Unilateral facial injection of Botulinum neurotoxin A attenuates bilateral trigeminal neuropathic pain and anxiety-like behaviors through inhibition of TLR2-mediated neuroinflammation in mice

ObjectivesIn this study, we investigated the possible analgesic effects of Botulinum toxin type A (BoNT/A) on trigeminal neuralgia (TN). A modified TN mouse model was established by chronic constriction injury of the distal infraorbital nerve (dIoN-CCI) in mice, and the possible roles of microglia toll-like receptor 2 (TLR2) and neuroinflammation was investigated.MethodsMale C57BL/6 mice were divided into 3 groups, including sham group, vehicle-treated TN group and BoNT/A-treated TN group. Bilateral mechanical pain hypersensitivity, anxiety-like and depressive-like behaviors were evaluated by using von Frey test, open field, elevated plus-maze testing, and forced swimming test in mice, respectively. The mRNA or protein expression levels of toll-like receptors (TLRs), glia activation markers and proinflammatory factors in the trigeminal nucleus caudalis (TNC) were tested by RT-qPCR, immunofluorescence and Western blotting. We also tested the pain behaviors of TN in Tlr2^−/− mice.ResultsWe found that unilateral subcutaneous injection of BoNT/A into the whisker pad on the ipsilateral side of dIoN-CCI mice significantly attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors induced by dIoN-CCI surgery in mice. The dIoN-CCI surgery significantly up-regulated the expression of TLR2, MyD88, CD11b (a microglia marker), IL-1β, TNF-α and IL-6 in the ipsilateral TNC in mice, and BoNT/A injection significantly inhibited the expression of these factors. Immunostaining results confirmed that BoNT/A injection significantly inhibited the microglia activation in the ipsilateral TNC in dIoN-CCI mice. TLR2 deficiency also alleviated bilateral mechanical pain hypersensitivity and the up-regulation of MyD88 expression in the TNC of dIoN-CCI mice.ConclusionThese results indicate that unilateral injection of BoNT/A attenuated bilateral mechanical pain hypersensitivity and anxiety-like behaviors in dIoN-CCI mice, and the analgesic effects of BoNT/A may be associated with the inhibition of TLR2-mediated neuroinflammation in the TNC.     

Effects of intramural administration of Botulinum Toxin A on gastric emptying and eating capacity in obese patients

BACKGROUND: Intraparietal gastric administration of Botulinum Toxin A has been studied in open trials to induce satiety and increase weight loss of obese patients with contradictory results. In previous studies only the antrum was the target for Botulinum Toxin A, whereas the fundus, which exerts important activity on gastric accommodation, was excluded. In this study we report the effects of injection into both gastric regions on solid gastric capacity and emptying of the stomach. MATERIALS AND METHODS: In this study we extended our previous investigations to include 30 obese patients who received Botulinum Toxin A (120 U into the antrum and 80 U into the fundus) or saline by intraparietal endoscopic injection. The two groups were homogeneous for age, gender, body weight and body mass index. Body weight and body mass index, solid gastric emptying (T(1/2) and T(lag) at the octanoic acid breath test) and maximal gastric capacity for solids (kcal) were determined before injection and 2 months later. The results were expressed as mean values (S.E.M.). t-Test or Wilcoxon test was used for statistical analysis, p<0.05 being considered significant. RESULTS: Both treatments induced a significant reduction of body weight and body mass index but Botulinum Toxin A exerted a significantly greater effect (body weight -11.8+/-0.9 kg vs. -5.5+/-1.1 kg, p<0.0002; body mass index -4.1+/-0.2 vs. -2.2+/-0.4, p<0.001). The maximal gastric capacity for solids was also reduced by both Botulinum Toxin A and placebo, the former being significantly more effective (679+/-114 kcal vs. 237+/-94 kcal, p<0.008). Botulinum Toxin A also significantly increased T(1/2) from 83.4+/-3.9 to 101.6+/-9.9 min, p<0.03) but T(lag) was unchanged. Placebo had no effect on either of these parameters. CONCLUSIONS: Our results demonstrated that Botulinum Toxin A makes weight loss easier in obese patients. It acts by increasing the solid gastric emptying time and reducing the solid eating capacity of the stomach.     

偏侧咀嚼肌痉挛3例报告并文献复习

目的 加强对偏侧咀嚼肌痉挛这一罕见疾病的认识.方法 对我科收治的3例偏侧咀嚼肌痉挛患者的临床资料进行回顾分析,并对相关文献进行复习.结果 3例青年患者,病程长,反复发作性一侧咀嚼肌痉挛,累及咀嚼肌和颞肌,发作时不能张口,病初发作程度较轻,随病程发展,痉挛发作的持续时间及频率加重.诱发痉挛发作的常见因素有咀嚼、咬牙以及说话等.短暂的痉挛通常不伴有肌肉疼痛,严重时可以伴有疼痛.1例患者伴有痉挛侧面部肌肉肥大,2例伴有痉挛侧面部萎缩,无其他神经系统阳性体征.肌电图显示痉挛的咀嚼肌运动单位电位持续发放.2例患者经肉毒毒素局部注射治疗效果显著.结论 对于偏侧咀嚼肌痉挛,肉毒毒素局部注射治疗通常能够获得满意疗效.     

肌电分析在TMD临床疗效评价中的应用

目的:探讨3种不同方法治疗伴有磨牙症TMD的咀嚼肌肌电特征差异,评价3种治疗方法的效果.方法:30例伴有磨牙症的TMD患者被随机分为3组,每组10例.A组进行内毒杆菌毒素A(BTX-A)双侧咬肌肌内注射治疗,B组进行功能训练治疗,C组进行弹性颌垫治疗.对3组研究对象在治疗前、治疗1、3、6个月分别采集双侧咬肌(MM)和颞肌前束(TA)在下颌姿势位(MPP)以及牙尖交错位(ICP)最大紧咬牙时的肌电图(EMG),采用SAS 5.0统计学软件分析比较3组的峰值电位(Amp)之间是否存在统计学差异.结果:横向比较中各个治疗时间段A组患者疼痛视觉模拟评分(VAS)显著低于B组和C组(P＜0.05),肌电显示MPP中A组在治疗过程中能显著降低双侧咬肌肌力(P＜0.05),ICP时A组在1、3个月时显著降低双侧咬肌肌力(P＜0.05),同时双侧颞肌肌力显著增强(P＜0.05).纵向比较中3组在治疗过程中均能明显降低疼痛(P＜0.05),但3组时间点不同,A组缓解疼痛时间较长,肌电图显示3组均可显著降低咬肌MPP肌力(P＜0.05),A、C组可降低ICP咬肌肌力(P＜0.05),A组双侧颞肌肌力可代偿增强(P＜0.05),B、C组颞肌肌力治疗前后均无统计学差异(P＞0.05).结论:临床症状与肌电图的结合使用能够对口颌系统行使功能过程中咀嚼肌的表现进行很好地观测,对TMD患者的咀嚼肌生物力学和结构方面有很好地理解.BTX-A肌内注射方法治疗伴有磨牙症的TMD可显著缓解患者疼痛,疗效持续时间较长.BTX-A肌内注射可显著降低咀嚼肌力,使目标肌肉(咬肌)疲劳得到缓解,促进咀嚼肌力平衡重建,较传统方式存在潜在优势.     

Botulinum Toxin in the Treatment of Muscle Specific Oro-Facial Pain: A Literature Review

Facial pain associated with temporomandibular joint (TMJ) and surrounding structures has been a challenge to clinicians as far as diagnosis and management is concerned. Complexity of anatomical structures within a small area, function of teeth and surrounding periodontal ligament, action of muscles, pathologies, lack of diagnostic investigations, all these complicate specific diagnosis of TMJ disorders. Various classifications have been designed and studied to help diagnose and treat TMJ related disorders, of which the simplest one is pain from TMJ proper and surrounding muscles. Many treatment modalities to treat pain arising from muscles around TMJ like splints, mouth restriction exercises, injection of sclerosing agents etc. have been used with various degrees of success. Botulinum toxin has been shown to be effective in the treatment of oro-facial pain due to muscular disorders and the same is discussed in detail in this review literature.     

The Effect of Intradermal Botulinum Toxin a injections on painful diabetic polyneuropathy

Background and aimsBotulinum toxin type A (BTX-A) have been recently administered to improve Diabetic neuropathies; however, the efficacy of this treatment for relieving pain in painful diabetic polyneuropathy (DPN) has not been studied yet. Herein, we investigated the efficacy of botulinum toxin A (BTX-A) on DPN.MethodsThis prospective, randomized, double-blind, controlled trial was performed in Imam Hossein Medical Center, pain clinic (Tehran, Iran). Diabetic patients (141 cases), between 40 and 70 years old with polyneuropathy in lower limbs were randomly assigned to one of these three groups: 1. Group D1 received 150 units of BTX-A in one foot and normal saline 0.9% in the other foot, 2. Group D2 received BTX-A 150 units in both feet, 3. Group N received normal saline 0.9% in both feet. All injections were performed intradermally using insulin syringes in 20 different points of foot. Visual analogue scale (VAS) and neuropathy pain scale (NPS) were used to compare the groups.ResultsThe improvement of VAS, pain intensity, sharp and hot sensation, sensitive and unpleasant sensation, deep and surface sensation was significant when comparing BTX-A and placebo groups. However, dull and cold sensations improvement (p = 0.114, and p = 0.653; respectively) did not show a significant difference between BTX-A injection and placebo groups. Furthermore, the percentage of changes after treatment indicated that sharp pain was improved more than other complaints (80%, 81%, and 37% for D1, D2, and N groups; respectively).ConclusionIntradermal administration of BTX-A was effective in improving VAS and all of the items of NPS in patients with diabetic polyneuropathy, except for dull and cold sensation.     

Change of Distribution and Timing of Bite Force after Botulinum Toxin Type A Injection Evaluated by a Computerized Occlusion Analysis System

Purpose

The aim of this study was to determine the force distribution and pattern of mastication after injection of botulinum toxin type A (BTX-A) into both masseter muscles. The hypothesis to be tested was that the difference between right and left balance of occlusal force diminishes over time following BTX-A injection.

Materials and Methods

Fifteen patients were submitted to BTX-A injection therapy for subjective masseter hypertrophy. A total of 25 U of BTX-A (50 U in total) was injected into two points located 1 cm apart at the center of the lower one-third of both masseter muscles. All patients were examined using the T-Scan occlusion analysis system before and 4, 8, 12, and 24 weeks after BTX-A injection.

Results

A significant change in force balance was found between the right and left sides over time and the difference between the two sides decreased with the time post-injection, reaching a minimum at 12 weeks. Comparison of the force balance between the anterior and posterior occlusions revealed no significant difference at any of the time points. The occlusion and disclusion times (right and left sides) did not differ significantly with time since BTX-A injection.

Conclusion

A decline in the difference in the clenching force between the left and right sides was found with increasing time up to 12 weeks following BTX-A injection.