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Background: Transforaminal epidural injections with steroids (TESI) are increasingly being used in patients sciatica. The STAR (steroids against radiculopathy)-trial aimed to evaluate the (cost-) effectiveness of TESI in patients with acute sciatica (< 8 weeks). This article contains the economic evaluation of the STAR-trial., Methods: Participants were randomized to one of three study arms: Usual Care (UC), that is oral pain medication with or without physiotherapy, n = 45); intervention group 1: UC and transforaminal epidural steroid injection (TESI) 1 ml of 0.5% Levobupivacaine and 1 ml of 40 mg/ml Methylprednisolone and intervention group 2: UC and transforaminal epidural injection (TEI) with 1 ml of 0,5% Levobupivacaine and 1 ml of 0.9% NaCl (n = 50). The primary effect measure was health-related quality of life. Secondary outcomes were pain, functioning, and recovery. Costs were measured from a societal perspective, meaning that all costs were included, irrespective of who paid or benefited. Missing data were imputed using multiple imputation, and bootstrapping was used to estimate statistical uncertainty., Results: None of the between-group differences in effects were statistically significant for any of the outcomes (QALY, back pain, leg pain, functioning, and global perceived effect) at the 26-weeks follow-up. The adjusted mean difference in total societal costs was €1718 (95% confidence interval [CI]: - 3020 to 6052) for comparison 1 (intervention group 1 versus usual care), €1640 (95%CI: - 3354 to 6106) for comparison 2 (intervention group 1 versus intervention group 2), and €770 (95%CI: - 3758 to 5702) for comparison 3 (intervention group 2 versus usual care). Except for the intervention costs, none of the aggregate and disaggregate cost differences were statistically significant. The maximum probability of all interventions being cost-effective compared to the control was low (< 0.7) for all effect measures., Conclusion: These results suggest that adding TESI (or TEI) to usual care is not cost-effective compared to usual care in patients with acute sciatica (< 8 weeks) from a societal perspective in a Dutch healthcare setting., Trial Registration: Dutch National trial register: NTR4457 (March, 6th, 2014)., (© 2024. The Author(s).)

The purpose of this study is to compare the accuracy and effectiveness of ultrasound-guided and fluoroscopy-guided lumbar selective nerve root block (SNRB), and to explore the feasibility of ultrasound-guided methods. This retrospective study included patients with lumbar radicular pain who underwent ultrasound-guided and fluoroscopy-guided selective nerve root block at Honghui Hospital Affiliated to Xi'an Jiaotong University from August 2020 to August 2022. Patients were divided into U-SNRB group and F-SNRB group according to ultrasound-guided or fluoroscopy-guided selective nerve root block. There were 43 patients in U-SNRB group and 20 patients in F-SNRB group. The pain visual analogue scale (VAS) scores, Japanese Orthopaedic Association (JOA) scores, related indexes and complications were recorded and compared between the two groups before, 30 min, 1 month and 6 months after block. To evaluate the feasibility, accuracy and effectiveness of ultrasound-guided selective nerve root block. There were no complications in the process of selective nerve root block in both groups. The operating time and the times of closing needle angle adjustment in U-SNRB group were better than those in F-SNRB group, and the difference was statistically significant (P < 0.05). The VAS score and JOA score of patients in the two groups were significantly improved 30 min after block, 1 month and 6 months after block, and the difference was statistically significant (P < 0.05). There was no significant difference between the two groups (P > 0.05). The accuracy of ultrasound-guided selective nerve root block and the degree of pain relief of patients were similar to those of fluoroscopy guidance, but the operation time and needle angle adjustment times were significantly less than that of fluoroscopy, and could effectively reduce radiation exposure. Therefore, it can be used as a better way to guide for choice., (© 2024. The Author(s).)

Isolated deep infiltrating endometriosis (DIE) of sacral nerve roots or major pelvic nerves, including the sciatic nerve, is considered to be extremely rare. Due to the overlap with sciatica symptoms, the diagnosis of sciatica DIE is difficult yet crucial, as it results in permanent neural damage if left untreated. We report a case of a 45-year-old woman who experienced a three-year-long and recently exacerbating pain in her right leg, accompanied by a tingling sensation and weakness in her right leg and foot, with difficulty walking. In between regular menstrual bleedings, when her aforementioned symptoms worsened, she had been experiencing mild 10-day extra-cyclical bleeding. Her neurologist's, orthopedist's, and gynecological examinations were unremarkable. Magnetic resonance imaging (MRI) showed an infiltrative lesion on the right sciatic nerve that was immunohistochemically confirmed to be endometriosis. The patient was treated with gonadotropin-releasing hormone analogues (GnRHa), which led to a significantly diminished size of the lesion on the control MRI, and endometriosis remission was obtained. For persistent mild, but cyclical, pain and muscle weakness, continuous progestagnes were administered, with advice for physical therapy provided for her neuro-muscle rehabilitation and a scheduled check-up in 6 months.

Purpose: The aim of the present paper was to assess neuropathic pain and its predictors among patients with sciatica. In addition, we sought to investigate the predictors of functional disability in sciatica patients with neuropathic pain., Methods: A cross-sectional study was carried out on a sample of 100 sciatica patients aged 18 years and older with a radiating pain from the lower back down to the leg below the knee. Information about socio-demographic characteristics, duration of symptoms, being treated or not, type of treatment, side of sciatica, presence of back pain, leg pain occurrence, leg pain intensity, functional disability and pain catastrophizing were collected., Results: Of the total patients, 57% had neuropathic pain. Multivariable analysis showed that leg pain intensity was higher in the neuropathic pain group as compared to the non-neuropathic pain group. Also, patients with left sciatica were less likely to have neuropathic pain than patients with right sciatica. Patients with neuropathic pain having high levels of pain catastrophizing and being on bed rest for at least one week were at a higher risk of developing functional disability as compared to their counterparts., Conclusion: Low levels of pain catastrophizing and less bed rest should be considered in interventions aimed at improving the functional ability for sciatica patients with neuropathic pain.

Abstract: Pain radiating from the spine into the leg is commonly referred to as "sciatica," "Sciatica" may include various conditions such as radicular pain or painful radiculopathy. It may be associated with significant consequences for the person living with the condition, imposing a reduced quality of life and substantial direct and indirect costs. The main challenges associated with a diagnosis of "sciatica" include those related to the inconsistent use of terminology for the diagnostic labels and the identification of neuropathic pain. These challenges hinder collective clinical and scientific understanding regarding these conditions. In this position paper, we describe the outcome of a working group commissioned by the Neuropathic Pain Special Interest Group (NeuPSIG) of the International Association for the Study of Pain (IASP) which was tasked with the following objectives: (1) to revise the use of terminology for classifying spine-related leg pain and (2) to propose a way forward on the identification of neuropathic pain in the context of spine-related leg pain. The panel recommended discouraging the term "sciatica" for use in clinical practice and research without further specification of what it entails. The term "spine-related leg pain" is proposed as an umbrella term to include the case definitions of somatic referred pain and radicular pain with and without radiculopathy. The panel proposed an adaptation of the neuropathic pain grading system in the context of spine-related leg pain to facilitate the identification of neuropathic pain and initiation of specific management in this patient population., (Copyright © 2023 The Author(s). Published by Wolters Kluwer Health, Inc. on behalf of the International Association for the Study of Pain.)

Background/aim: Sleep deprivation may lead to individual and social insufficiency associated with many physiological and psychological pathologies. This study is reported to investigate sleep quality and the relationship between treatment modalities of lumbar disc herniation, which is the most common cause of chronic lower back pain and sciatica., Materials and Methods: This present study was conducted on 249 cases with chronic lower back pain and sciatica caused by a single- level lumbar disc herniation diagnosed after lumbar MRI (Magnetic Resonance Imaging) between June 2017 and September 2019. Cases were divided into three groups according to the treatment modalities: early surgical treatment (n:80), extended conservative treatment (n:142), and medical treatment only (n:27). VAS (Visual Analog Scale) and PSQI (Pittsburgh Sleep Quality Index) data before the treatment and 6 months after the treatment were statistically analyzed., Results: It was determined that post-treatment VAS and PSQI scores were significantly reduced in all cases, regardless of the differences in treatment modalities (p < 0.05). In the early surgical treatment group, VAS score was improved by 69% and PSQI score was improved by 63.8%. These values were 28.5% and 38.6% in the extended conservative treatment. However, VAS score was increased by 27% in the patients who received only medical treatment. Statistical analysis of the treatment modalities showed that early surgical treatment was superior to the other treatment modalities (p < 0.05)., Conclusions: It was determined that early surgical treatment of lumbar disc herniation was superior to other treatment methods in terms of maintaining the sleep quality impairments associated with deterioration in sleep quality., (Copyright © 2022 Elsevier Ltd. All rights reserved.)

Competing Interests: The authors declare no conflict of interest.

Background: The aim of our observational study is to compare the therapeutic efficacy of combined treatment of oxygen-ozone therapy and oral treatment with alpha-lipoic acid (ALA) + palmitoylethanolamide (PEA) and myrrh in patients with peripheral neuropathic pain (sciatica) on radicular disc conflict from disc herniation and the results obtained with oxygen-ozone treatment alone., Methods: We enrolled 318 patients with the neuroradiological diagnosis of disc herniation performed with computed tomography (CT) or magnetic resonance imaging (MRI) and symptoms characterized by low back pain complicated by sciatica, which we divided into two groups. Group A was composed of 165 patients who were treated only with oxygen-ozone therapy with CT-guided intraforaminal technique, while the remaining 153 (Group B) have undergone combined oral treatment with ALA + PEA and myrrh. Follow-up visits for the evaluation of the clinical outcome of the treatment were conducted after 60 ± 8 days using a modified version of McNab's method., Results: At the clinical check-up, 126/165 patients included in Group A had a complete remission of pain (76.4%), while in Group B, 119/153 (77.8%) had a complete remission of pain., Conclusion: The results highlight how the treatment associated with ozone therapy and oral administration of alpha-lipoic acid + palmitoylethanolamide and myrrh is preferred over the simple treatment with only ozone in such patients in the phase of greatest acuity of the disease, where the pain appears to be better controlled.

BACKGROUND The intervertebral disc extrusion resorption has been described in the literature by various authors. It occurs in up to 75% of patients with symptomatic extruded lumbar discs. The Atlasprofilax method favors osteo-musculo-articular rehabilitation processes, mainly impacting on 2 levels: the first is the bone anatomy of the atlanto-occipital joint, and the second is the fasciae located in the cervical region. CASE REPORT A 42-year-old male patient diagnosed by MRI with dehydration of L2-L3 to L5-S1 intervertebral discs, disc bulging at L2-L3 and L3-L4, and disc extrusion at L4-L5, received a one-time neuromuscular treatment, called the Atlasprofilax method, to the suboccipital region. In a repeat MRI 6 months later, the disc extrusion at L4-L5 was totally resorbed and improvement in the L3-L4 and L4-L5 disc bulges was seen. The patient's symptoms prior to the Atlasprofilax treatment included bilateral trapezius pain, right brachialgia, constant chronic low back pain, right sciatica, gait claudication, and paresthesia and dysesthesias in the lower limbs with associated pain and numbness in the calves. These symptoms were ameliorated after the treatment. The sciatica disappeared 1 week after the treatment and did not recur. In a follow-up 5 years later, the remaining symptoms had improved even further. CONCLUSIONS We propose that alterations of the cervical musculature and deep fascia could predispose to the development of lumbar disc abnormalities. We therefore also propose that improvements in this patient, both in symptoms and in imaging findings, are due to a reduction of the asymmetric distribution of forces and elastic loading as a result of the Atlasprofilax treatment.

Objective: To assess whether percutaneous transforaminal endoscopic discectomy (PTED) is non-inferior to conventional open microdiscectomy in reduction of leg pain caused by lumbar disc herniation., Design: Multicentre randomised controlled trial with non-inferiority design., Setting: Four hospitals in the Netherlands., Participants: 613 patients aged 18-70 years with at least six weeks of radiating leg pain caused by lumbar disc herniation. The trial included a predetermined set of 125 patients receiving PTED who were the learning curve cases performed by surgeons who did not do PTED before the trial., Interventions: PTED (n=179) compared with open microdiscectomy (n=309)., Main Outcome Measures: The primary outcome was self-reported leg pain measured by a 0-100 visual analogue scale at 12 months, assuming a non-inferiority margin of 5.0. Secondary outcomes included complications, reoperations, self-reported functional status as measured with the Oswestry Disability Index, visual analogue scale for back pain, health related quality of life, and self-perceived recovery. Outcomes were measured until one year after surgery and were longitudinally analysed according to the intention-to-treat principle. Patients belonging to the PTED learning curve were omitted from the primary analyses., Results: At 12 months, patients who were randomised to PTED had a statistically significantly lower visual analogue scale score for leg pain (median 7.0, interquartile range 1.0-30.0) compared with patients randomised to open microdiscectomy (16.0, 2.0-53.5) (between group difference of 7.1, 95% confidence interval 2.8 to 11.3). Blood loss was less, length of hospital admission was shorter, and timing of postoperative mobilisation was earlier in the PTED group than in the open microdiscectomy group. Secondary patient reported outcomes such as the Oswestry Disability Index, visual analogue scale for back pain, health related quality of life, and self-perceived recovery, were similarly in favour of PTED. Within one year, nine (5%) in the PTED group compared with 14 (6%) in the open microdiscectomy group had repeated surgery. Per protocol analysis and sensitivity analyses including the patients of the learning curve resulted in similar outcomes to the primary analysis., Conclusions: PTED was non-inferior to open microdiscectomy in reduction of leg pain. PTED resulted in more favourable results for self-reported leg pain, back pain, functional status, quality of life, and recovery. These differences, however, were small and may not reach clinical relevance. PTED can be considered as an effective alternative to open microdiscectomy in treating sciatica., Trial Registration: NCT02602093ClinicalTrials.gov NCT02602093., Competing Interests: Competing interests: All authors have completed the ICMJE uniform disclosure form at www.icmje.org/disclosure-of-interest/ and declare: financial support from ZonMw, the Netherlands Organisation for Health Research and Development; no financial relationships with any organisations that might have an interest in the submitted work in the previous three years; no other relationships or activities that could appear to have influenced the submitted work., (© Author(s) (or their employer(s)) 2019. Re-use permitted under CC BY-NC. No commercial re-use. See rights and permissions. Published by BMJ.)

Aim: This SR aims to assess the effectiveness of pregabalin and gabapentin on pain and disability caused by acute sciatica and the adverse events associated with their clinical use., Design: Systematic review., Databases: Electronic databases of Cochrane Central Register of Controlled Trials, MEDLINE, EMBASE, and Clinical Trials.gov were searched from their inception until March 1st of 2021., Selection Criteria: Randomized trials (RCT) with adults>18 years old with acute sciatica for a minimum of 1 week and a maximum of 1 year (at least moderate pain)., Data Treatment: The outcomes were pain, disability and adverse events. Data was summarized using odds ratio and mean difference. GRADE was used to calculate the level of evidence., Results: Eight RCT involving 747 participants were included. The effect of pregabalin was assessed in 3 RCT and in one three-arm trial (pregabalin vs limaprost vs a combination of limaprost and pregabalin). Two trials assessed the effect of gabapentin compared with placebo and one compared with tramadol. One study assessed the effect of gabapentin vs pregabalin in a crossover head-to-head trial. A statistically significant improvement on leg pain at 2 weeks and leg pain with movement at 3 and 4 months was found in a RCT comparing gabapentin with placebo. There were no statistically differences on the remaining time periods assessed for leg pain, low back pain and functional disability., Conclusions: This SR provides clear evidence for lack of effectiveness of pregabalin and gabapentin for sciatica pain management. In view of this, its routine clinical use cannot be supported., (Copyright © 2021 The Author(s). Publicado por Elsevier España, S.L.U. All rights reserved.)

The role of obesity in the development of dorsopathies is still unclear. In this study, we assessed the associations between body mass index (BMI) and several dorsopathies including intervertebral disc degeneration (IVDD), low back pain (LBP), and sciatica by using the Mendelian randomization method. We also assessed the effect of several obesity-related traits on the same outcomes. Single-nucleotide polymorphisms associated with the exposures are extracted from summary-level datasets of previously published genome-wide association studies. Summary-level results of IVDD, LBP, and sciatica were from FinnGen. In our univariable Mendelian randomization analysis, BMI is significantly associated with increased risks of all dorsopathies including sciatica (OR = 1.33, 95% CI, 1.21-1.47, p = 5.19 × 10 -9 ), LBP (OR = 1.28, 95% CI, 1.18-1.39, p = 6.60 × 10 -9 ), and IVDD (OR = 1.23, 95% CI, 1.14-1.32, p = 2.48 × 10 -8 ). Waist circumference, hip circumference, whole-body fat mass, fat-free mass, and fat percentage, but not waist-hip ratio, were causally associated with increased risks of IVDD and sciatica. Higher hip circumference, whole-body fat mass, fat-free mass, and fat percentage increased the risk of LBP. However, only whole-body fat-free mass remained to have a significant association with the risk of IVDD after adjusting for BMI with an odds ratio of 1.57 (95% CI, 1.32-1.86, p = 2.47 × 10 -7 ). Proportions of BMI's effect on IVDD, sciatica, and LBP mediated by leisure sedentary behavior were 41.4% (95% CI, 21.8%, 64.8%), 33.8% (95% CI, 17.5%, 53.4%), and 49.7% (95% CI, 29.4%, 73.5%), respectively. This study provides evidence that high BMI has causal associations with risks of various dorsopathies. Weight control is a good measure to prevent the development of dorsopathies, especially in the obese population., Competing Interests: The authors declare that the research was conducted in the absence of any commercial or financial relationships that could be construed as a potential conflict of interest., (Copyright © 2021 Zhou, Mi, Peng, Han and Liu.)

Background: Few studies have examined primary care management for acute sciatica, including referral to physical therapy., Objective: To evaluate whether early referral to physical therapy reduced disability more than usual care (UC) alone for patients with acute sciatica., Design: Randomized controlled clinical trial. (ClinicalTrials.gov: NCT02391350)., Setting: 2 health care systems in Salt Lake City, Utah., Patients: 220 adults aged 18 to 60 years with sciatica of less than 90 days' duration who were making an initial primary care consultation., Intervention: All participants received imaging and medication at the discretion of the primary care provider before enrollment. A total of 110 participants randomly assigned to UC were provided 1 session of education, and 110 participants randomly assigned to early physical therapy (EPT) were provided 1 education session and then referred for 4 weeks of physical therapy, including exercise and manual therapy., Measurements: The primary outcome was the Oswestry Disability Index (OSW) score after 6 months. Secondary outcomes were pain intensity, patient-reported treatment success, health care use, and missed workdays., Results: Participants in the EPT group had greater improvement from baseline to 6 months for the primary outcome (relative difference, -5.4 points [95% CI, -9.4 to -1.3 points]; P = 0.009). The OSW and several secondary outcomes favored EPT after 4 weeks. After 1 year, between-group differences favored EPT for the OSW (relative difference, -4.8 points [CI, -8.9 to -0.7 points]) and back pain intensity (relative difference, -1.0 points [CI, -1.6 to -0.4 points]). The EPT group was more likely to self-report treatment success after 1 year (45.2%) than the UC group (27.6%) (relative risk, 1.6 [CI, 1.1 to 2.4]). There were no significant differences in health care use or missed workdays., Limitation: The patients and providers were unblinded, and specific physical therapy interventions responsible for effects could not be determined., Conclusion: Referral from primary care to physical therapy for recent-onset sciatica improved disability and other outcomes compared with UC., Primary Funding Source: Agency for Healthcare Research and Quality.

Abdominal aneurysm is a common pathology that affects mainly men and for which there are many risk factors. This pathology predominantly stays asymptomatic until rupture and symptoms depend on location. We report the case of a 71-year-old patient. She is presenting herself to the emergency room for a nagging pain, typical of a left cruralgia as she is both febrile and shivering. The abdominal scanner is showing a ruptured infra renal aortic aneurysm. The patient is transferred to universities for an uncomplicated stent. Despite a cruralgia that seemed quite banal, both clinical and anamnestic arguments suggested an abdominal aortic rupture., Competing Interests: Les auteurs n’ont déclaré aucun conflit d’intérêts en relation avec cet article.

Lumbosacral disc herniation (LDH) represents the most common cause of sciatica. Currently, there is limited evidence about minimally invasive interventional therapies for the treatment of this condition. This paper presents the protocol for a multicenter, prospective, randomized, controlled, phase III trial evaluating if PRF in addition to TFESI leads to better outcomes in patients with sciatica due to LDH, compared to TFESI alone, during the first year after treatment (Pulsed Radiofrequency in Addition to TFESI for Sciatica [PRATS]). Eligible patients are between 18 and 75 years of age, suffer from sciatica of less than 12-week duration with pain intensity >4 on the Visual Analogue Scale (VAS) and have unilateral LDH compatible with symptoms at MRI. The Medical Ethics Committee of participating hospitals approved the study protocol. Patients will be randomized to receive either combined treatment (PRF and TFESI) or TFESI alone. The primary outcome will be the assessment of pain intensity with VAS at different timepoints from week-1 to 52 after treatment; secondary outcomes will include Roland Disability Questionnaire for sciatica and Oswestry Disability Index, evaluated at 4, 12 and 52 weeks. The follow-up will last 52 weeks for each patient. Statistical analysis will be performed on a per-protocol basis.

Sciatica as a clinical diagnosis is nonspecific. A diagnosis of sciatica is typically used as a synonym for lumbosacral radiculopathy. However, the differential for combined low back and leg pain is broad, and the etiology can be one several different conditions. The lifetime prevalence of sciatica ranges from 12.2% to 43%, and nonsuccessful outcomes of treatment are prevalent. Nurse practitioners and other primary care clinicians often have minimal training in differential diagnosis of the complex causes of lower back and leg pain, and many lack adequate time per patient encounter to work up these conditions. Differentiating causes of low back and leg pain proves challenging, and inadequate or incomplete diagnoses result in suboptimal outcomes. Chiropractic care availability may lessen demands of primary care with respect to spinal complaints, while simultaneously improving patient outcomes. The authors describe three patients referred from primary care with a clinical diagnosis of sciatica despite differing underlying pathologies. More precise clinical terminology should be used when diagnosing patients with combined low back and leg pain. Nurse practitioners and other clinicians' triage, treat, and determine appropriate referrals for low back and leg pain. Multidisciplinary care including chiropractic may add value in settings where patients with lower back and leg pain are treated.

Objectives: The aim of this study was to identify independent predictors of conservative treatment failure in patients presenting due to lumbar disc herniation-associated low back pain and sciatica., Patients and Methods: This is a single institution, case-control study including 240 patients that were selected for microsurgical or conservative treatment due to lumbar disc herniation in a 2,5-year period. Bivariate and multivariate analyses were performed in order to identify independent predictors among demographic, clinical and radiographic factors., Results: Statistically significant differences were observed between conservatively and surgically managed groups in bivariate analysis. Logistic regression models further revealed that leg paresthesia (p =  0,003; OR = 5,136) and percentage of spinal canal stenosis ratio (p < 0,001; OR = 1,055) had the strongest, independent correlation with conservative treatment failure in our cohort. Back-to-leg ratio did not reach statistical significance although it proved a strong correlation in bivariate analysis (p < 0,001, Cramér's V = 0,53)., Conclusion: Increasing % canal compromise ratio (cut-off value 23%) and co-occurrence of leg paresthesia were the most important risk factors for surgery in our series of patients., Competing Interests: Declaration of Competing Interest None., (Copyright © 2020 Elsevier B.V. All rights reserved.)

Background: Lumbosciatica is a common condition that affects patients' quality of life., Objective: To determine the efficacy of Vojta Therapy and transcutaneous electrical nerve stimulation (TENS) in the treatment of lumbosciatica., Methods: A "pre-post" quasi-experimental pilot study was carried out on 12 patients between 31 and 74 years of age who had been diagnosed with lumbosciatica and referred to the Physiotherapy Unit of the Quintanar de la Orden Health Center. Subjects were prescribed either TENS or Vojta, assigned alternately (6:6). All patients received one session of 30 min per day for 15 days. Tests to evaluate pain, disability, functionality, and radiculopathy were performed., Results: The differences between pre-post measures and improvement after both treatments were analyzed with nonparametric tests. Significant improvements were noted after both treatments in indices for pain, disability, and flexibility, with the exception of disability after TENS, according to the Roland-Morris test (p = 0.066). Improvements in radiculopathy (Làsegue sign) were only observed with Vojta (p = 0.031). An overall decrease in scores obtained after Vojta was observed with respect to those obtained after TENS (difference V-T): pain according to the Visual Analog Scale (V-T = 2.84; p = 0.033) or Oswestry back pain (V-T = 2.67; p = 0.030) and leg pain tests (V-T = 3.25; p = 0.063); disability according to Oswestry (V-T = 28.33; p = 0.005) and Roland-Morris (V-T = 5.67; p = 0.044); flexibility according to Schöber (average gain V-T = 0.43; p = 0.292) and the fingertips to floor distance test (V-T = 7.5; p = 0.016)., Conclusions: Vojta Therapy led to significantly greater improvements in pain, disability, flexibility, and radiculopathy than TENS. Future studies will require larger samples to confirm these findings., (Copyright © 2019 Elsevier Ltd. All rights reserved.)

Case History: Dairy cows recumbent following calving on farms in South Gippsland, Australia were examined during two 3-month seasonal calving periods in 2011 and 2012 as part of a larger study of 218 recumbent cows. A cohort of 104 cows diagnosed with calving paralysis following dystocia was derived from the larger group, which were examined with 3 days of becoming recumbent. A thorough medical and musculoskeletal clinical examination was performed on each cow including flexor-withdrawal and patellar reflex tests, and postural assessment in the lifted position, unless the facilities were not available. Cows were diagnosed with one or more neurological syndromes: sciatic, tibial paresis, obturator or femoral, based on clinical findings consistent with damage to these peripheral nerves or their nerve roots. Clinical Findings: Evidence of sciatic syndrome was found in 100/104 (96.2%) cows and 146/172 (84.9%) affected hind limbs either as the sole neuropathy or in combination with tibial paresis, obturator or femoral syndromes. Pelvic damage was also present in 3/104 (2.8%) cows. Obturator syndrome was diagnosed in 30/104 (29%) cows and 45/172 (26.2%) affected hind limbs but not apparently as the sole reason for the recumbency. Femoral syndrome occurred in 16/104 (15.4%) cows and 21/172 (12.2%) affected hind limbs and was the only syndrome recorded in one cow. Clinical Relevance: Sciatic syndrome was the most common neurological syndrome observed in cows with calving paralysis. The other major nerves arising from the lumbo-sacral plexus were also affected and the various syndromes associated with damage to these nerves or their ventral nerve roots occurred in many combinations. Calving paralysis should be thought of as a paresis or paralysis resulting from damage to the ventral nerve roots of the lumbo-sacral plexus as any of the nerves originating from this plexus can be damaged during dystocia either individually or in combination with other nerves from the plexus.

Chronic pain is frequently accompanied by the manifestation of emotional disturbances and cognitive deficits. While a causality relation between pain and emotional/cognitive disturbances is generally assumed, several observations suggest a temporal dissociation and independent mechanisms. We therefore studied Sprague-Dawley rats that presented a natural resistance to pain manifestation in a neuropathy model (spared nerve injury [SNI]) and compared their performance in a battery of behavioral paradigms-anxiety, depression and fear memory-with animals that presented a pain phenotype. Afterward, we performed an extensive volumetric analysis across prefrontal, orbitofrontal and insular cortical areas. The majority of SNI animals manifested mechanical allodynia (low threshold [LT]), but 13% were similar to Sham controls (high threshold [HT]). Readouts of spontaneous hypersensivity (paw flinches) were also significantly reduced in HT and correlated with allodynia. To increase the specificity of our findings, we segregated the SNI animals in those with left (SNI-L) and right (SNI-R) lesions and the lack of association between pain and behavior still remains. Left-lesioned animals, independent of the LT or HT phenotype, presented increased anxiety-like behaviors and decreased well-being. In contrast, we found that the insular cortex (agranular division) was significantly smaller in HT than in LT. To conclude, pain and emotional disturbances observed following nerve injury are to some extent segregated phenomena. Also, HT and LT SNI presented differences in insular volumes, an area vastly implicated in pain perception, suggesting a supraspinal involvement in the manifestation of these phenotypes., (© 2018 John Wiley & Sons Ltd and International Behavioural and Neural Genetics Society.)

Background: There is increasing interest in the role of pro-inflammatory cytokines in the pathogenesis of sciatica and whether these could be potential targets for treatment. We sought to investigate serum biomarker levels in patients with low back-related leg pain, including sciatica., Methods: Primary care consulters aged > 18 with low back-related leg pain were recruited to a cohort study (ATLAS). Participants underwent a standardised clinical assessment, lumbar spine MRI and a subsample (n = 119) had samples taken for biomarker analysis. Participants were classified having: a) clinically confirmed sciatica or referred leg pain, and then subdivided into those with (or without) MRI confirmed nerve root compression due to disc prolapse. Seventeen key cytokines, chemokines and matrix metalloproteinases (MMPs) implicated in sciatica pathogenesis including TNFα and IL-6, were assayed in duplicate using commercial multiplex detection kits and measured using a Luminex suspension array system. Median biomarker levels were compared between the groups using a Mann Whitney U test. Multivariate logistic regression analysis was used to investigate the association between clinical measures and biomarker levels adjusted for possible confounders such as age, sex, and symptom duration., Results: No difference was found in the serum level of any of the 17 biomarkers tested in patients with (n = 93) or without (n = 26) clinically confirmed sciatica, nor between those with (n = 44) or without (n = 49) sciatica and MRI confirmed nerve root compression., Conclusion: In this cohort, no significant differences in serum levels of TNFα, IL-6 or any other biomarkers were seen between patients with sciatica and those with back pain with referred leg pain. These results suggest that in patients with low back-related leg pain, serum markers associated with inflammation do not discriminate between patients with or without clinically confirmed sciatica or between those with or without evidence of nerve root compression on MRI.

The aim of this study was to assess the effects of the general strenuousness of work and various physical exposures on the risk of hospitalization for sciatica. The study population consisted of Finns aged 30 to 59 who had participated in a national health examination survey in 1978-80 (N = 3891). The participants were followed up until the end of 2011 and information on work-related determinants was acquired by a questionnaire. After adjustment for confounders, sedentary work involving handling fairly heavy objects/physically light work (HR 1.57; 95% CI 1.05-2.34), lifting or carrying heavy objects (2.10; 1.35-3.26) and exposure to whole-body vibration (1.61; 0.95-2.72) predicted sciatica, whereas heavier workloads appeared to reduce its risk (0.48; 0.26-0.89). There was an interaction between body mass index and exposure to whole-body vibration for the risk of sciatica. Overweight (1.94; 0.96-3.93) and obese (3.50; 1.44-8.46) participants exposed to whole-body vibration were at an increased risk of sciatica. Individuals of normal weight who were exposed to vibration, and overweight and obese individuals who were not exposed to vibration were not at an increased risk. The risk of hospitalization for sciatica seems to be highest among obese individuals exposed to whole-body vibration and among those lifting or carrying heavy objects.

Neuropathic pain genesis is related to gene alterations in the dorsal root ganglion (DRG) after peripheral nerve injury. Transcription factors control gene expression. In this study, we investigated whether octamer transcription factor 1 (OCT1), a transcription factor, contributed to neuropathic pain caused by chronic constriction injury (CCI) of the sciatic nerve. Chronic constriction injury produced a time-dependent increase in the level of OCT1 protein in the ipsilateral L4/5 DRG, but not in the spinal cord. Blocking this increase through microinjection of OCT1 siRNA into the ipsilateral L4/5 DRG attenuated the initiation and maintenance of CCI-induced mechanical allodynia, heat hyperalgesia, and cold allodynia and improved morphine analgesia after CCI, without affecting basal responses to acute mechanical, heat, and cold stimuli as well as locomotor functions. Mimicking this increase through microinjection of recombinant adeno-associated virus 5 harboring full-length OCT1 into the unilateral L4/5 DRG led to marked mechanical allodynia, heat hyperalgesia, and cold allodynia in naive rats. Mechanistically, OCT1 participated in CCI-induced increases in Dnmt3a mRNA and its protein and DNMT3a-mediated decreases in Oprm1 and Kcna2 mRNAs and their proteins in the injured DRG. These findings indicate that OCT1 may participate in neuropathic pain at least in part by transcriptionally activating Dnmt3a and subsequently epigenetic silencing of Oprm1 and Kcan2 in the DRG. OCT1 may serve as a potential target for therapeutic treatments against neuropathic pain.

Background: Despite being widely prescribed, relatively few controlled trials have been conducted on the class of neurotrophic/antinociceptive nutraceuticals. While performing a search in the literature, we came across an old registration study on micronized palmitoylethanolamide in patients with low back pain - sciatica by Guida and colleagues., Methods: We contacted the authors of the article and obtained all the original material, which allowed us to reanalyze the study. We assessed its clinical relevance by calculating the numbers needed to treat for pain (visual analog scale) and function (Roland-Morris Questionnaire). After excluding patients for whom the information available was insufficient, we assigned each patient to one of the five categories of increasing probability of neuropathic pain: pure lumbago, lumbago with projecting pain to surrounding regions (e.g. gluteus or groin), lumbago with projecting pain to the thigh or leg, pure sciatica and radiculopathy, and investigated any correlations (Spearman) between the improvement in pain and function with these five classes., Results: Compared with placebo, palmitoylethanolamide 600 mg/die yielded a number needed to treat of 1.7 (95% confidence interval: 1.4-2) for pain, and 1.5 (95% confidence interval: 1.4-1.7) for function. The correlation between the five categories was highly significant for pain relief (P <0.0001), though not significant for reduced dysfunction., Conclusion: Palmitoylethanolamide was extremely effective on pain and function in a large cohort of patients with low back pain - sciatica. Although, the multiple mechanisms of action of palmitoylethanolamide are ideal for mixed pain conditions such as low back pain - sciatica, the correlation between pain relief and the likelihood of neuropathic pain suggests that this drug exerts a predominant action on the neuropathic pain component., (Copyright© Bentham Science Publishers; For any queries, please email at epub@benthamscience.net.)

Piriformis syndrome (PS) is a rare etiology of extra-spinal sciatica in which pathologies associated with or around the piriformis muscle (PM) irritate the adjacent sciatic nerve (SN), however, there is scarcity in the literature regarding its exact etiologies, thus, we performed a retrospective study to elucidate the epidemiology of PS and assess various causes of the syndrome. Our study included patients assessed at our institution who presented with sciatica of non-spinal origin between May 2014 and December 2015. Radiology reports of all patients who received pelvic MRI were examined for positive findings involving PM and SN. Of the 143 patients recognized with sciatica and negative lumbar pathology, 24 patients (17%) exhibited positive PM and SN findings. Average patient age was 50.0 ± 15.1 years (range: 21-75), and 17 were female. Seven patients (5%; 4M/3F) presented with tumor, seven patients (5%) had chronic inflammatory changes, one patient had SN adhesions to obturator muscle, three patients (2%, 3F) had aberrant anatomy, and the remaining patients had positive MRI findings, such as nerve atrophy or PM hypertrophy without identifiable cause. Seven patients received steroid injections in the peri-sciatic fossa, and four displayed poor response. Our findings suggested possible trends in extra-spinal sciatica. Affected males appeared more likely to present with tumor, while affected females were more likely to present younger, but with aberrant anatomy. Steroid injections appeared to be suboptimal in most cases. Pelvic MRI is helpful in patients with sciatica and negative spine imaging to rule out neoplastic involvement., (Copyright © 2018 Elsevier Ltd. All rights reserved.)

Sciatica is a common form of low back pain (LBP) that has been identified as distinct both in terms of the persistence and severity of symptoms. Little research has explored individual experiences of sciatica, and none focuses on individuals with the most severe, long-lasting symptoms who may experience the most profound impact. This paper addresses this gap through proposing a theoretical framework for understanding such experiences, that of biographical suspension as a form of liminality of Self. Twenty semi-structured interviews were conducted with individuals with severe sciatic symptoms between January 2016‒March 2017, as part of the UK-based SCOPiC (SCiatica Outcomes in Primary Care) randomised controlled trial. Data were analysed thematically using the constant comparison method. The concept of 'biographical suspension', originally developed in LBP, emerged as one whereby individuals put life on-hold in the expectation of an eventual return to their former, pain-free selves. Deeper analysis extended this concept to a form of liminality, whereby individuals are caught between pre- and post-sickness selves, unable to fully identify with either. This liminality is underpinned by ongoing beliefs about sciatica as a temporary and fixable 'injury' rather than long-term 'illness', even among those with long-lasting symptoms. This led to a disjuncture between individuals' ongoing pain beliefs and experiences, resulting in longer-term psychological impacts. Biographical suspension is further conceptualised as an experiential stage giving rise to four distinct short-term trajectories: i) symptom resolution leading individuals to occupy a clearly post-liminal state; ii) remaining in suspended liminality; iii) ongoing symptoms leading to a post-liminal state of resignation; ix) a state of being both between sickness and wellness, and straddling hope and fear; thus exemplifying differing states of liminality experienced over time. Findings have implications for the support provided in clinical settings to individuals who may struggle to self-manage due to sustained liminality of Self., (Copyright © 2018. Published by Elsevier Ltd.)

Chronic sciatica is a major cause of disability worldwide, but accurate diagnosis of the causative pathology remains challenging. In this report, the feasibility of an 18 F-FDG PET/MRI approach for improved diagnosis of chronic sciatica is presented. Methods: 18 F-FDG PET/MRI was performed on 9 chronic sciatica patients and 5 healthy volunteers (healthy controls). Region-of-interest analysis using SUV max was performed, and 18 F-FDG uptake in lesions was compared with that in the corresponding areas in healthy controls. Results: Significantly increased 18 F-FDG uptake was observed in detected lesions in all patients and was correlated with pain symptoms. 18 F-FDG-avid lesions not only were found in impinged spinal nerves but also were associated with nonspinal causes of pain, such as facet joint degeneration, pars defect, or presumed scar neuroma. Conclusion: The feasibility of 18 F-FDG PET/MRI for diagnosing pain generators in chronic sciatica was demonstrated, revealing various possible etiologies., (© 2018 by the Society of Nuclear Medicine and Molecular Imaging.)

Background: Sciatica-related Foot Drop is a peripheral nervous condition that produces a loss of power in the ankle dorsiflexion muscles. Functional electrical stimulation is a modality of electrical stimulation that produces muscle contraction in a functional movement of the limb. This technique was utilized with positive effects in central nervous afflictions but it is not known whether or not it has any influence in motor recovery following peripheral nervous system problems. This study aims to clarify the effects of functional electrical stimulation on foot drop caused by peripheral nerve compression resulting from lumbar disc herniation., Methods: Fifty patients were enrolled in our study; of whom 25 were treated with EMG triggered electrical stimulation (EMG-FES) and 25 with heel-floor sensor triggered electrical stimulation (SWITCH-FES) during normal gait cycle. Patients received functional electrical stimulation (with a pulse of 60 Hz and phase duration of 200 ms) once a day, for 30 minutes during 5 consecutive days, over a period of 4 weeks. Electrical diagnostic tests (nerve conduction velocity/NCV and the amplitude of compound muscle action potential/CMAP), dynamometry and Osvestry Disability Index scores were measured at baseline and after treatment., Results: We found that axonal loss was lower in the EMG-FES group than in the SWITCH-FES group (p< 0.004). The motor functional recovery was higher in terms of muscle force and overall functional status for the EMG-FES group compared to the SWITCH-FES group. This was underlined by Dynamometry test with a p value of < 0.0001 and ODI score with a statistical significant p value of < 0.0001., Conclusions: The overall results showed that there was a significant increase in all the parameters studied for both types of FES applications. However we found that the EMG triggered electrical stimulation technique had a higher influence on the quality of the muscle action control. For patients who cannot yet produce minimal muscle active contraction we recommend switch triggered stimulation first and then, immediately after the recovery of the motor control, to change to EMG triggered functional electrical stimulation.

Background: Clinical studies show that prenatal alcohol exposure (PAE) results in effects that persist into adulthood. Experimental animal models of moderate PAE demonstrate that young adults with PAE display potentiated sensitivity to light touch, clinically termed allodynia, following sciatic nerve chronic constriction injury (CCI) that coincides with heightened spinal glial, spinal macrophage, and peripheral immune responses. However, basal touch sensitivity and corresponding glial and leukocyte activation are unaltered. Therefore, the current study explored whether the enduring pathological consequences of moderate PAE on sensory processing are unmasked only following secondary neural insult., Methods: In middle-aged (1 year) Long Evans rats that underwent either prenatal saccharin exposure (control) or moderate PAE, we modified the well-characterized model of sciatic neuropathy, CCI, to study the effects of PAE on neuro-immune responses in adult offspring. Standard CCI manipulation required 4 chromic gut sutures, while a mild version applied a single suture loosely ligated around one sciatic nerve. Spinal glial immunoreactivity was examined using immunohistochemistry. The characterization and functional responses of leukocyte populations were studied using flow cytometry and cell stimulation assays followed by quantification of the proinflammatory cytokines interleukin-1beta (IL-1β) and tumor necrosis factor-alpha (TNF-α). Data were statistically analyzed by ANOVA and unpaired t tests., Results: The current report demonstrates that mild CCI generates robust allodynia only in PAE rats, while the pathological effects of PAE following the application of a standard CCI are revealed by enhanced allodynia and elevated spinal glial activation. Additionally, mild CCI increases spinal astrocyte activation but not microglia, suggesting astrocytes play a larger role in PAE-induced susceptibility to aberrant sensory processing. Leukocyte populations from PAE are altered under basal conditions (i.e., prior to secondary insult), as the distribution of leukocyte populations in lymphoid organs and other regions are different from those of controls. Lastly, following in vitro leukocyte stimulation, only PAE augments the immune response to antigen stimulation as assessed by heightened production of TNF-α and IL-1β., Conclusions: These studies demonstrate PAE may prime spinal astrocytes and peripheral leukocytes that contribute to enduring susceptibility to adult-onset neuropathic pain that is not apparent until a secondary insult later in life.

Background: Up to 15% of all spontaneous subarachnoid hemorrhages (SAH) have a non-aneurysmal SAH (NASAH). The evaluation of SAH patients with negative digital subtraction angiography (DSA) is sometimes a diagnostic challenge. Our goal in this study was to reassess the yield of standard MR-imaging of the complete spinal axis to rule out spinal bleeding sources in patients with NASAH., Methods: We retrospectively analyzed the spinal MRI findings in 190 patients with spontaneous NASAH, containing perimesencephalic (PM) and non-perimesencephalic (NPM) SAH, diagnosed by computer tomography (CT) and/or lumbar puncture (LP), and negative 2nd DSA., Results: 190 NASAH patients were included in the study, divided into PM-SAH (n = 87; 46%) and NPM-SAH (n = 103; 54%). Overall, 23 (22%) patients had a CT negative SAH, diagnosed by positive LP. MR-imaging of the spinal axis detected two patients with lumbar ependymoma (n = 2; 1,05%). Both patients complained of radicular sciatic pain. The detection rate raised up to 25%, if only patients with radicular sciatic pain received an MRI., Conclusion: Routine radiological investigation of the complete spinal axis in NASAH patients is expensive and can not be recommended for standard procedure. However, patients with clinical signs of low-back/sciatic pain should be worked up for a spinal pathology.

Neuropathic pain is a major unmet medical need, with only 30% to 35% of patients responding to the current standard of care. The discovery and development of novel therapeutics to address this unmet need have been hampered by poor target engagement, the selectivity of novel molecules, and limited access to the relevant compartments. Biological therapeutics, either monoclonal antibodies (mAbs) or peptides, offer a solution to the challenge of specificity as the intrinsic selectivity of these kinds of molecules is significantly higher than traditional medicinal chemistry-derived approaches. The interleukin-1 receptor system within the spinal cord has been implicated in the amplification of pain signals, and its central antagonism provides relief of neuropathic pain. Targeting the IL-1 system in the spinal cord with biological drugs, however, raises the even greater challenge of delivery to the central compartment. Targeting the transferrin receptor with monoclonal antibodies has proved successful in traversing the endothelial cell-derived blood-brain barrier and delivering proteins to the central nervous system. In this study, we describe a novel construct exemplifying an engineered solution to overcome these challenges. We have generated a novel anti-transferrin receptor-interleukin-1 receptor antagonist fusion that transports to the central nervous system and delivers efficacy in a model of nerve ligation-induced hypersensitivity. Approaches such as these provide promise for novel and selective analgesics that target the central compartment.

Study Design: Prospective cohort study., Objective: To identify potential prognostic factors for persistent leg-pain at 12 months among patients hospitalized with acute severe sciatica., Summary of Background Data: The long-term outcome for patients admitted to hospital with sciatica is generally unfavorable. Results concerning prognostic factors for persistent sciatica are limited and conflicting., Methods: A total of 210 patients acutely admitted to hospital for either surgical or nonsurgical treatment of sciatica were consecutively recruited and received a thorough clinical and radiographic examination in addition to responding to a comprehensive questionnaire. Follow-up assessments were done at 6 weeks, 6 months, and 12 months. Potential prognostic factors were measured at baseline and at 6 weeks. The impact of these factors on leg-pain was analyzed by multiple linear regression modeling., Results: A total of 151 patients completed the entire study, 93 receiving nonrandomized surgical treatment. The final multivariate models showed that the following factors were significantly associated with leg-pain at 12 months: high psychosocial risk according to the Örebro Musculosceletal Pain Questionnaire (unstandardized beta coefficient 1.55, 95% confidence interval [CI] 0.72-2.38, P < 0.001), not receiving surgical treatment (1.11, 95% CI 0.29-1.93, P = 0.01), not actively employed upon admission (1.47, 95% CI 0.63-2.31, P < 0.01), and self-reported leg-pain recorded 6 weeks posthospital admission (0.49, 95% CI 0.34-0.63, P < 0.001). Interaction analysis showed that the Örebro Musculosceletal Pain Questionnaire had significant prognostic value only on the nonsurgically treated patients (3.26, 95% CI 1.89-4.63, P < 0.001)., Conclusion: The results suggest that a psychosocial screening tool and the implementation of a 6-week postadmission follow-up has prognostic value in the hospital management of severe sciatica., Level of Evidence: 2.

The Dutch Sciatica Trial represents a longitudinal study with complex time-varying confounders as patients with poorer health conditions (e.g. more severe pain) are more likely to opt for surgery, which, in turn, may affect future outcomes (pain severity). A straightforward classical as-treated comparison at the end point would lead to biased estimation of the surgery effect. We present several strategies of causal treatment effect estimation that might be applicable for analyzing such data. These include an inverse probability of treatment weighted regression analysis, a marginal weighted analysis, an unweighted regression analysis, and several propensity score-based approaches. In addition, we demonstrate how to evaluate these approaches in a thorough simulation study where we generate various realistic complex confounding patterns akin to the sciatica study.

The transient receptor potential ankyrin 1 (TRPA1) channel has been implicated in pathophysiological processes that include asthma, cough, and inflammatory pain. Agonists of TRPA1 such as mustard oil and its key component allyl isothiocyanate (AITC) cause pain and neurogenic inflammation in humans and rodents, and TRPA1 antagonists have been reported to be effective in rodent models of pain. In our pursuit of TRPA1 antagonists as potential therapeutics, we generated AMG0902, a potent (IC 90 of 300 nM against rat TRPA1), selective, brain penetrant (brain to plasma ratio of 0.2), and orally bioavailable small molecule TRPA1 antagonist. AMG0902 reduced mechanically evoked C-fiber action potential firing in a skin-nerve preparation from mice previously injected with complete Freund's adjuvant, supporting the role of TRPA1 in inflammatory mechanosensation. In vivo target coverage of TRPA1 by AMG0902 was demonstrated by the prevention of AITC-induced flinching/licking in rats. However, oral administration of AMG0902 to rats resulted in little to no efficacy in models of inflammatory, mechanically evoked hypersensitivity; and no efficacy was observed in a neuropathic pain model. Unbound plasma concentrations achieved in pain models were about 4-fold higher than the IC 90 concentration in the AITC target coverage model, suggesting that either greater target coverage is required for efficacy in the pain models studied or TRPA1 may not contribute significantly to the underlying mechanisms., (© The Author(s) 2016.)

The repeated administration of microglial inhibitor (minocycline) and CCR2 antagonist (RS504393) attenuated the neuropathic pain symptoms in rats following chronic constriction injury of the sciatic nerve, which was associated with decreased spinal microglia activation and the protein level of CCL2 and CCR2. Furthermore, in microglia primary cell cultures minocycline downregulated both CCL2 and CCR2 protein levels after lipopolysaccharide-stimulation. Additionally, in astroglia primary cell cultures minocycline decreased the expression of CCL2, but not CCR2. Our results provide new evidence that modulation of CCL2/CCR2 pathway by microglial inhibitor as well as CCR2 antagonist is effective for neuropathic pain development in rats., (Copyright © 2016 Elsevier B.V. All rights reserved.)

Recent advances in understanding hip joint anatomy and biomechanics have contributed to improvement of diagnosis and treatment decisions for distal causes of deep gluteal syndrome (DGS). Ischiofemoral impingement and hamstrings syndrome are sources of posterior hip pain that can simulate symptoms of DGS. The combination of a comprehensive history and physical examination with imaging and ancillary testing are critical for diagnosis. Six key physical examination tests are described to differentiate distal versus proximal sources of extrapelvic posterior hip pain. Outcomes depend on patient compliance and the understanding of the entire anatomy, biomechanics, clinical presentation, and open versus endoscopic treatment options., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Neuropathic pain is still a basic science and clinical challenge now, the neuronal sensitization and glial activation in the spinal cord (SC) level are more far-reaching for contributing to pain hypersensitivity following chronic constriction injury (CCI). Accumulating evidence indicates that astrocytes and microglia are activated in the spinal cord dorsal horn (SCDH) after CCI. Suppressor of cytokine signaling 1 (SOCS1) plays an important role in regulating of neuronal inflammation. Here, we investigated the role of SOCS1 in SC played in neuropathic pain. We find SOCS1 was persistently downregulated in the spinal neurons after CCI in mice. On the contrary, overexpression of SOCS1 in the SC reversed CCI-induced pain behavioral, activation of neurons, astrocytes, microglia, and the expression of proinflammatory cytokines including tumor necrosis factor α (TNF-α), interleukin 1β (IL-1β) and IL-6. Over all, these results demonstrate that downregulation of SOCS1 contributed to the development and maintenance of neuropathic pain via activating of neurons, astrocytes, microglia, and proinflammatory cytokines. SOCS1 may be developed into a potential target for treating neuropathic pain., (Copyright © 2016 Elsevier Inc. All rights reserved.)

Background: Accumulating evidence indicates that spinal inflammatory and immune responses play an important role in the process of radicular pain caused by intervertebral disk herniation. Resolvin D1 (RvD1) has been shown to have potent antiinflammatory and antinociceptive effects. The current study was undertaken to investigate the analgesic effect of RvD1 and its underlying mechanism in rat models of noncompressive lumbar disk herniation., Methods: Rat models of noncompressive lumber disk herniation were established, and mechanical thresholds were evaluated using the von Frey test during an observation period of 21 days (n = 8/group). Intrathecal injection of vehicle or RvD1 (10 or 100 ng) was performed for three successive postoperative days. On day 7, the ipsilateral spinal dorsal horns and L5 dorsal root ganglions (DRGs) were removed to assess the expressions of tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), IL-10, and transforming growth factor-β1 (TGF-β1) and the activation of nuclear factor-κB (NF-κB)/p65 and phospho-extracellular signal-regulated kinase (p-ERK) signaling (n = 30/group)., Results: The application of nucleus pulposus to L5 DRG induced prolonged mechanical allodynia, inhibited the production of IL-10 and TGF-β1, and up-regulated the expression of TNF-α, IL-1β, NF-κB/p65, and p-ERK in the spinal dorsal horns and DRGs. Intrathecal injection of RvD1 showed a potent analgesic effect, inhibited the up-regulation of TNF-α and IL-1β, increased the release of IL-10 and TGF-β1, and attenuated the expression of NF-κB/p65 and p-ERK in a dose-dependent manner., Conclusions: The current study showed that RvD1 might alleviate neuropathic pain via regulating inflammatory mediators and NF-κB/p65 and p-ERK pathways. Its antiinflammatory and proresolution properties may offer novel therapeutic approaches for the management of neuropathic pain.

Background: Interaction of CD200 with its receptor CD200R has an immunoregulatory role and attenuates various types of neuroinflammatory diseases., Methods: Immunofluorescence staining, western blot analysis, and RT-PCR were used to investigate the modulatory effects of CD200 fusion protein (CD200Fc) on activation of microglia and astrocytes as well as synthesis of pro- (TNF, IL-1β, IL-6) and anti-inflammatory (IL-4, IL-10) cytokines in the L4-L5 spinal cord segments in relation to behavioral signs of neuropathic pain after unilateral sterile chronic constriction injury (sCCI) of the sciatic nerve. Withdrawal thresholds for mechanical hypersensitivity and latencies for thermal hypersensitivity were measured in hind paws 1 day before operation; 1, 3, and 7 days after sCCI operation; and then 5 and 24 h after intrathecal application of artificial cerebrospinal fluid or CD200Fc., Results: Seven days from sCCI operation and 5 h from intrathecal application, CD200Fc reduced mechanical and thermal hypersensitivity when compared with control animals. Simultaneously, CD200Fc attenuated activation of glial cells and decreased proinflammatory and increased anti-inflammatory cytokine messenger RNA (mRNA) levels. Administration of CD200Fc also diminished elevation of CD200 and CD200R proteins as a concomitant reaction of the modulatory system to increased neuroinflammatory reactions after nerve injury. The anti-inflammatory effect of CD200Fc dropped at 24 h after intrathecal application., Conclusions: Intrathecal administration of the CD200R1 agonist CD200Fc induces very rapid suppression of neuroinflammatory reactions associated with glial activation and neuropathic pain development. This may constitute a promising and novel therapeutic approach for the treatment of neuropathic pain.

Background: Common discomforts of pregnancy experienced in the lower extremity include sciatica, leg cramps and varicose veins. Whilst research attention has focused on aetiology and outcomes, the health service utilisation of pregnant women suffering from these complaints has been largely overlooked., Aim: To examine the health status and health service utilisation profile of pregnant women experiencing sciatica, leg cramps or varicose veins., Methods: Linear and logistic regression was applied to a cross-sectional survey of a pregnant women drawn from the 1973 to 1978 cohort (aged 31-36 years in 2009), of the Australian Longitudinal Study on Women's Health (n=1835). Participant's demographics, health status and health service utilisation were compared for all three complaints based upon three subgroups (yes, sought help; yes, did not seek help; no)., Findings: A number of women experienced sciatica (22.1%), leg cramps (18.2%) or varicose veins (9.4%). Of these, a greater proportion of women with sciatica (79.3%) or varicose veins (71.5%) sought help for their condition compared with women with leg cramps (46.7%). Comparisons between women with the conditions of interest who did seek help and those who did not only found that women with a university degree were 0.29 (95% CI: 0.10, 0.85) times less likely to seek help for their condition compared to women with a school only education., Conclusion: Further research examining all health seeking behaviour and treatment use of pregnant women who experience lower extremity problems is required in order to facilitate safe, effective and coordinated maternity care to further support these women during pregnancy., (Copyright © 2015 Australian College of Midwives. Published by Elsevier Ltd. All rights reserved.)

Background: Patients with chronic low back pain and associated radiculopathy present with neuromuscular symptoms both in their lower back and down their leg; however, investigations of muscle activation have so far been isolated to the lower back. During balance perturbations, it is necessary that lower limb muscles activate with proper timing and sequencing along with the lower back musculature to efficiently regain balance control., Methods: Patients with chronic low back pain and radiculopathy and matched controls completed a series of balance perturbations (rapid bilateral arm raise, unanticipated and anticipated sudden loading, and rapid rise to toe). Muscle activation timing and sequencing as well as kinetic response to the perturbations were analyzed., Findings: Patients had significantly delayed lower limb muscle activation in rapid arm raise trials as compared to controls. In sudden loading trials, muscle activation timing was not delayed in patients; however, some differences in posterior chain muscle activation sequencing were present. Patients demonstrated less anterior-posterior movement in unanticipated sudden loading trials, and greater medial-lateral movement in rise to toe trials., Interpretation: Patients with low back pain and radiculopathy demonstrated some significant differences from control participants in terms of muscle activation timing, sequencing, and overall balance control. The presence of differences between patients and controls, specifically in the lower limb, indicates that radiculopathy may play a role in altering balance control in these patients., (Copyright © 2015 Elsevier Ltd. All rights reserved.)

Charcot-Marie-Tooth disease (CMT) is the most commonly inherited peripheral neuropathy. CMT disease signs include distal limb neuropathy, abnormal gait, sensory defects, and deafness. We generated a novel line of CMT2E mice expressing hNF-L(E397K), which displayed muscle atrophy of the lower limbs without denervation, proximal reduction in large caliber axons, and decreased nerve conduction velocity. In this study, we challenged wild type, hNF-L and hNF-L(E397K) mice with crush injury to the sciatic nerve. We analyzed functional recovery by measuring toe spread and analyzed gait using the Catwalk system. hNF-L(E397K) mice demonstrated reduced recovery from nerve injury consistent with increased susceptibility to neuropathy observed in CMT patients. In addition, hNF-L(E397K) developed a permanent reduction in their ability to weight bear, increased mechanical allodynia, and premature gait shift in the injured limb, which led to increasingly disrupted interlimb coordination in hNF-L(E397K). Exacerbation of neuropathy after injury and identification of gait alterations in combination with previously described pathology suggests that hNF-L(E397K) mice recapitulate many of clinical signs associated with CMT2. Therefore, hNF-L(E397K) mice provide a model for determining the efficacy of novel therapies., (Copyright © 2015 Elsevier B.V. All rights reserved.)

Unlabelled: Ultrasound (US) is widely used in rheumatology to study and guide injection of peripheral joints. It can also provide useful information about the anatomy of the lumbar spine. Studies have shown that US examination of the spine was a useful tool to help perform epidural anaesthesia. The purpose of the study was to determine if the selection of the optimum puncture level by US may facilitate epidural steroid injection in case of presumed difficult puncture (BMI>30 kg/m(2), age>60 years or lumbar scoliosis)., Methods: We performed a prospective randomized controlled study. Eighty patients were randomized in two groups: US group (n=40) which underwent a pre-procedure spinal US to determine the optimal lumbar level for injection or control group (n=40) for which the level of injection was determined by palpation. Primary endpoint was the pain during the procedure assessed using the Visual Analogue Scale (VAS)., Results: We found a positive correlation between depth of the epidural space and BMI (P<0.001) and a negative correlation between size of the interspinous spaces and age (P<0.01). Visibility of the epidural space was not altered by obesity or age. We observed a trend toward a reduction in pain intensity during the procedure in the US group compared to the control group with a mean difference at -0.94 [-1.90; 0.02] but the difference was not significant (P=0.054)., Conclusion: US of the lumbar spine was feasible in patients with lumbar conditions even in obese and old ones and allowed the visualization of the epidural space. However, pre-procedure US examination did not reduce pain during the procedure., (Copyright © 2015 Société française de rhumatologie. Published by Elsevier SAS. All rights reserved.)

Whole exome sequencing (WES) is a recently developed technique in genetics research that attempts to identify causative mutations in complex, undiagnosed genetic conditions. Causative mutations are usually identified after filtering the hundreds of variants on WES from an individual's DNA selected by the phenotype. We investigated a patient with a slowly progressive chronic axonal distal motor neuropathy and extrapyramidal syndrome using WES, in whom common genetic mutations had been excluded. Variant filtering identified potentially deleterious mutations in three known disease genes: DCTN1, KIF5A and NEFH, which have been all associated with similar clinical presentations of amyotrophic lateral sclerosis, Parkinsonism and/or hereditary spastic paraplegia. Predicting the functional effect of the mutations were analysed in parallel with detailed clinical investigations. This case highlights the difficulties and pitfalls of applying WES in patients with complex neurological diseases and serves as an instructive tale.

Persistent inflammation results in an increase in the amplitude and duration of depolarization-evoked Ca(2+) transients in putative nociceptive afferents. Previous data indicated that these changes were the result of neither increased neuronal excitability nor an increase in the amplitude of depolarization. Subsequent data also ruled out an increase in voltage-gated Ca(2+) currents and recruitment of Ca(2+)-induced Ca(2+) release. Parametric studies indicated that the inflammation-induced increase in the duration of the evoked Ca(2+) transient required a relatively large and long-lasting increase in the concentration of intracellular Ca(2+) implicating the Na(+)/Ca(2+) exchanger (NCX), a major Ca(2+) extrusion mechanism activated with high intracellular Ca(2+) loads. The contribution of NCX to the inflammation-induced increase in the evoked Ca(2+) transient in rat sensory neurons was tested using fura-2 AM imaging and electrophysiological recordings. Changes in NCX expression and protein were assessed with real-time PCR and Western blot analysis, respectively. An inflammation-induced decrease in NCX activity was observed in a subpopulation of putative nociceptive neurons innervating the site of inflammation. The time course of the decrease in NCX activity paralleled that of the inflammation-induced changes in nociceptive behavior. The change in NCX3 in the cell body was associated with a decrease in NCX3 protein in the ganglia, an increase in the peripheral nerve (sciatic) yet no change in the central root. This single response to inflammation is associated with changes in at least three different segments of the primary afferent, all of which are likely to contribute to the dynamic response to persistent inflammation., (Copyright © 2015 the authors 0270-6474/15/358423-10$15.00/0.)

This study investigated the effects of a single administration of 6-(4-methoxyphenyl)-5-methyl-3-pyridinyl-4-isoxazolo[4,5-c]pyridin-4(5H)-one (MMPIP), a negative allosteric modulator (NAM) of metabotropic glutamate receptor 7 (mGluR7), on pain and on affective and cognitive behavior in neuropathic mice. The activity of pyramidal neurons in the prelimbic cortex (PLC), which respond to stimulation of the basolateral amygdala (BLA) with either excitation or inhibition, was also investigated. The spared nerve injury (SNI) of the sciatic nerve induced, 14 days after surgery, thermal hyperalgesia and mechanical allodynia, reduced open-arm choice in the elevated plus-maze, increased time of immobility in the tail suspension, and increased digging and burying in the marble burying test. Cognitive performance was also significantly compromised in the SNI mice. Spared nerve injury induced phenotypic changes on pyramidal neurons of the PLC; excitatory responses increased, whereas inhibitory responses decreased after BLA stimulation. mGluR7 expression, mainly associated with vesicular glutamate transporter, increased in the hippocampus and decreased in the BLA, PLC, and dorsal raphe in SNI mice. MMPIP increased thermal and mechanical thresholds and open-arm choice. It reduced the immobility in the tail suspension test and the number of marbles buried and of digging events in the marble burying test. MMPIP also improved cognitive performance and restored the balance between excitatory and inhibitory responses of PLC neurons in SNI mice. 7-hydroxy-3-(4-iodophenoxy)-4H-chromen-4-one, XAP044, another selective mGluR7 NAM, reproduced the effects of MMPIP on thermal hyperalgesia, mechanical allodynia, tail suspension, and marble burying test. Altogether, these findings show that mGluR7 NAMs reduce pain responses and affective/cognitive impairments in neuropathic pain conditions.

More than 1.5 billion people worldwide suffer from chronic pain, yet current treatment strategies often lack efficacy or have deleterious side effects in patients. Adenosine is an inhibitory neuromodulator that was previously thought to mediate antinociception through the A1 and A2A receptor subtypes. We have since demonstrated that A3AR agonists have potent analgesic actions in preclinical rodent models of neuropathic pain and that A3AR analgesia is independent of adenosine A1 or A2A unwanted effects. Herein, we explored the contribution of the GABA inhibitory system to A3AR-mediated analgesia using well-characterized mouse and rat models of chronic constriction injury (CCI)-induced neuropathic pain. The deregulation of GABA signaling in pathophysiological pain states is well established: GABA signaling can be hampered by a reduction in extracellular GABA synthesis by GAD65 and enhanced extracellular GABA reuptake via the GABA transporter, GAT-1. In neuropathic pain, GABAAR-mediated signaling can be further disrupted by the loss of the KCC2 chloride anion gradient. Here, we demonstrate that A3AR agonists (IB-MECA and MRS5698) reverse neuropathic pain via a spinal mechanism of action that modulates GABA activity. Spinal administration of the GABAA antagonist, bicuculline, disrupted A3AR-mediated analgesia. Furthermore, A3AR-mediated analgesia was associated with reductions in CCI-related GAD65 and GAT-1 serine dephosphorylation as well as an enhancement of KCC2 serine phosphorylation and activity. Our results suggest that A3AR-mediated reversal of neuropathic pain increases modulation of GABA inhibitory neurotransmission both directly and indirectly through protection of KCC2 function, underscoring the unique utility of A3AR agonists in chronic pain., (Copyright © 2015 the authors 0270-6474/15/356057-11$15.00/0.)

There is increasing evidence that inflammatory (M1-polarized) macrophages drive the nonresolving neuroinflammation that causes neuropathic pain after nerve injury. As interleukin-4 (IL-4) promotes the suppressive (M2-polarized) state in macrophages, we examined whether exploiting an IL-4-mediated pathway could ameliorate M1 macrophage-dependent neuropathic pain. The mRNA and protein expression of IL-4 receptor α chain (IL-4Rα) were upregulated in accumulating F4/80 macrophages in injured sciatic nerve (SCN). In mouse macrophage cell line J774A.1, IL-4 downregulated the mRNA expression of M1 macrophage-specific molecules (IL-1β, CC chemokine ligand 3, and CD86) normally provoked by lipopolysaccharide, while increasing the mRNA expression of M2 macrophage-specific molecules (arginase-1, IL-10, and CD206) through a STAT6-mediated pathway. In ex vivo SCN culture, M1 molecules were highly expressed in the injured SCN on day 7 after partial SCN ligation (PSL) but were decreased by IL-4 treatment. In contrast, M2 molecules were upregulated by IL-4. IL-4 also increased phosphorylated STAT6 (pSTAT6) expression and shifted IL-1β M1 macrophages toward a CD206 M2 phenotype. Perineural administration of IL-4 in mice subject to PSL ameliorated development and maintenance of tactile allodynia and thermal hyperalgesia. These effects of IL-4 were based on that IL-4 treatment increased the proportions of pSTAT6 and CD206 macrophages in injured SCN on day 14 after PSL. We found that neuropathic pain can be ameliorated by IL-4 treatment, which exerts its therapeutic effect on accumulating macrophages through a STAT6-dependent pathway. A shift in macrophage phenotype from the inflammatory to the suppressive phenotype, driven by IL-4R signaling, may have benefits in the treatment of neuropathic pain.

Headache is a potential complication of epidural injection. We report a patient who developed headache 5 days after a lumbar epidural steroid injection, which was not related to the epidural procedure, but caused by Duloxetine induced hyponatremia. Antidepressant drug induced headache should be considered in the differential diagnosis of post dural puncture headache.