Reassessment of the diagnostic value of selective lumbosacral radiculography

In nerve root infiltration (NRI) consisting of neural blockage and radiculography, response to the nerve root block has usually been thought to be diagnostically significant. However radiculography has not been statistically evaluated. The purpose of this paper is to assess the value of selective radiculography of patients with group 1 response (typical pain reproduced by needle placement and then relieved by nerve root block) according to Dooley's criteria. We studied selective radiculography in a consecutive series of 88 patients with lumbo-sacral radicular pain who showed group 1 response in NRI. The accuracy of the preoperative nerve root block and radiculography in 88 nerve roots (L5,S1) were correlated with the intraoperative findings. Selective radiculograms were classified into three groups; normal (absence of block), partial block, and complete block. The tilting angle of all nerve roots was measured. We found the symptomatic root at the same level of the nerve root block in all 88 patients. Selective radiculograms showed five normal roots, 15 roots with incomplete block and 63 roots with complete block. Fifteen radiculograms had abnormal tilting angles. The accuracy of radiculography was 84% in the canal zone and 100% in the intra and extraforaminal zones. If the L5 nerve root angle was more than 60(o), an intra or extraforaminal lesion was strongly suggested (P<0.01). Radiculography of patients with group 1 response is useful for detecting compressed sites in the symptomatic nerve root, particularly for detecting lesions in the intra and extraforaminal zones.     

枕下乙状窦后入路选择性舌咽神经迷走神经切断术治疗舌咽神经痛

目的探讨枕下乙状窦后入路选择性舌咽神经、迷走神经部分根丝切断术治疗舌咽神经痛的有效性及安全性。 方法选择自2010年4月至2015年6月收治于陆军总医院附属八一脑科医院的原发性舌咽神经痛患者34例,其中12例行微血管减压（MVD）+舌咽神经根切断术（PR）,22例行PR+迷走神经根1~2组根丝切断术（VR）,观察远期治愈率、近期并发症及远期并发症。两组患者远期疗效、近期总并发症及远期总并发症的发生采用百分率（%）表示,率之间的比较使用卡方检验。 结果MVD+PR组术后10例立即无疼痛,2例仍有疼痛,2例术后有复发,远期治愈率66.7%;PR+VR组术后21例立即无疼痛,1例仍有疼痛,无复发,远期治愈率95.5%;PR+VR组患者远期治愈率高于MVD+PR组患者,且差异有统计学意义（χ²=5.130,P<0.05）。MVD+PR组共3例有近期并发症,近期总并发症发生率25.0%,PR+VR组共10例有近期并发症,近期总并发症发生率45.5%,两组间近期总并发症发生率差异无统计学意义（χ²=1.376,P>0.05）;MVD+PR组共2例遗留远期并发症,远期总并发症发生率16.7%,PR+VR组共5例遗留远期并发症,远期总并发症发生率22.7%,两组间远期总并发症发生率差异无统计学意义（χ²=0.174,P>0.05）。 结论选择性PR+VR是安全的,其疗效优于MVD+PR,应积极选择PR+VR治疗GPN。     

Reg-Ⅲβ和C-fosmRNA在尼莫地平抗大鼠背根反射介导的神经病理痛中的作用

目的研究C-fos及Reg-Ⅲβ在大鼠背根反射介导的神经病理痛中的表达变化;并探讨尼莫地平治疗对其的影响。方法建立SD大鼠选择性坐骨神经损伤(SNI)模型,采用Von Frey纤维丝测量不同时间点手术侧后肢的机械痛阈。采用实时荧光定量聚合酶链式反应(RT-qPCR)检测坐骨神经损伤后不同时间内Reg-Ⅲβ及C-fos的mRNA表达,以及不同剂量尼莫地平治疗对这些分子表达的影响。结果与-1 d相比,1、3、5、7、14 d大鼠其SNI术后各时间段脊髓背角组织中的Reg-Ⅲβ及C-fos mRNA表达均普遍上调。腹腔注射尼莫地平对Reg-ⅢβmRNA的表达上调产生明显的时间和剂量依赖性的抑制作用。模型组大鼠的机械痛阈在SNI术后1 d即明显低于基础痛阈,术后5 d降至最低,随后缓慢恢复。尼莫地平治疗后大鼠机械痛阈仍呈下降趋势,但其幅度较模型组显著减小,且术后转归时间显著提前。这些治疗效果随药物浓度提升而明显加大。结论选择性坐骨神经损伤可引起大鼠脊髓背角组织中C-fos及Reg-ⅢβmRNA表达发生时序性变化,尼莫地平能显著减轻神经病理性痛并缩短疼痛转归时间,其机制可能与逆转背根神经节介导的脊髓背角中C-fos及Reg-Ⅲβ的病理性表达有关。     

Case Report: Successful Epiradicular Peripheral Nerve Stimulation of the C2 Dorsal Root Ganglion for Postherpetic Neuralgia

Background: Postherpetic neuralgia (PHN) is the most common complication following an acute varicella zoster virus infection. PHN often results in a chronic severe pain condition refractory to conservative pain management treatments. Peripheral nerve stimulation over the affected spinal nerve root may be an effective treatment option for patients with intractable PHN. Objective: To describe a successful case of peripheral nerve stimulation of the second cervical dorsal root ganglion for the treatment of intractable PHN. Case Report: An 80‐year‐old man with a 15‐month history of severe PHN was referred to our clinic for pain management. His pain was localized to the left side in the distribution of the C2 dermatome. The patient's pain was unresponsive to comprehensive conventional treatments for PHN including physical therapy, membrane stabilizing medications, opioids, anti‐inflammatories, cervical epidural steroid injections, cervical facet joint injections, and dorsal root ganglion blockade with pulsed radiofrequency. After failing to respond to conservative and interventional therapies, a peripheral nerve stimulator trial was conducted for a period of seven days. The lead was placed within the epidural space over the atlanto–axial joint under fluoroscopy to stimulate the left C2 nerve root. This trial resulted in a significant decrease of the patient's pain, and discontinuation of all pain medications. Conclusion: We describe a case of successful electrode placement at the C2 spinal level for the treatment of refractory PHN.     

Operative findings in cases of trigeminal neuralgia without vascular compression: proposal of a different mechanism.

Trigeminal neuralgia is known to be caused by vascular compression at the trigeminal root entry zone (REZ) and microvascular decompression provides good outcome in most of cases. However, in some cases, no vascular compression was observed at the REZ. Over the last 2(1/2) years, the first author operated on 53 cases of trigeminal neuralgia with microvascular decompression and encountered nine cases where no offending vessels were noted at or near the REZ. They were divided into two groups: five cases involving an initial operation and four cases involving a second operation. In the former, arachnoid thickening, angulation or torsion of the root axis were common findings. Dissection of thick arachnoid around the root along the whole length reversed the root to be straight and flaccid. Complete pain relief was noted in four of five cases. In one case of atypical pain, constant facial pain remained. In the latter four cases, where the first operations were done more than 4 years before, thick granulation was noted around REZ without new offending vessels in two cases. In the remaining two cases, where no offending vessels were noted in the first operation, thick adhesion of a distal portion of the root with dura on the pyramidal bone was noted. Meticulous dissection of t he whole length of the root was done and complete pain relief was obtained. Delayed but complete pain relief in these nine cases was noted. Based on operative findings, arachnoid thickening or granulomatous adhesion between the root and surrounding structures can cause an abnormal course of the trigeminal nerve root, which causes root angulation and/or torsion. They can also cause pulsatile movement of the trigeminal nerve root. This tethering effect can promote abnormal root stretching force, especially at REZ, which might promote hyperexitability of the nerve.This speculative mechanism suggests that it is important to make the root free along the entire length, especially at its distal portion in cases with no offending vessels.     

Unusual clinical variants and signs in Guillain-Barré syndrome

Limited regional forms of the Guillain-Barré syndrome (GBS) and unusual focal signs or symptoms that resemble other illnesses are described: pharyngeal-cervical-brachial weakness with ptosis, sparing power, and reflexes in the legs; paraparesis with normal power and reflexes in the arms; early severe ptosis without other signs of oculomotor weakness; and acute severe midline back pain at the onset. The first two variants did not progress to typical generalized GBS, delaying the proper diagnosis. Regional and functional variants suggest that the pathologic, and perhaps immunologic abnormalities of GBS can be localized and selective.     

p38 activation in uninjured primary afferent neurons and in spinal microglia contributes to the development of neuropathic pain induced by selective motor fiber injury

Compelling evidence shows that the adjacent uninjured primary afferents play an important role in the development of neuropathic pain after nerve injury. The underlying mechanisms, however, are largely unknown. In the present study, the selective motor fiber injury was performed by L5 ventral root transection (L5 VRT), and p38 activation in dorsal root ganglia (DRG) and L5 spinal dorsal horn was examined. The results showed that phospho-p38 immunoreactivity (p-p38-IR) was increased in both L4 and L5 DRGs, starting on day 1 and persisting for nearly 3 weeks (P<0.05) following L5 VRT and that the activated p38 was confined in neurons, especially in IB4 positive C-type neurons. L5 VRT also induced p38 activation in L5 spinal dorsal horn, occurred at the first day after the lesion and lasted for 2 weeks (P<0.05). The activated p38 is restricted entirely in spinal microglia. In contrast, selective injury of sensory neurons by L5 dorsal root transection (L5 DRT) failed to induce behavioral signs of neuropathic pain and activated p38 only in L5 DRG but not in L4 DRG and L5 spinal dorsal horn. Intraperitoneal injection of thalidomide, an inhibitor of TNF-alpha synthesis, prevented p38 activation in DRG and spinal cord. Intrathecal injection of p38 inhibitor SB203580, starting before L5 VRT, inhibited the abnormal pain behaviors. Post-treatment with SB203580 performed at the 1st day or at the 8th day after surgery also reduced established neuropathic pain. These data suggest that p38 activation in uninjured DRGs neurons and in spinal microglia is necessary for the initiation and maintenance of neuropathic pain induced by L5 VRT.     

Taking one’s time in feeling other-race pain: an event-related potential investigation on the time-course of cross-racial empathy

Using the event-related potential (ERP) approach, we tracked the time-course of white participants’ empathic reactions to white (own-race) and black (other-race) faces displayed in a painful condition (i.e. with a needle penetrating the skin) and in a nonpainful condition (i.e. with Q-tip touching the skin). In a 280–340 ms time-window, neural responses to the pain of own-race individuals under needle penetration conditions were amplified relative to neural responses to the pain of other-race individuals displayed under analogous conditions. This ERP reaction to pain, whose source was localized in the inferior frontal gyrus, correlated with the empathic concern ratings of the Interpersonal Reactivity Index questionnaire. In a 400–750 ms time-window, the difference between neural reactions to the pain of own-race individuals, localized in the middle frontal gyrus and other-race individuals, localized in the temporoparietal junction was reduced to nil. These findings support a functional, neural and temporal distinction between two sequential processing stages underlying empathy, namely, a race-biased stage of pain sharing/mirroring followed by a race-unbiased stage of cognitive evaluation of pain.     

脑干三叉神经诱发电位对三叉神经根部分切断术的临床应用研究

目的 评价脑干三叉神经诱发电位对三叉神经痛病人三叉神经根切断术的临床应用价值.方法 作者研究了36例经术前MRTA及术中探查除外神经血管接触的三叉神经痛病人,在三叉神经感觉根大部切断术过程中,通过术前、中、后记录BTEP以监测三叉神经传导功能;测定BTEP潜伏期及波幅参量的变化指导手术的进程.结果 36例病人患侧BTEP潜伏期延长、波幅降低,提示三叉神经痛患者三叉神经传导功能损害,术中待BTEP呈一直线后,不再继续切断神经根,术后疼痛均缓解,未遗三叉运动功能障碍.结论 脑干三叉神经诱发电位可以指导选择性三叉神经根切断术并防止三叉神经眼支损害的发生.     

Nerve injury proximal or distal to the DRG induces similar spinal glial activation and selective cytokine expression but differential behavioral responses to pharmacologic treatment

The specific mechanisms by which nervous system injury becomes a chronic pain state remain undetermined. Historically, it has been believed that injuries proximal or distal to the dorsal root ganglion (DRG) produce distinct pathologies that manifest in different severity of symptoms. This study investigated the role of injury site relative to the DRG in (1) eliciting behavioral responses, (2) inducing spinal neuroimmune activation, and (3) responding to pharmacologic interventions. Rats received either an L5 spinal nerve transection distal to the DRG or an L5 nerve root injury proximal to the DRG. Comparative studies assessed behavioral nociceptive responses, spinal cytokine mRNA and protein expression, and glial activation after injury. In separate studies, intrathecal pharmacologic interventions by using selective cytokine antagonists (interleukin-1 [IL-1] receptor antagonist and soluble tumor necrosis factor [TNF] receptor) and a global immunosuppressant (leflunomide) were performed to determine their relative effectiveness in these injury paradigms. Behavioral responses assessed by mechanical allodynia and thermal hyperalgesia were almost identical in the two models of persistent pain, suggesting that behavioral testing may not be a sensitive measure of injury. Spinal IL-1beta, IL-6, IL-10, and TNF mRNA and IL-6 protein were significantly elevated in both injuries. The overall magnitude of expression and temporal patterns were similar in both models of injury. The degree of microglial and astrocytic activation in the L5 spinal cord was also similar for both injuries. In contrast, the pharmacologic treatments were more effective in alleviating mechanical allodynia for peripheral nerve injury than nerve root injury, suggesting that nerve root injury elicits a more robust, centrally mediated response than peripheral nerve injury. Overall, these data implicate alternate nociceptive mechanisms in these anatomically different injuries that are not distinguished by behavioral testing or the neuroimmune markers used in this study.     

三叉神经痛伽玛刀放射外科治疗（附43例分析）

目的：评价伽玛刀（γ－刀）放射外科治疗三叉神经痛（TN）43例治疗结果。方法：采用1．5TD磁共振成像（MRI）、GammaPlan治疗计划系统,Leksellγ－刀治疗34例非肿瘤性TN,治疗靶点在三叉神经感觉根桥脑进入区,单个4mm准直器,最大剂量72－90Gy,50％等计量线限定靶点;9例颅底肿瘤的症状性三叉神经痛边缘剂量12－15Gy。结果：随访3－28个月,平均随访期14．8个月,疼痛100％缓解占69．8％,疼痛缓解＞80％占18．6％,疼痛缓解＞50％占46％,总有效率93％,非肿瘤性TN总有效率90l％。缓解疼痛＜50％3例（7．0％）。3例疼痛缓解后分别在5、9和17个月复发。无效和复发病人经再次治疗后疼痛有效缓解。全组病人无任何并发症,无死亡。结论：γ－刀是治疗三叉神经痛安全和有效的治疗方法。     

Quantification of neural tissue injury in a rat radiculopathy model: comparison of local deformation, behavioral outcomes, and spinal cytokine mRNA for two surgeons

Clinical and experimental work indicate that a variety of factors contribute to radicular pain mechanisms, including mechanical injury. While it has been qualitatively suggested that the magnitude of nerve root mechanical injury affects the nature of the pain response, no study has quantified the local in vivo injury biomechanics in these models. Therefore, it was the purpose of this study to develop and implement an in vivo method to quantify compressive nerve root injury strain severity and characterize its effect on the resulting responses in an existing lumbar radiculopathy rat model. Male Holtzman rats were divided into a sham group with only nerve root exposure or a ligation group with the nerve root tightly ligated using silk suture. Using image analysis, nerve root radial strains were calculated at the time of injury for two surgeons. Mechanical allodynia was continuously assessed throughout the study and spinal cord cytokine mRNA levels were assayed on postoperative day 7. The degree of intersurgeon variability for imposing a ligation injury in this model was also assessed. Mean compressive injury strains in the nerve root were 32.8+/-14.2% and were not different for the two experimenters. Animals undergoing more severe ligation strains exhibited significantly heightened allodynia following injury and greater upregulation of the inflammatory cytokines IL-1alpha/beta, IL-6, and IL-10. Results indicate a direct correlation of local nerve root injury severity with the ensuing physiologic responses associated with nociception.     

Treatment of atypical trigeminal neuralgia with microvascular decompression

AIM: To explore the methods for achieving pain relief in patients with atypical trigeminal neuralgia (TN) using microvascular decompression (MVD). STUDY DESIGN AND SETTINGS: Retrospective study of 26 patients treated during the years 2000 to 2004. MATERIALS AND METHODS: Twenty-six patients in whom vascular compression of the trigeminal nerve was identified by high definition magnetic resonance tomographic angiography (MRTA) were treated with MVD for atypical TN in our department. Clinical presentations, surgical findings and clinical outcomes were analyzed retrospectively. RESULTS: In this study, single trigeminal division was involved in only 2 patients (8%) and two or three divisions in the other 24 patients (92%). Of prime importance is the fact that in 46.2% of the patients, several conflicting vessels were found in association. Location of the conflicts around the circumference of the trigeminal root was supero-medial to the root in 53.5%, supero-lateral in 30.8% and inferior in 15.7%. MVD for atypical TN resulted in complete pain relief in 50% of the patients with complete decompression, partial pain relief in 30.8% and poor pain relief or pain recurrence in 19.2% of the patients without complete decompression postoperatively. CONCLUSIONS: Complete decompression of the entire trigeminal root plays an important role in achieving pain relief in patients with atypical TN with MVD.     

Endothelin-1 activates ET(A) receptors to increase intracellular calcium in model sensory neurons.

Endothelin-1 (ET-1) induces endothelin-A (ETA) receptor-mediated pain and selective excitation of nociceptors. Here we studied ET-1-induced changes in intracellular calcium (Ca2+in) in Fura-2 loaded mouse neuroblastoma-rat dorsal root ganglion hybrid cells (ND7/104). ET-1 (1-400 nM) induced concentration-dependent, transient increases in Ca2+in, probably of intracellular source. Responses to repeated application declined with increasing ET-1 concentration, implying receptor desensitization. Treatment of cells with the selective ETA receptor antagonist, BQ-123, produced a dose-dependent inhibition of the response that was 20% of ET-1 alone (IC50 = 20 nM, KI = 7 nM). No inhibition of the calcium response was observed with the selective ETB antagonist, BQ-788 (10-1000 nM). These results demonstrate that ET-1 induces dose- and ETA receptor-dependent release of Ca2+in in nociceptor-like neurons, and permit further examination of the pathways that underlie ET-1-induced pain signaling.     

Targeting the NMDA receptor subunit NR2B for the treatment of neuropathic pain

Neuropathic pain is generally defined as a chronic pain state resulting from peripheral or central nerve injury, or both. An effective treatment for neuropathic pain is still lacking. The NMDA receptor, one type of the ionotropic glutamate receptors, is known to be important for triggering long-lasting changes in synapses. NMDA receptor-dependent synaptic plasticity plays roles not only in physiological functions such as learning and memory, but also in unwanted pathological conditions such as chronic pain. This review addresses recent progress on NMDA receptors in neuropathic pain, with particular emphasis on the NR2B-subunit-containing receptors. The expression and function of NMDA receptors in synaptic plasticity in the pain transmission pathway from dorsal root ganglia to the anterior cingulate cortex is reviewed, and preclinical and clinical investigations of selective NMDA receptor in neuropathic pain are discussed. The NMDA receptors, in particular NR2B-containing NMDA receptors, serve as promising targets for treatment of neuropathic pain.     

Inflammation-induced hyperexcitability of nociceptive gastrointestinal DRG neurones: the role of voltage-gated ion channels

Gastrointestinal (GI) inflammation modulates the intrinsic properties of nociceptive dorsal root ganglia neurones, which innervate the GI tract and these changes are important in the genesis of abdominal pain and visceral hyperalgesia neurones exhibit hyperexcitability characterized by a decreased threshold for activation and increased firing rate, and changes in voltages-gated Na(+) and K(+) channels play a major role in this plasticity. This review highlights emerging evidence that specific subsets of channels and signalling pathways are involved and their potential to provide novel selective therapeutics targets for the treatment of abdominal pain.     

A model of chronic pain in the rat: high-resolution neuroanatomical approach identifies alterations in multiple opioid systems in the periaqueductal grey

Inoculation of the tail base of rats with Mycobacterium butyricum led to an arthritic swelling and inflammation of the limbs which displayed a hyperalgesia to noxious pressure: these effects peaked at 3 weeks postinoculation. In vitro autoradiography of coronal sections of rat brain was used for a parallel determination of binding to mu-, delta- and kappa-opioid binding sites. In only two regions, the dorsomedial and dorsolateral parts of the periaqueductal grey (PAG), was a significant change seen: this comprised an increase in binding to kappa-sites, whereas mu- and delta-sites therein were unaffected. This region was analysed for opioid peptides derived from each of the three opioid peptide families known. While no change was seen in levels of immunoreactive (ir)-dynorphin1-17 A (DYN) and ir-Met-enkephalin, a decrease was detected in those of ir-beta-endorphin (beta-EP): this change was restricted to the PAG. These data demonstrate a highly localized and selective influence of chronic arthritic pain upon multiple opioid systems in the PAG of the rat, a structure playing a key role in the control of pain and in the expression of the antinociceptive actions of opioids. The data suggest a possible significance of PAG pools of beta-EP and kappa-receptors in the response to and modulation of chronic pain.     

Somatosensory evoked potentials in cerebral palsy after partial dorsal root rhizotomy

Somatosensory evoked potentials (SEPs) were studied in 20 children with cerebral palsy and severe lower extremity spasticity before and after selective partial dorsal root rhizotomy of the lumbosacral cord. The potentials from stimulating nerves in the lower extremity were abnormal in two thirds of the children before the operation, whereas the potentials were generally normal from upper extremity nerves. Dorsal root rhizotomies caused an attenuation of nerve root entry volleys recorded over the lumbar cord but did not change SEPs recorded over the cortex. The exception to this was that the incidence of abnormal sural nerve SEPs decreased postoperatively. Lumbar cord functions measured by H-reflexes or by tendon jerks were depressed following the operation. These results indicate a significant degree of abnormality of somatosensory transmission from the lower extremity in a group of cerebral palsied children with severe spasticity. Moreover, selective sectioning of approximately 50% of the dorsal root fibers in the lumbosacral cord had little influence on cortical evoked potentials.