原发性三叉神经痛和疱疹后三叉神经痛临床特征及射频热凝术后效果分析

摘要 目的：探讨原发性三叉神经痛（PTN）和疱疹后三叉神经痛（PHN）的临床特征,并比较经卵圆孔射频热凝术（RF-TC）治疗PTN和PHN的临床疗效。方法：随机选取2019年1月至2020年8月在我院治疗的三叉神经痛患者123例,其中原发性三叉神经痛90例,带状疱疹后神经痛33例。所有患者均通过RF-TC进行治疗,治疗后通过视觉模拟量表（VAS）、巴罗神经研究所疼痛强度量表对面部疼痛评分进行疼痛评估,通过巴罗神经研究所麻木评分进行麻木评定,通过健康问卷-9对患者抑郁情况进行评估,通过匹斯堡睡眠质量指数测量患者心理状态。结果：PTN患者发病年龄显著低于PHN患者（P<0.05）,而病程显著高于PHN患者（P<0.05）;PHN患者的眼支发生率高于PTN患者（39.39% vs 8.89%, P<0.05）。两组患者经RF-TC治疗前后VAS评分无显著差异（P>0.05）。PHN组从轻度到重度影响睡眠质量的比例显著高于PTN组（30.30% vs 10.00%, P<0.05）。PTN组患者治疗后中重度抑郁患者比例显著高于PHN组患者（21.11% vs 9.09%, P<0.05）。两组患者经RF-TC治疗后,临床治疗有效率、面麻木程度以及巴罗神经研究所疼痛强度量表评定的面部疼痛无显著差异（P>0.05）。结论：经卵圆孔射频热凝术治疗原发性三叉神经痛和带状疱疹后三叉神经痛是安全有效的,但治疗后疱疹后三叉神经痛失眠的发生率较高,而原发性三叉神经痛的抑郁发生率较高。     

三叉神经痛的临床治疗进展

三叉神经痛是一种常见的面部疼痛性疾病,目前对其病因的认识并不明确。普遍认为压迫可导致三叉神经痛,致病原因包括血管因素和非血管因素,其次创伤也可导致三叉神经痛,常见于口腔外科手术后。三叉神经痛的治疗方法较多,首选药物治疗,包括全身用药和局部用药,药物治疗初期效果明显,但很难治愈三叉神经痛,而且需要长期服药,副作用较大,当药物治疗无效或者患者难以耐受其副作用时,可采用外科疗法进行辅助治疗。三叉神经痛的外科疗法主要包括无创的微血管减压术及有创的射频热凝术、球囊压迫术和甘油毁损术。近年来采用放射外科对三叉神经痛进行治疗,取得了确切效果。此外,还有一些关于其他治疗方法的文献报道,均有一定效果。本文对三叉神经痛病因的认识及临床治疗进展作一回顾性综述。     

Trigeminal neuralgia: a retrospective study of 188 Thai cases

doi: 10.1111/j.1741‐2358.2011.00530.x Trigeminal neuralgia: a retrospective study of 188 Thai cases Objective: To describe the clinical characteristics and treatment of trigeminal neuralgia (TN) in a group of Thai patients. Materials and methods: Records of 188 patients with TN were reviewed retrospectively for patient demographics, the characteristics of the pain and treatment modalities. Results: Of the 188 patients, 37.2% were men and 62.8% were women. The peak incidence (46.8%) was in the age range of 50–69 years. Pain occurred on the right side of the face more often than on the left (1.8:1). The mandibular division of the trigeminal nerve was the most frequently affected (30.3%), followed by the combined maxillary and mandibular divisions (29.3%) and the maxillary division alone (25%). The majority described their attack as a sharp pain (77.6%), and the most common primary locations were at previous extraction sites (40.5%). The most common triggers were chewing (61.2%) and speaking (47.3%). Carbamazepine was the most common prescribed drug (76.1%) for the initial treatment. Combination drug therapy was introduced when the monotherapy failed to control the pain. Surgical intervention was the alternative choice of treatment in refractory cases. Conclusion: TN affected women more than men, and this disorder occurred most frequently in patients aged 50 years and older. The mandibular division of the trigeminal nerve was most commonly involved.     

带状疱疹后神经痛患者杏仁核的功能连接改变研究

带状疱疹后神经痛(postherpetic neuralgia,PHN)是一种常见的神经病理性疼痛,但其中枢机制尚不明了.杏仁核在疼痛反应中的作用近年来受到关注.本研究的目的在于通过功能磁共振成像,研究带状疱疹后神经痛患者杏仁核各个亚区功能连接(functional connectivity,FC)的改变,探索慢性神经病理性疼痛的中枢机制.8位带状疱疹后神经痛患者和8位健康者进行了普通核磁共振和静息态功能磁共振扫描.将杏仁核各个亚区分别进行的功能连接分析,并将功能连接和被试者的病程、视觉模拟评分(visual analog scale,VAS)进行了相关分析.与健康志愿者相比,PHN患者杏仁核的基底外侧部(laterobasal groups,LB)和皮质部(superficial groups,SF)与多个脑区的FC表现出增强,主要位于颞叶和额叶.同时SF与多个区域的FC出现减低,主要位于额叶和顶叶.颞叶和额叶部分区域与LB的FC强度、与病程长短和VAS评分表现出关联性.研究结果提示,PHN患者杏仁核功能连接的改变提示了在慢性神经病理性疼痛的产生和发展中,杏仁核以及多个涉及情绪、认知、注意的脑区发挥了重要作用.     

Fluorescence visualization of the neuropathic pain triad in trigeminal neuralgia

Trigeminal neuralgia (TN), an exemplary condition of neuropathic facial pain, seriously affects the physical and mental health of patients, becoming a major medical and social problem. So far, the mechanism of TN and its relation to neuronal activity remain unclear, largely limited by the spatial resolution of visualization methods. In the meanwhile, current therapeutic strategies targeting neurons have not achieved satisfactory outcome. Here, we investigate the neuropathic pain triad in TN by establishing an animal model of TN by chronic constriction injury of the unilateral infraorbital nerve (ION-CCI) and leveraging the single-cell resolution of confocal microscopy, including neuronal hyperexcitability, glial activation, and macrophage polarization. These results can broaden the understanding of TN pathogenesis from neurons to the neuropathic pain triad, and suggest that optical microscopy can provide new opportunities for understanding the complex pathogenesis of TN at single-cell resolution, potentially contributing to the identification of more precise therapeutic targets and the development of more effective treatment modalities.     

P2X7 receptor antagonist BBG inhibits endoplasmic reticulum stress and pyroptosis to alleviate postherpetic neuralgia

Molecular and Cellular Biochemistry - Postherpetic neuralgia (PHN) is the most common complication of acute herpes zoster. The treatment of PHN remains a challenge for clinical pain management. The...     

带状疱疹后神经痛的射频治疗

带状疱疹后神经痛(postherpetic neuralgia,PHN)是带状疱疹的严重并发症,发病机制复杂,是一种难治性、顽固性的神经病理性疼痛,常见于老年患者或免疫功能低下的患者,严重影响日常生活。带状疱疹后神经痛的治疗方法包括药物治疗、神经刺激法、射频疗法以及神经阻滞法等。其中,射频疗法作为一项临床较为常用的治疗手段,已在各种慢性疼痛的治疗上取得了有效应用。本文将综合国内外近期的相关研究,对射频的机制、射频的分类、射频治疗PHN的疗效和治疗靶点的选择进行总结。     

A method for bulbospinal trigeminal nucleotomy in the treatment of facial deafferentation pain

Many types of facial pain are difficult to treat, such as postherpetic, posttraumatic, or pain following denervation procedures used in the treatment of trigeminal neuralgia (anesthesia dolorosa), all of which involve deafferentation of the spinal trigeminal nucleus.     

The PINE study: rationale and design of a randomised comparison of epidural injection of local anaesthetics and steroids versus care-as-usual to prevent postherpetic neuralgia in the elderly [ISRCTN32866390]

BACKGROUND: Postherpetic neuralgia (PHN) is by far the most common complication of herpes zoster (HZ) and one of the most intractable pain disorders. Since PHN is seen most often in the elderly, the number of patients with this disorder is expected to increase in our ageing society. PHN may last for months to years and has a high impact on the quality of life. The results of PHN treatment are rather disappointing. Epidural injection of local anaesthetics and steroids in the acute phase of HZ is a promising therapy for the prevention of PHN. Since randomised trials on the effectiveness of this intervention are lacking, the PINE (Prevention by epidural Injection of postherpetic Neuralgia in the Elderly) study was set up. The PINE study compares the effectiveness and cost-effectiveness of a single epidural injection of local anaesthetics and steroids during the acute phase of HZ with that of care-as-usual (i.e. antivirals and analgesics) in preventing PHN in elderly patients. METHODS / DESIGN: The PINE study is an open, multicenter clinical trial in which 550 elderly (age >/= 50 yr.) patients who consult their general practitioner in the acute phase of HZ (rash < 7 days) are randomised to one of the treatment groups. The primary clinical endpoint is the presence of HZ-related pain one month after the onset of the rash. Secondary endpoints include duration and severity of pain, re-interventions aiming to treat the existing pain, side effects, quality of life, and cost-effectiveness. CONCLUSION: The PINE study is aimed to quantify the (cost-) effectiveness of a single epidural injection during the acute phase of HZ on the prevention of PHN.     

Effect of coenzyme Q10 on mitochondrial respiratory proteins in trigeminal neuralgia

Trigeminal neuralgia (TN) is the neuropathic pain. Mitochondrial dysfunction, increased oxidative stress, and inflammation demonstrated in chronic pain. Carbamazepine (CBZ) is the first-line drug for TN, however, it is still insufficient. Coenzyme Q10 (CoQ10) has been used as the additional supplement for pain therapy. Nonetheless, mitochondrial respiratory proteins, oxidative stress, and inflammation in TN, and the add-on effects of CoQ10 on those defects have never been investigated. CBZ-treated TN-patients, naïve TN-patients, and control subjects were included. CBZ-treated TN-patients were randomised into two subgroups, received either CoQ10 or placebo for 2 months. Pain levels were evaluated, and peripheral blood mononuclear cells were isolated to determine the oxidative stress, mitochondrial oxidative phosphorylation (OXPHOS), peroxisome proliferator-activated receptor gamma coactivator 1-alpha (PGC-1α), and cytokines including TNF-α, IL-1β and IL-18 mRNA expression. Pain scales, oxidative stress, and OXPHOS levels were greater in naïve TN-patients than control, whereas the cytokine profiles were unchanged. Although pain scales were lower in CBZ-treated TN-patients than in naïve TN-patients, oxidative stress, OXPHOS, and cytokine expression profiles were not different. PGC-1α levels found to be increased in CBZ-treated TN patients when compared with the naïve group. CoQ10 supplement in CBZ-treated TN patients reduced pain scale and oxidative stress and increased antioxidants levels when compared with placebo group. However, OXPHOS, PGC-1α, and cytokines were not different between groups. These findings suggest that increased oxidative stress could be potentially involved in the pathogenesis of TN. CoQ10 supplements can reduce oxidative stress, leading to more effective pain reduction in TN patients being treated with CBZ.     

Inhibition of MicroRNA-195 Alleviates Neuropathic Pain by Targeting Patched1 and Inhibiting SHH Signaling Pathway Activation

Trigeminal neuralgia (TN) is a type of chronic neuropathic pain that is caused by peripheral nerve lesions that result from various conditions, including the compression of vessels, tumors and viral infections. MicroRNAs (miRs) are increasingly recognized as potential regulators of neuropathic pain. Previous evidence has demonstrated that miR-195 is involved in neuropathic pain, but the mechanism remains unclear. To investigate the pathophysiological role of miR-195 and Shh signaling in TN, persistent facial pain was induced by infraorbital nerve chronic constriction injury (CCI-IoN), and facial pain responses were evaluated by Von Frey hairs. qPCR and Western blotting were used to determine the relative expression of miR-195 and Patched1, the major receptor of the Sonic Hedgehog (Shh) signaling pathway, in the caudal brain stem at distinct time points after CCI-IoN. Here, we found that the expression of miR-195 was increased in a rat model of CCI-IoN. In contrast, the expression of Patched1 decreased significantly. Luciferase assays confirmed the binding of miR-195 to Patched1. In addition, the overexpression of miR-195 by an intracerebroventricular (i.c.v) administration of LV-miR-195 aggravated facial pain development, and this was reversed by upregulating the expression of Patched1. These results suggest that miR-195 is involved in the development of TN by targeting Patched1 in the Shh signaling pathway, thus regulating extracellular glutamate.

     

带状疱疹后遗神经痛的动物模型及病理机制研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是带状疱疹最常见的并发症,其发生率随年龄的增加而增加,并且严重影响患者的生活质量。目前PHN的治疗多采用复合用药,但效果不佳。阻碍其治疗发展的关键是对PHN的发病机制不甚清楚,究其根本原因是缺乏与临床符合的动物模型。目的:综述带状疱疹病毒感染模型的改良和进展,使PHN的病理机制得到进一步揭示。内容:介绍与PHN相关的水痘-带状疱疹病毒潜伏感染模型、体外模型及慢性感染模型,综述与PHN发生发展有关的潜伏机制、与其他神经病理性痛相似的机制及近年来较为关注的中枢与外周损伤机制。趋向:进一步研究与人类水痘带状疱疹病毒感染更为相似的动物模型,并随其改良和进展,使发生PHN的机制得到进一步的阐释。     

Effect of duration of postherpetic neuralgia on efficacy analyses in a multicenter,randomized, controlled study of NGX-4010, an 8% capsaicin patch evaluated for the treatment of postherpetic neuralgia

Background

Postherpetic neuralgia (PHN) is a painful and difficult to treat complication of acute herpes zoster. Current treatment options provide only partial relief and are often limited by poor tolerability. We evaluated the safety and efficacy of a single 60-minute application of NGX-4010, an 8% capsaicin patch, in patients with PHN.

Methods

This multicenter, double-blind, controlled study randomized 155 patients 2:1 to receive either NGX-4010 or a 0.04% capsaicin control patch. Patients were at least 18 years old with PHN for at least 3 months, and an average Numeric Pain Rating Scale (NPRS) score of 3 to 9. The primary efficacy endpoint was the percentage change in NPRS score from baseline to weeks 2-8.

Results

The mean percent reduction in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 was greater in the NGX-4010 group (36.5%) compared with control (29.9%) although the difference was not significant (p = 0.296). PGIC analysis demonstrated that more NGX-4010 recipients considered themselves improved (much, or very much) compared with control at weeks 8 and 12, but the differences did not reach statistical significance. Post hoc analyses of patients with PHN for at least 6 months showed significantly greater reductions in "average pain for the past 24 hours" NPRS scores from baseline to weeks 2-8 in NGX-4010 patients compared to controls (37.6% versus 23.4%; p = 0.0291). PGIC analysis in this subgroup demonstrated that significantly more NGX-4010 recipients considered themselves much or very much improved compared with control at week 12 (40% versus 20%; p = 0.0403;).

Conclusions

Although treatment appeared to be safe and well tolerated, a single 60-minute application of NGX-4010 failed to show efficacy in this study which included patients with PHN for less than 6 months. Large reductions in pain observed among control patients with pain for less than 6 months may have been due to spontaneous resolution of PHN, may have confounded the results of the prespecified analyses, and should be taken into account when designing PHN studies.

Trial Registration

NCT00068081

     

Spinal astrocytic activation is involved in a virally-induced rat model of neuropathic pain

Postherpetic neuralgia (PHN), the most common complication of herpes zoster (HZ), plays a major role in decreased life quality of HZ patients. However, the neural mechanisms underlying PHN remain unclear. Here, using a PHN rat model at 2 weeks after varicella zoster virus infection, we found that spinal astrocytes were dramatically activated. The mechanical allodynia and spinal central sensitization were significantly attenuated by intrathecally injected L-α-aminoadipate (astrocytic specific inhibitor) whereas minocycline (microglial specific inhibitor) had no effect, which indicated that spinal astrocyte but not microglia contributed to the chronic pain in PHN rat. Further study was taken to investigate the molecular mechanism of astrocyte-incudced allodynia in PHN rat at post-infection 2 weeks. Results showed that nitric oxide (NO) produced by inducible nitric oxide synthase mediated the development of spinal astrocytic activation, and activated astrocytes dramatically increased interleukin-1β expression which induced N-methyl-D-aspartic acid receptor (NMDAR) phosphorylation in spinal dorsal horn neurons to strengthen pain transmission. Taken together, these results suggest that spinal activated astrocytes may be one of the most important factors in the pathophysiology of PHN and "NO-Astrocyte-Cytokine-NMDAR-Neuron" pathway may be the detailed neural mechanisms underlying PHN. Thus, inhibiting spinal astrocytic activation may represent a novel therapeutic strategy for clinical management of PHN.     

家族性三叉神经痛

三叉神经痛是一种临床常见疾病,典型的三叉神经痛主要表现为阵发性、闪电样的疼痛发作,疼痛剧烈,常无法忍受,呈电灼、针刺、撕裂样,每次发作持续时间数秒至数分钟不等。疼痛多发生于单侧,常有扳机点表现,其多表现为散发,而家族性三叉神经痛报道罕见,至今世界范围内报道仅50余个家系,其临床表现及发病特点与散发性三叉神经痛存在明显差别,尽管散发三叉神经痛患者的病因为责任血管压迫三叉神经REZ区已被普遍接受,但关于家族性三叉神经痛的病因是否为血管压迫存在争议,其遗传模式也没有达成一致的意见,文章复习了相关文献,并通过对这些文献进行分析综合,结合我们治疗三叉神经痛的经验,对其病因、发病机制、诊断和治疗原则、遗传模式等作了系统综述。     

Sensorimotor and Pain Modulation Brain Abnormalities in Trigeminal Neuralgia: A Paroxysmal,Sensory-Triggered Neuropathic Pain

Objective

Idiopathic trigeminal neuralgia (TN) is characterized by paroxysms of severe facial pain but without the major sensory loss that commonly accompanies neuropathic pain. Since neurovascular compression of the trigeminal nerve root entry zone does not fully explain the pathogenesis of TN, we determined whether there were brain gray matter abnormalities in a cohort of idiopathic TN patients. We used structural MRI to test the hypothesis that TN is associated with altered gray matter (GM) in brain areas involved in the sensory and affective aspects of pain, pain modulation, and motor function. We further determined the contribution of long-term TN on GM plasticity.

Methods

Cortical thickness and subcortical GM volume were measured from high-resolution 3T T1-weighted MRI scans in 24 patients with right-sided TN and 24 healthy control participants.

Results

TN patients had increased GM volume in the sensory thalamus, amygdala, periaqueductal gray, and basal ganglia (putamen, caudate, nucleus accumbens) compared to healthy controls. The patients also had greater cortical thickness in the contralateral primary somatosensory cortex and frontal pole compared to controls. In contrast, patients had thinner cortex in the pregenual anterior cingulate cortex, the insula and the orbitofrontal cortex. No relationship was observed between GM abnormalities and TN pain duration.

Conclusions

TN is associated with GM abnormalities in areas involved in pain perception, pain modulation and motor function. These findings may reflect increased nociceptive input to the brain, an impaired descending modulation system that does not adequately inhibit pain, and increased motor output to control facial movements to limit pain attacks.     

Changes in expression of nociceptin/orphanin FQ and its receptor in spinal dorsal horn during electroacupuncture treatment for peripheral inflammatory pain in rats

The neuropeptide nociceptin/orphanin FQ (N/OFQ), the endogenous agonist of the N/OFQ peptide receptor (NOP receptor), has been demonstrated to be involved in many physiological and pathological functions including pain modulation. It was reported that electroacupuncture (EA) had a potent analgesic effect on inflammatory pain by activating various endogenous transmitters such as the opioid peptides. In the present study, we investigated the effect of EA on peripheral inflammatory pain and the expression of N/OFQ and the NOP receptor in the spinal dorsal horn of rats, using a behavioral test, RT-PCR, immunohistochemistry and Western blot analysis techniques. The results showed: (1) EA had an accumulative analgesic effect on chronic inflammatory pain; (2) in the superficial layers of the spinal dorsal horn, the level of mRNA of the precursor protein for N/OFQ (preproN/OFQ, ppN/OFQ) was increased and the N/OFQ immunoreactivity was decreased after peripheral inflammation, and could be significantly increased by EA treatment; (3) both mRNA and protein levels of the NOP receptor in the spinal dorsal horn were significantly increased after chronic inflammatory pain and could be further enhanced by EA treatment. The present data demonstrated that EA could activate the endogenous N/OFQ-NOP receptor system, and this might underlie the effectiveness of EA in the treatment of inflammatory pain.     

Sensory symptom profiles and co-morbidities in painful radiculopathy

Painful radiculopathies (RAD) and classical neuropathic pain syndromes (painful diabetic polyneuropathy, postherpetic neuralgia) show differences how the patients express their sensory perceptions. Furthermore, several clinical trials with neuropathic pain medications failed in painful radiculopathy. Epidemiological and clinical data of 2094 patients with painful radiculopathy were collected within a cross sectional survey (painDETECT) to describe demographic data and co-morbidities and to detect characteristic sensory abnormalities in patients with RAD and compare them with other neuropathic pain syndromes. Common co-morbidities in neuropathic pain (depression, sleep disturbance, anxiety) do not differ considerably between the three conditions. Compared to other neuropathic pain syndromes touch-evoked allodynia and thermal hyperalgesia are relatively uncommon in RAD. One distinct sensory symptom pattern (sensory profile), i.e., severe painful attacks and pressure induced pain in combination with mild spontaneous pain, mild mechanical allodynia and thermal hyperalgesia, was found to be characteristic for RAD. Despite similarities in sensory symptoms there are two important differences between RAD and other neuropathic pain disorders: (1) The paucity of mechanical allodynia and thermal hyperalgesia might be explained by the fact that the site of the nerve lesion in RAD is often located proximal to the dorsal root ganglion. (2) The distinct sensory profile found in RAD might be explained by compression-induced ectopic discharges from a dorsal root and not necessarily by nerve damage. These differences in pathogenesis might explain why medications effective in DPN and PHN failed to demonstrate efficacy in RAD.     

Percutaneous Radio-Frequency Rhizotomy in the Treatment of Trigeminal Neuralgia

A percutaneous technique of selective partial trigeminal root coagulation was evaluated in the treatment of 38 patients suffering from trigeminal neuralgia, 1 patient with pain secondary to oral carcinoma and 1 patient with atypical facial pain. The pain of trigeminal neuralgia was relieved in 94.7 percent of patients. Pain was relieved in the patient with oral carcinoma, but not in the patient with atypical facial pain. There was no mortality and no permanent morbidity outside of the trigeminal nerve lesion. The procedure requires only a brief hospital stay without the time, expense and hazards of open cranial surgical procedures.     

带状疱疹后遗神经痛患者脑基础活动改变的功能核磁共振研究

带状疱疹后遗神经痛(postherpetic neuralgia,PHN)是临床上一种慢性顽固性神经病理性疼痛,然而,对于其潜在的中枢机制还知之甚少.为了进一步探讨带状疱疹后遗神经痛患者的相关脑区活动,利用功能核磁共振成像低频振幅振荡(ALFF)技术观察带状疱疹后遗神经痛患者的基础脑区活动.8名带状疱疹后遗神经痛患者与8名性别、年龄相匹配的健康者行静息态功能磁共振(f MRI)成像扫描,用SPM8中的多重回归分析,在控制被试年龄、性别、教育年限的影响下,将每个体素的ALFF值同每个被试的病程、视觉模拟评分(visual analog scale,VAS)进行相关分析.与健康志愿者相比,PHN组与VAS评分相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA11/46/47)、右侧顶叶(BA40)、右侧舌回(BA17/18/19);与VAS评分相关的ALFF值降低的脑区有:右侧颞中回(BA21)、左侧舌回(BA17/18)、右侧小脑前叶、左侧后扣带回(BA30/19)和右侧中央前回(BA3/4/6);PHN组与病程相关的ALFF值增高的脑区有:右侧小脑后叶、前额叶背外侧区域(BA9/10/11/47)、左侧颞上回(BA38)、右侧顶叶和右侧舌回(BA17/18/19);与病程相关ALFF值降低的脑区有:左侧海马旁回(BA28)、右侧小脑前叶、左侧扣带回(BA24)、右侧颞上回(BA13)、左侧中央前回和右侧顶下小叶(BA39/40).研究结果提示,涉及疼痛的情绪、警觉行为、注意的脑区在带状疱疹后遗痛慢性疼痛的产生和维持中发挥重要作用.