瞬时感受器电位离子通道蛋白A1及其参与口颌面疼痛的研究进展

疼痛是一种与组织损伤或潜在组织损伤相关的不愉快的主观感觉和情感体验。目前,包括颞下颌关节疼痛及偏头痛在内的口颌面疼痛的发病机制尚未完全清楚。在疼痛过程中发挥作用的细胞因子较多,瞬时感受器电位离子通道蛋白 （ transient receptor potential ion channel protein, TRPs）是一类非选择性阳离子通道蛋白家族,近年研究发现,该蛋白家族亚族TRPA中的成员TRPA1与痛觉的产生关系密切。现就TRPA1及其参与口颌面疼痛的研究进展做一综述。     

三叉神经脊束核小胶质细胞在大鼠口面部癌性疼痛调节过程中的作用评价

目的 探讨三叉神经脊束核尾侧亚核（Vc）小胶质细胞在口腔癌性疼痛调控中的作用。方法 健康成年雄性Wistar大鼠（280~300 g）,采用舌黏膜下注射Walker 256细胞悬液,制备舌肿瘤疼痛模型。实验一,将大鼠随机分为2组（n=10）,即对照组（Sham组）和肿瘤组（Tumor组）。观察肿瘤生长,通过测定大鼠机械缩头反应阈值（HWMT）观察口面部机械痛行为,通过免疫荧光技术检测Vc小胶质细胞的增殖、活化情况。实验二,将大鼠随机分为4组（n=10）,即对照+空白组（Sham+Veh组）、对照+抑制剂组（Sham+Mino组）、肿瘤+空白组（Tumor+Veh组）、肿瘤+抑制剂组（Tumor+Mino组）。检测Vc小胶质细胞的增殖、活化情况,利用qRT-PCR检测Vc中Iba-1、IL-6、IL-1β及TNF-α的mRNA表达水平。测定HWMT,观察大鼠口面部机械痛行为变化。采用SPSS 19.0 软件包对数据进行统计学处理。结果 与Sham组相比,随着肿瘤不断增长,Tumor组于第5天时开始出现口面部机械痛（P<0.05）,Vc小胶质细胞显著增殖、活化,直至第10天仍处于口面部机械痛敏和小胶质细胞活化状态。给予米诺环素后,与Tumor+Veh组相比,Tumor+Mino组大鼠的Vc小胶质细胞增殖活化显著受到抑制,Iba-1、IL-6、IL-1β及TNF-α mRNA水平显著降低（P<0.01）,HWMT显著升高（P<0.05）,机械痛敏显著减轻。结论 小胶质细胞增殖活化促进炎症因子释放,参与口面部癌性疼痛的发生、发展过程。抑制小胶质细胞活化,可显著减轻口面部癌性疼痛。     

三叉神经脊束核在口面痛传导中的作用

三叉神经脊束核位于延髓段，延髓的外侧及三叉神经脊束的内侧，解剖学上证实三叉神经脊束核是口腔颌面部信息向中枢传导的第一门户，目前认为三叉神经脊束核尾侧亚核及相邻区域是参与口面部伤害信息传导的重要部位，机体内许多神经生化物质包括P物质，降钙素基因相关肽，阿片肽及肽类，乙酰胆碱，单胺类，氨基酸类等物质参与三叉神经脊束核区域口面部伤害信息的传递过程。     

心源性口面部疼痛2例报告

<正> 冠心病患者的心绞痛,放射至颌面部较为少见,1953年 Bonicd.J.J 报道8%的心绞痛病人的疼痛放射至颌面部,其后1981年 A.Tzukertet 报道3例心源性口面部痛。国内尚未见类似报道,现将我院2例心绞痛病人放射到口面部报道如下:     

颞下颌关节区炎性疼痛时受体改变的研究进展

受体的激活在痛觉过敏以及异常痛的产生和维持中发挥着重要的作用，许多研究人员指出颞下颌关节区的炎症会引起三叉神经有关受体改变，相应感觉神经元的兴奋性也发生改变，因此引起患者颌面部疼痛。近年来很多学者针对炎性疼痛时三叉神经相关受体做了大量研究，其中主要包括NMDA受体、NK1受体、P2X受体、辣椒素受体等。     

健康人群的颌面部定量感觉研究

目的 探讨中国人群三叉神经和躯干神经的定量感觉在部位、年龄及性别之间的差异。方法 选择青年组和中年组健康志愿者各20例,在手背、舌尖、下唇及左右颏部分别测量冷/热感觉阈值（CDT/WDT）、冷/热疼痛阈值(CPT/HPT)、机械感觉阈值(MDT)和机械疼痛阈值(MPT),采用重复设计的方差分析进行数据分析。结果 三叉神经分布区域的温度和机械敏感性比手背皮肤高,颏部皮肤的温度敏感性比口内黏膜高;青年组比中年组对温度感觉刺激和机械刺激更为敏感,差异有统计学意义;女性对温度疼痛刺激更为敏感,差异有统计学意义。结论 温度和机械定量感觉测试的应用可以更好的理解不同感觉表型背后的机制,并且为对中国人群三叉神经区域感觉异常方面的研究提供一些基本信息。     

肉芽肿性唇炎1例

1临床资料 患者,女,15岁。10年前下、上唇先后出现反复肿胀,初期肿胀可消退,近2年来唇肿持续不退,上唇重于下唇,并伴发面部肿胀,患者无自觉疼痛、无瘙痒感。该患者曾在外院多次抗炎治疗效果不佳,其母亲右腿有“象皮肿”病史。口面部检查：上、下唇弥漫性肿胀,上唇偏左侧肿胀尤为明显,成瓦楞状,下唇内侧黏膜可见多个散在的“小米粒”大小半透明结节,面部中1／3肿胀,     

鞘内注射阿霉素后离断三叉神经治疗带状疱疹后疼痛

目的观察阿霉素对三叉神经分布区带状疱疹后疼痛(PHN)的镇痛效果。方法对24患者用1%阿霉素直接注射至PHN相应分支的神经干,观察皮肤症状和异常性疼痛,于术后3d、7d、3个月进行评价。结果术后取得了95.8%的疗效,术后3d有效17例,缓解5例,无改善1例;术后7d有效23例,无效1例;术后3月有效23例,无效病例失访。有效病例在3～24个月内均无复发。结论阿霉素神经鞘内注射后,能有效的消除三叉神经分布区PHN,近期疗效较好。     

Frankel Ⅱ结合口面部肌功能矫治替牙期安氏Ⅱ1错(牙合)畸形的临床初探

目的:研究Frankel Ⅱ功能矫治器结合口面部肌功能治疗学对于替牙期安氏Ⅱ¹类错(牙合)畸形患者颅颌面软硬组织的影响。方法:选择2019年7月～2021年7月于我科就诊的25例安氏Ⅱ¹错(牙合)畸形患者,采用Frankel Ⅱ功能矫治器结合口面部肌功能治疗,通过头影测量及口面部肌功能评估计分表,比较治疗前后颌面软硬组织及口面部肌功能的改变。结果:治疗后下颌矢状向生长明显增加;前牙覆盖明显减小,上切牙唇倾度显著减小;口面肌功能明显增强,差异有统计学意义(P<0.05)。结论:Frankel Ⅱ功能矫治器结合口面部肌功能治疗可有效改善替牙期安氏Ⅱ¹类错(牙合)畸形儿童面部形态,不良骨骼生长型,增强口面部肌力。     

过度张口引起口顺痛的作用机制研究

目的:深入研究过度张口引起口面痛的作用机制.方法:观察过度张口动物模型TMJ和咀嚼肌的组织病理改变及SP和PGE2、PGF2α的免疫反应;检测24名健康志愿者过度张口前后口面部的痛阈变化.结果: 过度张口引起了TMJ和咀嚼肌的损伤,损伤局部有SP和PGE2、PGF2α的明显聚积;过度张口后口面部的痛阈明显下降,24-48小时后痛阈基本恢复同前;对过度张口的反应存在个体差异和部位差异.结论:过度张口可损伤TMJ和咀嚼肌,引起口面部疼痛,此过程有内源性致痛物质的参与.     

NGF up-regulates TRPA1: implications for orofacial pain

The transient receptor potential ankyrin repeat 1 (TRPA1) channel is believed to be involved in many forms of acute and chronic hyperalgesia. Nerve Growth Factor (NGF) regulates chronic inflammatory hyperalgesia by controlling gene expression in sensory neurons, including genes involved in inflammatory hyperalgesia in the dental pulp. We hypothesized that NGF increases functional activities of the TRPA1 channel in trigeminal ganglion neurons. Here, we show that NGF induced a concentration- and time-dependent up-regulation of TRPA1 mRNA in trigeminal ganglia neurons, as detected by real-time RT-PCR and in situ hybridization. In addition, NGF evoked a time-dependent increase of mustard oil (MO)-evoked TRPA1 activation in trigeminal ganglia neurons. Collectively, these findings demonstrate that NGF participates in the functional up-regulation of TRPA1 in trigeminal ganglia neurons. These enhanced activities of TRPA1 could play an important role in the development of hyperalgesia following nerve injury and inflammation in the orofacial region.     

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??Pain is an unpleasant subjective feeling and emotional experience related to tissue damage or potential tissue injury. So far?? the etiology and pathogenesis of orofacial pain is not totally clear??which included temoporomandibular joint pain and migraine. Many cytokines play roles in pain. Transient receptor potential ion channel protein is a class of non-selective cation channel protein superfamily. Recent studies have indicated that transient receptor potential ankyrin1 ??TRPA1?? is closely related to pain. This was a review of the study on TAPA1 involved in orofacial pain.     

Identifying genetic and environmental risk factors for chronic orofacial pain syndromes: human models

Chronic orofacial pain syndromes are produced by nerve injury, diseases, and toxins. They constitute an unsolved medical problem because they affect a considerable number of adults and are difficult to treat. There is a remarkable variability among adults in terms of susceptibility to chronic orofacial pain and its characteristics, which suggests that these syndromes are complex heritable traits controlled by alleles of certain polymorphic genes that interact with the environment. Each syndrome is assumed to be determined by a unique set of genes. In the present report, a practical study design is proposed to identify the genes responsible for interindividual variability in orofacial pain levels. This design is based on research strategies that have been used for studying other human diseases as well as pain syndromes outside the orofacial region. Specifically, this design has been used successfully by the authors and others over the past 8 years to study chronic pain syndromes such as migraines, radiculopathy, amputation pain, and postmastectomy pain. The strategies used to study these topics have been adapted to address the unique problems of orofacial pain. The authors believe that the study of genetics provides a novel research approach from which to identify targets for the development of individually tailored approaches in orofacial pain medicine, such as diagnostic and prognostic kits and novel drugs that would prevent pain chronicity in susceptible individuals or alleviate it once it had developed. This report focuses on human models. A follow-up report is intended to extend this design into animal models of orofacial pain syndromes.     

The trigeminal nerve. Part III: The maxillary division

The maxillary nerve gives sensory innervation to all structures in and around the maxillary bone and the midfacial region including the skin of the midfacial regions, the lower eyelid, side of nose, and upper lip; the mucous membrane of the nasopharynx, maxillary sinus, soft palate, palatine tonsil, roof of the mouth, the maxillary gingivae, and maxillary teeth. This vast and complex division of the trigeminal nerve is intimately associated with many sources of orofacial pain, often mimicking maxillary sinus and/or temporomandibular joint involvement. For those who choose to treat patients suffering with orofacial pain and temporomandibular disorders, knowledge of this nerve must be second nature. Just providing the difficult services of a general dental practice should be stimulus enough to understand this trigeminal division, but if one hopes to correctly diagnose and treat orofacial pain disorders, dedication to understanding this nerve cannot be overstated. In this, the third of a four part series of articles concerning the trigeminal nerve, the second or maxillary division will be described and discussed in detail.     

Proposal for a standardized protocol for the systematic orofacial examination of patients with Hereditary Sensory Radicular Neuropathy

AIM: To apply a standardized protocol for the orofacial evaluation of two adult siblings (one male and one female) with Hereditary Sensory Radicular Neuropathy (HSRN) that presented with dental problems. SUMMARY: The systematic evaluation consisted of (a) clinical questionnaire; (b) radiographs [orthopantomography and computarized tomography (CT)]; (c) orofacial psychophysical tests (pain, thermal, mechanical and electrical sensation); and (d) histology of gingiva and pulp (optical and transmission electronic microscopy). The female patient had complete insensitivity to orofacial pain and partial facial heat sensitivity, and received dental treatment without anaesthesia or pain. She had a severe and painless jaw infection due to pulp necrosis in tooth 37. The male patient had partial insensitivity to orofacial pain and required anaesthesia for dental treatment. Histological examination of gingivae and pulpal tissue revealed an altered proportion of unmyelinated and myelinated sensory nerve fibres. KEY LEARNING POINTS: * Patients with HSRN may present with significant, silent dental disease. * A standard protocol is helpful when evaluating such patients. * If the opportunity arises, evaluation of pulp tissue may reveal an altered proportion of myelinated and unmyelinated nerve fibres. This may avoid the more estabilished sural nerve biopsy.     

Orofacial pain emerging as a dental specialty

The emerging field of orofacial pain was considered by the American Dental Association for full status as a new dental specialty. While the recognition of orofacial pain as a specialty was denied, the American Academy of Orofacial Pain plans to continue its efforts. Many recent advances in the neuroscience of orofacial pain have led to treatments that provide significant relief for patients with chronic orofacial pain disorders. However, access to this care has been limited, leaving many patients to suffer. Dentists are generally supportive of the efforts to develop oral pain treatment into a specialty because the field will provide benefits for both dentists and their patients. A recent survey of 805 individuals who reported having a persistent pain disorder revealed that more than four out of 10 people have yet to find adequate relief, saying their pain is out of control--despite having the pain for more than five years and switching doctors at least once. "This survey suggests that there are millions of people living with severe uncontrolled pain," says Russell Portenoy, MD, president of the American Pain Society. "This is a great tragedy. Although not everyone can be helped, it is likely that most of these patients could benefit if provided with state-of-the-art therapies and improved access to pain specialists when needed." Development of the field of orofacial pain into a dental specialty has been moved primarily by the fact that historically, patients with complex chronic orofacial pain disorders have not been treated well by any discipline of healthcare. Recent studies of chronic orofacial pain patients have found that these patients have a higher number of previous clinicians and have endured many years with pain prior to seeing an orofacial pain dentist (see Figure 1). Complex pain patients and the clinicians who see them are often confused about who they should consult for relief of the pain. Treatment for those patients within the existing structure of dental or medical specialties has been inadequate, with millions of patients left suffering. Insurers are also confused with regard to reimbursement and may make decisions to exclude treatment for orofacial pain disorders under both dental and medical policies. However, dentistry has taken a leading role in healthcare to address the national problem of developing the field of orofacial pain into a dental specialty. A study of dentists and dental specialists has shown that there is a recognized need and broad support for developing this field into a specialty.     

Clinical neurophysiology and quantitative sensory testing in the investigation of orofacial pain and sensory function

Chronic orofacial pain represents a diagnostic and treatment challenge for the clinician. Some conditions, such as atypical facial pain, still lack proper diagnostic criteria, and their etiology is not known. The recent development of neurophysiological methods and quantitative sensory testing for the examination of the trigeminal somatosensory system offers several tools for diagnostic and etiological investigation of orofacial pain. This review presents some of these techniques and the results of their application in studies on orofacial pain and sensory dysfunction. Clinical neurophysiological investigation has greater diagnostic accuracy and sensitivity than clinical examination in the detection of the neurogenic abnormalities of either peripheral or central origin that may underlie symptoms of orofacial pain and sensory dysfunction. Neurophysiological testing may also reveal trigeminal pathology when magnetic resonance imaging has failed to detect it, so these methods should be considered complementary to each other in the investigation of orofacial pain patients. The blink reflex, corneal reflex, jaw jerk, sensory neurography of the inferior alveolar nerve, and the recording of trigeminal somatosensory-evoked potentials with near-nerve stimulation have all proved to be sensitive and reliable in the detection of dysfunction of the myelinated sensory fibers of the trigeminal nerve or its central connections within the brainstem. With appropriately small thermodes, thermal quantitative sensory testing is useful for the detection of trigeminal small-fiber dysfunction (Adelta and C). In neuropathic conditions, it is most sensitive to lesions causing axonal injury. By combining different techniques for investigation of the trigeminal system, an accurate topographical diagnosis and profile of sensory fiber pathology can be determined. Neurophysiological and quantitative sensory tests have already highlighted some similarities among various orofacial pain conditions and have shown heterogeneity within clinical diagnostic categories. With the aid of neurophysiological recordings and quantitative sensory testing, it is possible to approach a mechanism-based classification of orofacial pain.     

TRPA1 contributes to capsaicin‐induced facial cold hyperalgesia in rats

Orofacial cold hyperalgesia is known to cause severe persistent pain in the face following trigeminal nerve injury or inflammation, and transient receptor potential (TRP) vanilloid 1 (TRPV1) and TRP ankylin 1 (TRPA1) are thought to be involved in cold hyperalgesia. However, how these two receptors are involved in cold hyperalgesia is not fully understood. To clarify the mechanisms underlying facial cold hyperalgesia, nocifensive behaviors to cold stimulation, the expression of TRPV1 and TRPA1 in trigeminal ganglion (TG) neurons, and TG neuronal excitability to cold stimulation following facial capsaicin injection were examined in rats. The head‐withdrawal reflex threshold (HWRT) to cold stimulation of the lateral facial skin was significantly decreased following facial capsaicin injection. This reduction of HWRT was significantly recovered following local injection of TRPV1 antagonist as well as TRPA1 antagonist. Approximately 30% of TG neurons innervating the lateral facial skin expressed both TRPV1 and TRPA1, and about 64% of TRPA1‐positive neurons also expressed TRPV1. The TG neuronal excitability to noxious cold stimulation was significantly increased following facial capsaicin injection and this increase was recovered by pretreatment with TRPA1 antagonist. These findings suggest that TRPA1 sensitization via TRPV1 signaling in TG neurons is involved in cold hyperalgesia following facial skin capsaicin injection.     

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.