Neuropathic pain in the orofacial region: clinical and research challenges

Neuropathic pain in the orofacial region poses a difficult challenge to the treating physician. In some cases diagnosis is far from easy. Common causes of orofacial neuropathic pain are reviewed here, with a focus on the 2 most common: postherpetic neuralgia and posttraumatic painful peripheral neuropathy. In addition, the discussion includes idiopathic trigeminal neuralgia (tic douloureux), a neuropathic pain syndrome that is nearly unique to the trigeminal distribution (very rarely, it has also been reported in the glossopharyngeal region). Brief summaries of major research problems and successes are also provided.     

Orofacial pain and sensory disorders in the elderly

Many orofacial pain conditions occur in the elderly. Specifically,this article reviews the prevalence of general and orofacial-related pain in the elderly. The authors also describe and discuss the likely disorders and diseases that produce facial pain and burning pain in the mouth. They do not cover jaw joint pain, oral sores, or ulceration-induced pain, as these conditions are better discussed in the context of arthritis and oral pathologies of the mouth. The authors discuss oral motor disorders, myogenous pain, vascular pain, headaches, trigeminal neuralgia, trigeminal neuropathic dis-ease, postherpetic neuralgia, burning mouth syndrome, and occlusal dysesthesia.     

Differential diagnosis of toothache to prevent erroneous and unnecessary dental treatment

Toothache represents the most common example of oro-facial pain. Its origin is mostly odontogenic, but several other conditions may mimic dental pain or present themselves as such. Well-known examples are myofascial pain, trigeminal neuropathies like neuralgia and painful post-traumatic trigeminal neuropathic pain, oro-facial neurovascular pains, cardiac pain and sinus disease. This review first discusses the current knowledge on the underlying pathophysiology of heterotopic tooth pain. Afterwards, several conditions potentially presenting as toothache will be illustrated regarding clinical features, diagnosis and management.     

Bi-modal radiofrequency treatment for coexisting neuralgia and neuropathy in adjacent divisions of the trigeminal nerve

Trigeminal neuralgia and deafferentation neuropathic pain, or trigeminal neuropathy, are different symptomatologies, rarely reported to present together. The case of a 65-year-old gentleman suffering from trigeminal neuralgia of the maxillary and mandibular division is reported. He first underwent an infraorbital neurectomy that was complicated by deafferentation neuropathic pain, whilst his mandibular neuralgia continued. He was treated successfully for both the neuropathic and neuralgic symptoms in the same session using ultra-extended euthermic pulsed radiofrequency treatment for the maxillary division (V2) and radiofrequency thermocoagulation for the mandibular division (V3). This report is novel in describing the use of dual modalities in the same session for two distinct coexisting clinical entities in two different divisions of the same cranial nerve. The use of ultra-extended pulsed radiofrequency treatment for neuropathic pain in this case is also unique. Nearly 2 years after the procedure, the patient continues to have complete pain relief.     

Management issues of neuropathic trigeminal pain from a dental perspective

Neuropathic trigeminal pain conditions are more common than is generally appreciated. Sites inside the mouth as well as involvement of extraoral tissues are common manifestations of these disorders. There is a general lack of recognition of the complex characteristics of neuropathic trigeminal pain that frequently lead to mischaracterization of the nature of the complaint. Dentists are in an excellent position to detect the presence of neuropathic trigeminal pain and help to provide a rational diagnosis. The high prevalence of orofacial pain of dental origin and the dramatic similarities between neuropathic orofacial pain and odontogenic and other pathologic pains in the region frequently lead to incorrect diagnoses and, more importantly, inappropriate treatments that are frequently invasive and irreversible. The records of patients presenting with neuropathic pain at our university pain clinic were reviewed to gain insight into dental factors as they related to the etiology, presentation, diagnosis, and management of neuropathic pain of the trigeminal system. Relative to etiology, the records review revealed that most onsets were associated with a specific dental treatment or odontogenic symptom that resulted in a dental diagnosis or treatment. Initial treatment modalities that either caused the pain or were used to address painful symptoms commonly included replacement of restorations, endodontic therapy, apicectomy, extraction, splint therapy, and occlusal equilibration. Correct diagnosis, and particularly early definitive diagnosis, of neuropathic trigeminal pain is crucial to avoid invasive and potentially more damaging forms of treatment.     

Spontaneous pain attacks: neuralgic pain

Paroxysmal orofacial pains can cause diagnostic problems, especially when different clinical pictures occur simultaneously. Pain due to pulpitis, for example, may show the same characteristics as pain due to trigeminal neuralgia would. Moreover, the trigger point of trigeminal neuralgia can either be located in a healthy tooth or in the temporomandibular joint. Neuralgic pain is distinguished into trigeminal neuralgia, glossopharyngeal neuralgia, Horton's neuralgia, cluster headache and paroxysmal hemicrania. In 2 cases trigeminal neuralgia is successfully managed with a neurosurgical microvascular decompression procedure according to Jannetta. Characteristic pain attacks resembling neuralgic pain result from well understood pathophysiological mechanisms. Consequently, adequate therapy, such as a Janetta procedure and specific pharmacological therapy, is available.     

Antiepileptic drugs for the treatment of neuropathic pain: A systematic review

Many therapies have been proposed for the management of neuropathic pain, and they include the use of different antiepileptic drugs. However, the lack of high quality studies indicates that results on the different neuropathic disorders under study do not recommend a particular drug treatment. This study makes a systematic review of the published literature on the use of several antiepileptic drugs to treat neuropathic pain, and has the objective of considering both its clinical characteristics and pharmacological use, which will depend on their level of scientific evidence and will follow the principles of evidence-based dentistry. The articles were stratified according to their scientific evidence using the SORT criteria (Strength of Recommendation Taxonomy), and it included those articles that only have level 1 or 2. Randomized clinical trials were stratified according to their level of quality using the JADAD scale, an instrument described by Jadad et al. (7). to assess the quality of clinical trials, while studies with a level below 3 were discarded. Recently, type A or B recommendations are given in favor or against the use of antiepileptic drugs to treat neuropathic pain on the basis of their scientific quality. Key words:Neuropathic pain, antiepileptic drugs (AEDs), trigeminal neuralgia, glossopharyngeal neuralgia, post- herpetic neuralgia, burning mouth syndrome, persistent idiopathic facial pain.     

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疼痛治疗分为药物治疗和非药物治疗。药物治疗包括非甾体类抗炎药、阿司匹林和扑热息痛等非阿片类镇痛药、阿片类镇痛药、"辅助"药物如抗抑郁药阿米替林和抗惊厥药卡马西平等。非药物治疗包括神经刺激疗法、神经阻滞疗法、外科手术、物理治疗、心理-行为疗法等。本文介绍我们临床上常见的颞下颌关节骨关节炎、肌筋膜疼痛、神经病理性疼痛(非典型牙痛、治疗后神经痛、三叉神经痛)及复合性局部疼痛综合征的主要临床用药和理论基础,如非甾体类抗炎药特异性COX-2抑制剂、改善骨关节炎症状和关节结构的药物硫酸氨基葡萄糖、阿片类药物曲马多、三环类抗抑郁药阿米替林、新一代抗惊厥药加巴喷丁等。     

Herpes zoster in HIV infection with osteonecrosis of the jaw and tooth exfoliation

BACKGROUND: Herpes zoster (HZ) infection of the trigeminal nerve is associated with complications such as postherpetic neuralgia, facial scarring, loss of hearing ability and conjunctivitis. Until 2005, postherpetic alveolar necrosis and spontaneous tooth exfoliation have been described in 20 cases unrelated to HIV infection. OBJECTIVE: The aim of this study was to describe HIV infection in patients (two women, two men, average age 30 years) who suffered from HZ attacks to their trigeminal nerves. MAIN OUTCOME MEASURES: None of the patients had received antiherpetic medications or antiretroviral therapy. HIV infection was only diagnosed after the development of HZ. Facial scarring with depigmentation and hyperesthesia (postherpetic neuralgia) was diagnosed in all four patients. Oral findings consisted of spontaneous loss of both maxillary or mandibular teeth. Osteonecrosis of varying extent was also found. Treatment consisted of extractions of teeth and administration of antibiotics and analgesics. Healing of alveolar wounds was unremarkable. CONCLUSION: Complications affecting the alveolar bone and teeth seem to be rare in HIV-infected patients.     

Diagnostic challenges of neuropathic tooth pain

This article presents the clinical characteristics, epidemiology, pathophysiology and treatment of 2 neuropathic conditions: trigeminal neuralgia and atypical odontalgia. A case report highlights the complexities involved in diagnosing neuropathic pain. Neuropathic pain is chronic, diverse in quality, difficult to localize and it occurs in the absence of obvious pathology. To avoid multiple, ineffective dental treatments, general practitioners must be familiar with the signs of nonodontogenic sources of tooth pain.     

Psychophysical assessment of patients with posttraumatic neuropathic trigeminal pain

This article reviews the utility of psychophysical approaches in the assessment of posttraumatic neuropathic trigeminal pain. Methods of quantitative sensory testing are derived from psychophysical principles and provide a widely accepted means for characterizing sensory dysfunction in patients who experience injury to the trigeminal nerve. No published study, however, has sought to compare sensory findings from trigeminal nerve-injured patients who develop neuropathic pain with those from trigeminal nerve-injured patients who remain pain-free. Moreover, sensory testing data from trigeminal nerve-injured patients with pain have been published in only a few reports. As a result, remarkably little is known about sensory factors associated with the development of posttraumatic trigeminal neuralgia. Review of the separate literatures suggests that both trigeminal nerve-injured patients with pain and pain-free trigeminal nerve-injured patients exhibit grossly similar impairments in sensory function. In addition, trigeminal nerve-injured patients with pain may be more likely to report cold allodynia than patients without pain and to exhibit signs of central sensitization such as allodynia to light brushing tactile stimuli and abnormal temporal summation of pain. New studies using state-of-the-art psychophysical methods are needed to search for sensory markers that bear on the development of pain. Moreover, the relationship between psychophysical indices of central sensitization and measures of clinical pain should be addressed to obtain a better understanding of the underlying pathophysiology.     

三叉神经痛周围支撕脱术后复发的原因分析及处理

目的：分析三叉神经周围支撕脱术后复发的原因,并行相应手术治疗,提高手术治愈率。方法：对27例三叉神红痛患者行三叉神经第Ⅱ、Ⅲ支撕脱术后复发的病例,根据疼痛复发部位确定残余神经分支,并采用彻底切断及神经干高位切断的方法再行治疗,随访并评估治疗效果。结果：三叉神经第Ⅱ支术后复发痛19例,多在术后6～12个月复发,其中眶外段神经分支残留痛10例,眶内段神经干撕脱不彻底8例,转为第Ⅲ支神经痛1例。第Ⅲ支术后疼痛8例,颊神经未彻底切断4例,舌神经复发痛2例,下牙槽神经未完全切断2例。结论：三叉神经术后复发痛多因神经及分支切断不彻底,术后易有神经残余。三叉神经痛第Ⅱ支的复发率高于第Ⅲ支,因上颌神经解剖走行复杂,应注意彻底切断。针对复发原因,可采用高位及多分支神经切断术,同时可结合颌骨痛点进行骨腔清除术,以提高治疗效果。     

Atypical odontalgia - pathophysiology and clinical management.

Atypical odontalgia (AO) is a chronic form of dental pain without signs of pathology. Several hypotheses have been put forward regarding the pathophysiology. AO has been proposed to be psychogenic, vascular, neuropathic or idiopathic. The scientific evidence supporting or rejecting these hypotheses are reviewed in this paper. At this time, the best supported hypothesis is that AO is a neuropathic pain condition. Relevant differential diagnoses, such as odontogenic pain, sinusitis, trigeminal neuralgia among others, are presented and the evidence regarding possible management strategies is reviewed. A treatment algorithm for AO is proposed based on the rather scarce scientific evidence available and inspired by a similar treatment algorithm for peripheral neuropathic pain. The proposed strategy involves an interdisciplinary approach including patient education, psychological counselling, topical and systemic medication and, importantly, avoidance of invasive treatments like surgery and endodontics. Two illustrative cases are presented.     

Atypical odontalgia – pathophysiology and clinical management

Summary  Atypical odontalgia (AO) is a chronic form of dental pain without signs of pathology. Several hypotheses have been put forward regarding the pathophysiology. AO has been proposed to be psychogenic, vascular, neuropathic or idiopathic. The scientific evidence supporting or rejecting these hypotheses are reviewed in this paper. At this time, the best supported hypothesis is that AO is a neuropathic pain condition. Relevant differential diagnoses, such as odontogenic pain, sinusitis, trigeminal neuralgia among others, are presented and the evidence regarding possible management strategies is reviewed. A treatment algorithm for AO is proposed based on the rather scarce scientific evidence available and inspired by a similar treatment algorithm for peripheral neuropathic pain. The proposed strategy involves an interdisciplinary approach including patient education, psychological counselling, topical and systemic medication and, importantly, avoidance of invasive treatments like surgery and endodontics. Two illustrative cases are presented.     

Association between paroxysmal trigeminal neuralgia and atypical facial pain

Paroxysmal trigeminal neuralgia and atypical facial pain are both fairly common conditions that produce pain in the face of different character. Trigeminal neuralgia is sharp and shooting, brought on by facial movement, change of temperature and by touching the face at a specific point (the trigger point). Atypical facial pain is dull and unrelenting and its site is ill-defined. Trigeminal neuralgia is generally more common in older people, and affects women slightly more than men, and atypical facial pain generally affects younger people, with women predominating. The pains should never be confused. We have noticed that many patients with trigeminal neuralgia have additional symptoms of atypical facial pain and so we reviewed the records of the Pain Relief Unit retrospectively. Of the 83 patients identified with trigeminal neuralgia where records were adequate, 35 (42%) also had atypical facial pain. Five of these had developed it before the onset of trigeminal neuralgia and could be examples of pretrigeminal neuralgia. There were eight patients in the series with multiple sclerosis, of whom two also had atypical facial pain. There seemed to be no relationship between the development of atypical facial pain and the interventions used to treat trigeminal neuralgia. It is important that both conditions are identified and treated individually.     

大鼠三叉神经病理性疼痛致病关键转录分子分析

目的 ：分析三叉神经病理性疼痛致病关键转录分子,筛选参考三叉神经痛发病的关键分子。方法 ：构建大鼠三叉神经病理性疼痛模型,即眶下神经慢性缩窄环模型（chronic constriction injury of distal infraorbital nerve, IoNCCI）,观察动物行为并收集三叉神经节进行RNA-seq转录组学分析。采用StringTie对基因组表达进行注释和定量,进一步计算基因和转录本的FPKM。使用DESeq2进行组间比较,设置筛选条件为P<0.05和差异倍数（fold change）>2及<0.5,筛选差异基因,采用火山图和聚类图进行展示。应用clusterProfiler软件对差异基因进行GO功能富集分析。结果：术后第5天（POD5）,大鼠抓挠面部行为上升达到峰值;术后第7天（POD7）,von-frey值降到最低,提示大鼠机械痛阈值明显下降。RNA-seq分析IoN-CCI大鼠神经节,发现显著上调的信号通路包括B细胞受体信号通路、细胞黏附、补体及凝血级联通路;显著下调通路为系统性红斑狼疮相关调控通路;Cacna1s、Cox8b、Myl1...     

耳-床线定位射频治疗三叉神经痛术后疗效分析

对48例采用耳-床线定位射频治疗三叉神经痛的患者进行5年的回顾和分析,观察术后疼痛、复发及并发症情况.一次性穿刺成功率100%;经1次治疗疼痛完全消失者46例, 疼痛明显减轻、发作次数明显减少者2例,无复发病例,无穿刺相关并发症发生.通过回顾分析确定穿刺针针尖到耳-床线垂直距离控制在:第Ⅲ支8～10 mm,第Ⅱ支6～7 mm,第Ⅰ支4～5 mm.为避免三叉神经第Ⅰ支损伤,垂直距离控制在6 mm以上而且针尖决不能超过耳-床线.     

Orofacial pain in cancer: part I--mechanisms

The mechanisms involved, and possible treatment targets, in orofacial pain due to cancer are poorly understood. The aim of the first of this two-part series is to review the involved pathophysiological mechanisms and explore their possible roles in the orofacial region. However, there is a lack of relevant research in the trigeminal region, and we have therefore applied data accumulated from experiments on cancer pain mechanisms in rodent spinal models. In the second part, we review the clinical presentation of cancer-associated orofacial pain at various stages: initial diagnosis, during therapy (chemo-, radiotherapy, surgery), and in the post-therapy period. In the present article, we provide a brief outline of trigeminal functional neuro-anatomy and pain-modulatory pathways. Tissue destruction by invasive tumors (or metastases) induces inflammation and nerve damage, with attendant acute pain. In some cases, chronic pain, involving inflammatory and neuropathic mechanisms, may ensue. Distant, painful effects of tumors include paraneoplastic neuropathic syndromes and effects secondary to the release of factors by the tumor (growth factors, cytokines, and enzymes). Additionally, pain is frequent in cancer management protocols (surgery, chemotherapy, and radiotherapy). Understanding the mechanisms involved in cancer-related orofacial pain will enhance patient management.     

阿霉素神经干内注射治疗原发性三叉神经痛285例临床分析

目的:总结作者13年中采用阿霉素神经干内注射治疗原发性三叉神经痛患者285例(339支神经)的经验.方法:对因颌面部出现阵发性剧痛的门诊患者,通过询问病史及临床检查,确诊为原发性三叉神经痛并确定罹患的神经分支后,即行手术,显露其神经束,于束内注入0.5％阿霉素.术后随访观察6个月～13 a,评价疗效.结果:285例患者均于门诊一次完成诊疗,整个过程约lh,所有病例于24～48 h内疼痛停止发作.随访中,有73支分布区出现疼痛复发,复发率约21％,89例出现其他分支疼痛.结论:本组病例证实,阿霉素神经干内注射治疗原发性三叉神经痛疗效确切,无严重并发症.