM tablets (flupentixol 0.5 mg and melitracen 10 mg tablet, >= 4 tablets/d) from January 2022 through May 2023 at an academic university hospital. Baseline conditions were statistically described, and Numeric Rating Scale (NRS-11) scores of pain levels before and during treatment were collected. Pain relief rates were calculated. Differences in baseline characteristics between responsive and unresponsive patients were evaluated using statistical tests. Additionally, the side effects experienced during treatment were summarized. RESULTS: Among the included 128 patients, 105 (82.0%) patients achieved pain relief (pain NRS-11 score reduction rate >= 50%). The median treatment onset time was 3 (1-7) days. NRS-11 scores of responsive patients at week 2, week 4, week 8, and week 12 were significantly lower than the baseline NRS-11 scores (P < 0.001), regardless of their Hamilton Depression Rating Scale score. Pain duration was the only factor that related to responsiveness (Wilcoxon rank sum test, P < 0.001; logistic regression, P = 0.001). No serious side effects that could affect patients' lives were observed during the first week of treatments. LIMITATIONS: Due to its retrospective nature, this study is limited by its lack of a randomized control. The lack of data on nonresponders who did not achieve significant pain relief hinders assessing overall change and the placebo effects'. Patients previously treated with antidepressants were excluded, making it hard to determine if FM tablets were a better treatment for PIFP. Additionally, the small sample size in a single center may be influenced by chance variation in pain relief. CONCLUSIONS: FM tablets showed its potential in the management of PIFP with considerable efficacy and safety. Early administration of FM tablets after a PIFP diagnosis may result in a high possibility of pain relief.

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.

Use of antidepressants in the treatment of chronic orofacial pain caused by temporomandibular disorders: A randomized controlled clinical trial.

BACKGROUND AND OBJECTIVE: Temporomandibular disorders (TMDs) are a common pathology, associated with pain in the facial territory and with associated psychological disorders, such as anxiety and depression. The aim of this study was to evaluate the efficacy of antidepressants in the treatment of pain associated with TMD. MATERIALS AND METHODS: Sixty four patients suffering from chronic orofacial pain, randomly distributed in 3 groups: control group treated with night splint, group treated with 10mg/day of citalopram and group treated with 25mg/day of amitriptyline. Pain intensity was assessed, randomly, by a single blinded evaluator, according to the VAS at baseline and after one, three, six and nine weeks. RESULTS: All groups showed a reduction of pain throughout the period of time evaluated, however, the group treated with amitriptyline showed the best pain reduction results 3.3±1.5, 1.5±1.4 and 0.9±1.3 at 3, 6 and 9 weeks, respectively. CONCLUSIONS: Low doses of amitriptyline appear to be a good therapeutic option in patients with TMDs suffering from chronic orofacial pain.

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.

Blockage of the fractalkine pathway reduces hyperalgesia and prevents morphological glial alterations-Comparison between inflammatory and neuropathic orofacial pain in male rats.

This study aimed to evaluate the effects of inhibitors of the fractalkine pathway in hyperalgesia in inflammatory and neuropathic orofacial pain in male rats and the morphological changes in microglia and satellite glial cells (SGCs). Rats were submitted to zymosan-induced arthritis of the temporomandibular joint or infraorbital nerve constriction, and treated intrathecally with a P2 X7 antagonist, a cathepsin S inhibitor or a p-38 mitogen-activated protein kinase (MAPK) inhibitor. Mechanical hyperalgesia was evaluated 4 and 6 h following arthritis induction or 7 and 14 days following nerve ligation. The expression of the receptor CX3 CR1 , phospho-p-38 MAPK, ionized calcium-binding adapter molecule-1 (Iba-1), and glutamine synthetase and the morphological changes in microglia and SGCs were evaluated by confocal microscopy. In both inflammatory and neuropathic models, untreated animals presented a higher expression of CX3 CR1 and developed hyperalgesia and up-regulation of phospho-p-38 MAPK, which was prevented by all drugs (p < .05). The number of microglial processes endpoints and the total branch length were lower in the untreated animals, but the overall immunolabeling of Iba-1 was altered only in neuropathic rats (p < .05). The mean area of SGCs per neuron was significantly altered only in the inflammatory model (p < .05). All morphological alterations were reverted by modulating the fractalkine pathway (p < .05). In conclusion, the blockage of the fractalkine pathway seemed to be a possible therapeutic strategy for inflammatory and neuropathic orofacial pain, reducing mechanical hyperalgesia by impairing the phosphorylation of p-38 MAPK and reverting morphological alterations in microglia and SGCs.

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.

Pharmacological therapy in the management of temporomandibular disorders and orofacial pain: a systematic review and meta-analysis.

BACKGROUND: Temporomandibular disorders (TMD) are manifested by soreness in the jaw joint area and jaw muscles, clicks or creaks when opening or closing the mouth. All these symptoms can be disabling and occur during chewing and when the patient yawns or speaks. Several classes of drugs are used to treat symptoms. This review aims to assess which drug suits the different signs. METHODS: Pubmed, Web of Science and Lilacs were systematically searched until 01/02/2023. Clinical trials were selected that dealt with drugs used in temporomandibular dysfunction RESULTS: Out of 830 papers, eight studies were included. The Meta-Analysis with Continuous Outcomes with Pre-Calculated Effect Sizes resulted in the rejection that there is intergroup variability (p.0.74). CONCLUSIONS: Treatment of orofacial pain is still a significant challenge for dentistry. We can conclude that there is no drug of first choice in the treatment of temporomandibular pain. However, the clinician must distinguish the type of pain and the aetioloic cause of the pain so that the patient can be treated and managed pharmacologically.

Sex differences in descending control of nociception (DCN) responses after chronic orofacial pain induction in rats and the contribution of kappa opioid receptors.

Descending control of nociception (DCN), a measure of efficiency of descending pain inhibition, can be assessed in animals by the combined application of test and conditioning noxious stimuli. Evidence from pre-clinical and clinical studies indicates that this mechanism of pain control may differ between sexes and might be impaired in many chronic pain states. However, little is known about sex differences in DCN efficiency in models of acute and chronic orofacial pain. Herein, we first evaluated DCN responses in male and female rats by the applying formalin into the upper lip or capsaicin into the forepaw as the conditioning stimulus, followed by mechanical stimulation (Randall-Selitto) of the hind paw as the test stimulus. The same protocol (i.e., capsaicin in the forepaw followed by mechanical stimulation of the hind paw) was evaluated in male and female rats on day 3 after intraoral incision and on day 15 and 30 after chronic constriction injury of the infraorbital nerve (CCI-ION). Additionally, we assessed the effect of the kappa opioid receptor (KOR) antagonist Norbinaltorphimine (nor-BNI) on DCN responses of female nerve-injured rats. This study shows that naïve female rats exhibit less efficient DCN compared to males. Postoperative pain did not alter DCN responses in female and male rats, but CCI-ION induced loss of DCN responses in females but not in males. Systemic pretreatment with nor-BNI prevented the loss of DCN induced by CCI-ION in female rats. The results reveal sex differences in DCN responses and female-specific impairment of DCN following chronic orofacial pain. Moreover, the findings suggest that, at least for females, blocking KOR could be a promising therapeutic approach to prevent maladaptive changes in chronic orofacial pain.

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.

Effect of botulinum toxin type A on muscular temporomandibular disorder: A systematic review and meta-analysis of randomized controlled trials.

BACKGROUND: Botulinum toxin type A (BTX-A) is increasingly used to manage painful temporomandibular disorders (TMD). However, the effect of BTX-A on muscular TMD remains unclear. OBJECTIVE: To assess the efficacy, safety and optimal dose of BTX-A for treating TMD. METHODS: We conducted systematic literature searches in MEDLINE, Embase, Web of Science, ClinicalTrials.gov and Cochrane Library until March 2023. We extracted data from randomized controlled trials (RCTs) that evaluated the efficacy and safety of BTX-A in treating muscular TMD. We performed a meta-analysis using a random-effects model. RESULTS: Fifteen RCTs involving 504 participants met the inclusion criteria. BTX-A was significantly more effective than placebo in reducing pain intensity, as measured on a 0-10 scale, at 1 month (MD [95% CI] = -1.92 [-2.87, -0.98], p < .0001) and 6 months (MD [95% CI] -2.08, [-3.19 to -0.98]; p = .0002). A higher dosage of BTX-A (60-100 U bilaterally) was associated with a greater reduction in pain at 6 months (MD [95% CI] = -2.98 [-3.52, -2.44]; p < .001). BTX-A also resulted in decreased masseter muscle intensity (µV) (MD [95% CI] = -44.43 [-71.33, -17.53]; p = .001) at 1 month and occlusal force (kg) at 3 months (MD [95% CI] = -30.29 [-48.22 to -12.37]; p = .0009). There was no significant difference in adverse events between BTX-A and placebo. CONCLUSIONS: BTX-A is a safe and effective treatment for reducing pain and improving temporomandibular muscle and joint function in muscular TMD patients. A bilateral dose of 60-100 U might be an optimal choice for treating muscular TMD pain.

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.

Botulinum toxin type a antinociceptive activity in trigeminal regions involves central transcytosis.

OBJECTIVE: Botulinum toxin type A (BoNT-A) provides lasting pain relief in patients with craniofacial pain conditions but the mechanisms of its antinociceptive activity remain unclear. Preclinical research revealed toxin axonal transport to the central afferent terminals, but it is unknown if its central effects involve transsynaptic traffic to the higher-order synapses. To answer this, we examined the contribution of central BoNT-A transcytosis to its action in experimental orofacial pain. MATERIAL AND METHODS: Male Wistar rats, 3-4 months old, were injected with BoNT-A (7 U/kg) unilaterally into the vibrissal pad. To investigate the possible contribution of toxin's transcytosis, BoNT-A-neutralizing antiserum (5 IU) was applied intracisternally. Antinocicepive BoNT-A action was assessed by duration of nocifensive behaviors and c-Fos activation in the trigeminal nucleus caudalis (TNC) following bilateral or unilateral formalin (2.5%) application into the vibrissal pad. Additionally, cleaved synaptosomal-associated protein of 25 kDa (cl-SNAP-25) immunoreactivity was analyzed in the bilateral TNC. RESULTS: Unilaterally injected BoNT-A reduced the nocifensive behaviors and bilateral c-Fos activation induced by formalin, which was accompanied by the toxin's enzymatic activity on both sides of the TNC. BoNT-A antinociceptive or enzymatic activities were prevented by the specific neutralizing antitoxin. BoNT-A contralateral action occurred independently from ipsilateral side nociception or contralateral trigeminal nerve-mediated axonal traffic. CONCLUSION: Herein, we demonstrate that antinociceptive action of pericranially administered BoNT-A involves transsynaptic transport to second order synapses and contralateral trigeminal nociceptive nuclei. These results reveal more complex central toxin activity, necessary to explain its clinical effectiveness in the trigeminal region-related pain states.

The Therapeutic Effect of Botulinum Toxin Type A on Trigeminal Neuralgia: Are There Any Differences between Type 1 versus Type 2 Trigeminal Neuralgia?

BACKGROUND: Botulinum toxin type A is an effective treatment for trigeminal neuralgia. Moreover, its efficacy in type 2 trigeminal neuralgia and comparative studies between type 1 and type 2 trigeminal neuralgia (TN) still need to be improved. METHODS: We treated 40 TN patients with onabotulinumtoxinA; 18 had type 1 TN, and 22 had type 2 TN. We compared the baseline pain score with the Visual Analogue Scale (VAS) and paroxysm frequency (number per week) at the baseline with those obtained at 1-month and 3-month follow-ups. Nonetheless, we compared the baseline Penn Facial Pain Scale with the scores obtained at the 1-month follow-up. RESULTS: BoNT/A effectively reduced pain intensity and frequency at the 1-month and 3-month follow-ups. Moreover, the type 1 TN and type 2 TN groups had baseline pain scores of 7.8 ± 1.65 and 8.4 ± 1.1, respectively. Pain significantly improved (p < 0.001) in both groups to 3.1 ± 2.3 (type 1 TN) and 3.5 ± 2.3 (type 2 TN) at the 1-month follow-up and to 3.2 ± 2.5 (type 1 TN) and 3.6 ± 2.5 (type 2 TN) at the 3-month follow-up. There was no difference between the two groups (p 0.345). The baseline paroxysm frequencies (number per week) were 86.7 ± 69.3 and 88.9 ± 62.2 for the type 1 and type 2 TN groups, respectively; they were significantly reduced in both groups at the 1-month and 3-month follow-ups without significant differences between the two groups (p 0.902). The Pain Facial Pain Scale improved at the 1-month follow-up, and no significant differences were found between the two groups. There was a strong correlation between background pain and paroxysm pain intensity (r 0.8, p < 0.001). CONCLUSIONS: Botulinum toxin type A effectively reduced the pain, paroxysm frequency, and PFPS scores of type 1 and type 2 trigeminal neuralgia patients without statistically significant differences. Facial asymmetry was the only adverse event.

Facial pain associated with vein of Trolard thrombosis Case report Neurology.

Cerebral venous thrombosis is a rare condition, with identified and described risk factors mainly associated with prothrombotic states, with a wide variety of symptomatology based on the site affected, the most common being intracranial hypertensive syndrome, focal or encephalopathy. Cortical veins of the superficial system are among the least frequently affected veins. The following describes a case of painful facial symptoms progressing to a focal syndrome associated with a history of chronic oral contraceptive use, with thrombosis of vein of Trolard detected and successfully treated with oral anticoagulants.

Is Botulinum Toxin Effective in Treating Orofacial Neuropathic Pain Disorders? A Systematic Review.

BACKGROUND: The aim of this paper is to provide a systematic review of the literature regarding the clinical use of botulinum toxin (BTX) to treat various orofacial neuropathic pain disorders (NP). METHODS: A comprehensive literature search was conducted using Medline, Web of Science, and the Cochrane Library databases. Only randomized clinical trials (RCT) published between 2003 and the end of June 2023, investigating the use of BTX to treat NP, were selected. PICO guidelines were used to select and tabulate the articles. RESULTS: A total of 6 RCTs were selected. Five articles used BTX injections to treat classical trigeminal neuralgia, and one to treat post-herpetic neuralgia. A total of 795 patients received BTX injections. The selected studies utilised different doses and methods of injections and doses. All the selected studies concluded superiority of BTX injections over placebo for reducing pain levels, and 5 out 6 of them highlighted an improvement in the patient's quality of life. Most of the studies reported transient and mild side effects. CONCLUSION: There is evidence of the efficacy of BTX injections in orofacial pain management. However, improved study protocols are required to provide direction for the clinical use of BTX to treat various orofacial neuropathic pain disorders.