Multipronged effects of increased screen time on the nutritional imbalance: A cross-sectional study of students of Amritsar aged 6-16 years.

Background: Intense marketing of fast-food items impacts the eating habits among children and adolescents. Various studies suggest that increased screen time leads to increased fast-food consumption and decreased sleep duration, both of which are linked to obesity in growing age. Objectives: To assess screen time and dietary habits among the study group and to estimate their effect on sleep deprivation and obesity. Methods: This cross-sectional study was conducted from January 2019 to December 2019 in three schools in Amritsar selected by lottery method of simple random sampling. Out of 4,226 students, 355 overweight and obese students were interviewed regarding their dietary habits. An informed written assent was taken from the mothers. The information was collected on a semi-structured, pre-designed questionnaire by interviewing the mothers of students between 6 and 11 years of age and the students of 12-16 years. Results: 94.4% of students preferred fast foods to regular meals and 58.3% were in the habit of skipping breakfast. 59.4% had a history of daily intake of fast foods while 76.1% had a habit of consuming fast foods while watching television. Only 31.7% had an adequate sleeping pattern of 9-11 hours and 79.7% of the students had a screen time of over 3 hours. Conclusions: More the screen time, the more the chances of missing meals. Being awake for a long odd time leads to increased consumption of foods/snacks furthermore. Regarding the harmful effects of fast foods, the source of information was from schools, but only 41.4% were aware about these effects.

Chemotherapy for pain: reversing inflammatory and neuropathic pain with the anticancer agent mithramycin A.

ABSTRACT: The persistence of inflammatory and neuropathic pain is poorly understood. We investigated a novel therapeutic paradigm by targeting gene networks that sustain or reverse persistent pain states. Our prior observations found that Sp1-like transcription factors drive the expression of TRPV1, a pain receptor, that is blocked in vitro by mithramycin A (MTM), an inhibitor of Sp1-like factors. Here, we investigate the ability of MTM to reverse in vivo models of inflammatory and chemotherapy-induced peripheral neuropathy (CIPN) pain and explore MTM's underlying mechanisms. Mithramycin reversed inflammatory heat hyperalgesia induced by complete Freund adjuvant and cisplatin-induced heat and mechanical hypersensitivity. In addition, MTM reversed both short-term and long-term (1 month) oxaliplatin-induced mechanical and cold hypersensitivity, without the rescue of intraepidermal nerve fiber loss. Mithramycin reversed oxaliplatin-induced cold hypersensitivity and oxaliplatin-induced TRPM8 overexpression in dorsal root ganglion (DRG). Evidence across multiple transcriptomic profiling approaches suggest that MTM reverses inflammatory and neuropathic pain through broad transcriptional and alternative splicing regulatory actions. Mithramycin-dependent changes in gene expression following oxaliplatin treatment were largely opposite to and rarely overlapped with changes in gene expression induced by oxaliplatin alone. Notably, RNAseq analysis revealed MTM rescue of oxaliplatin-induced dysregulation of mitochondrial electron transport chain genes that correlated with in vivo reversal of excess reactive oxygen species in DRG neurons. This finding suggests that the mechanism(s) driving persistent pain states such as CIPN are not fixed but are sustained by ongoing modifiable transcription-dependent processes.

Restorative neurostimulation for chronic mechanical low back pain - Three year results from the United Kingdom post market clinical follow-up registry.

Introduction: Mechanical chronic low back pain is often associated with impaired neuromuscular control of the lumbar multifidus muscles, the most important stabilizers of the lumbar spine. Restorative neurostimulation is a modality for the treatment for this specific subset of patients aimed to facilitate restoration of neuromuscular control by bilateral stimulation of the L2 medial branches. Evidence from both prospective and randomised clinical trials to date has demonstrated substantial improvements in clinical outcomes such as pain, disability and health-related quality of life. Methods: This study is an open label prospective follow-up for the treatment of chronic mechanical low back pain of nociceptive origin with restorative neurostimulation. Patients completed assessments for pain, disability and health-related quality of life. Outcomes were collected at 45, 90 and 180 days, and 1, 2 and 3 years after the activation visit. Results: Forty-two patients were implanted with the device and 33 (79%) were available at the 3-year appointment. Patients in this cohort presented with severe chronic low back pain (NRS = 7.0 ± 0.2) and severe disability (ODI 46.6 ± 12.0). The health-related quality of life was also severely impacted at baseline (EQ-5D 0.426 ± 0.061). Changes in pain, disability and quality of life at three-year follow-up demonstrated a statistically significant improvement between baseline and 1, 2 and 3 years. After 3 years of therapy, average NRS scores had reduced to 2.7± 0.3 and mean ODI score to 26.0 ± 3.1 while EQ-5D-5L index improved to 0.707 ± 0.036. Conclusions: The ongoing follow-up of this post market cohort continues to demonstrate that restorative neurostimulation provides a statistically significant, clinically meaningful and durable response across pain, disability and quality-of life scores for patients suffering chronic mechanical low back pain that has been refractory to conventional management. Trial Registration: ClinicalTrials.gov Identifier: NCT01985230.

Pulse Intensity Effects of Burst and Tonic Spinal Cord Stimulation on Neural Responses to Brushing in Patients With Neuropathic Pain.

OBJECTIVES: Tonic spinal cord stimulation (SCS) is accompanied by paresthesia in affected body regions. Comparatively, the absence of paresthesia with burst SCS suggests different involvement of the dorsal column system conveying afferent impulses from low-threshold mechanoreceptors. This study evaluated cortical activation changes during gentle brushing of a pain-free leg during four SCS pulse intensities to assess the effect of intensity on recruitment of dorsal column system fibers during burst and tonic SCS. MATERIALS AND METHODS: Twenty patients using SCS (11 burst, nine tonic) for neuropathic leg pain participated. Brushing was administered to a pain-free area of the leg during four SCS intensities: therapeutic (100%), medium (66%), low (33%), and no stimulation. Whole-brain electroencephalography was continuously recorded. Changes in spectral power during brushing were evaluated using the event-related desynchronization (ERD) method in theta (4-7 Hz), alpha (8-13 Hz), and beta (16-24 Hz) frequency bands. RESULTS: Brushing was accompanied by a suppression of cortical oscillations in the range 4-24 Hz. Stronger intensities of burst and tonic SCS led to less suppression of 4-7 Hz and 8-13 Hz bands in parietal electrodes, and in central electrodes in the 16-24 Hz band, with the strongest, statistically significant suppression at medium intensity. Tonic SCS showed a stronger reduction in 4-7 Hz oscillations over right sensorimotor electrodes, and over right frontal and left sensorimotor electrodes in the 8-13 Hz band, compared to burst SCS. CONCLUSIONS: Results suggest that burst and tonic SCS are mediated by both different and shared mechanisms. Attenuated brushing-related ERD with tonic SCS suggests a gating of cortical activation by afferent impulses in the dorsal column, whereas burst may engage different pathways. Diminished brushing-related ERD at medium and therapeutic intensities of burst and tonic SCS points towards a nonlinear effect of SCS on somatosensory processing.

Real world experience with minimally invasive wireless percutaneous neuromodulation in a tertiary care centre.

Background: Wireless percutaneous nerve stimulation (PNS) for chronic pain is rapidly evolving in the ever expanding neuromodulation paradigm. Safety and lower risks with a potential of long-term analgesia cannot be over emphasised especially with the ongoing opioid pandemic. PNS with an implanted pulse generator (IPG) has also been shown to provide good benefit, without often unpleasant widespread paraesthesia from conventional spinal cord stimulators. Aim and Methods: We retrospectively extracted data on all wireless PNS implants in our highly specialised pain neuromodulation centre since initiation of wireless PNS service in August 2019. Patient demographics, pain history, analgesic intake and details on implant follow-up data within 1 year post-implant including pain relief, EuroQol-5 Dimension (EQ-5D) and Patients' Global Impression of Change (PGIC) scores were extracted. The cases are presented in a narrative format. Result: A total of five patients were implanted with wireless (Stimwave®) PNS from August 2019 to February 2020. Neuropathic pain was the most common presenting diagnosis. All patients showed >50% pain relief at 3 months. EQ-5D and PGIC did not show any improvement in the subjects. Two of the patients managed to decrease their analgesics after implantation. Similar sustained benefits could not be demonstrated after 1 year. Discussion: PNS can provide analgesia in appropriately selected cases. Naivety of the technique and procedure might cause some degree of uncertainty. External pulse generator with wireless transmission avoids IPG and tunnelling related side effects, but requires individualised special wearable technology to power the lead. Minimally invasive nature of the technique might be attractive and preferable for patients with complex medical issues, nickel allergy and poor general health who may otherwise be unsuitable for Spinal Cord Stimulation (SCS) with conventional hardware. Robust prospective controlled studies and RCTs in future might provide further insights on utility in other neuropathic pain diagnosis, long-term outcomes and acceptability compared to conventional SCS.

Percutaneous cervical cordotomy for cancer-related pain: prospective multimodal outcomes evaluation.

BACKGROUND: Percutaneous cervical cordotomy (PCC) offers pain relief to patients with unilateral treatment-refractory cancer-related pain. There is insufficient evidence about any effects of this intervention on patients' quality of life. METHOD: Comprehensive multimodal assessment to determine how PCC affects pain, analgesic intake and quality of life of patients with medically refractory, unilateral cancer-related pain.This study was set in a multidisciplinary, tertiary cancer pain service. Patient outcomes immediately following PCC were prospectively recorded. Patients were also followed up at 4 weeks. RESULTS: Outcome variables collected included: background and breakthrough pain numerical rating scores before PCC, at discharge and 4 weeks postprocedure; oral morphine equivalent opioid dose changes, Patient's Global Impression of Change, Eastern Cooperative oncology group performance status and health related quality of life score, that is, EuroQol-5 dimension-5 level (EQ-5D). CONCLUSIONS: Despite significant improvement in pain and other standard outcomes sustained at 4 weeks, there was little evidence of improvement in EQ-5D scores. In patients with terminal cancer, improved pain levels following cordotomy for cancer-related pain does not appear to translate into improvements in overall quality of life as assessed with the generic EQ-5D measure.

Mechanistically informed non-invasive peripheral nerve stimulation for peripheral neuropathic pain: a randomised double-blind sham-controlled trial.

BACKGROUND: Induction of long-term synaptic depression (LTD) is proposed as a treatment mechanism for chronic pain but remains untested in clinical populations. Two interlinked studies; (1) A patient-assessor blinded, randomised, sham-controlled clinical trial and (2) an open-label mechanistic study, sought to examine therapeutic LTD for persons with chronic peripheral nerve injury pain. METHODS: (1) Patients were randomised using a concealed, computer-generated schedule to either active or sham non-invasive low-frequency nerve stimulation (LFS), for 3 months (minimum 10 min/day). The primary outcome was average pain intensity (0-10 Likert scale) recorded over 1 week, at 3 months, compared between study groups. (2) On trial completion, consenting subjects entered a mechanistic study assessing somatosensory changes in response to LFS. RESULTS: (1) 76 patients were randomised (38 per group), with 65 (31 active, 34 sham) included in the intention to treat analysis. The primary outcome was not significant, pain scores were 0.3 units lower in active group (95% CI - 1.0, 0.3; p = 0.30) giving an effect size of 0.19 (Cohen's D). Two non-device related serious adverse events were reported. (2) In the mechanistic study (n = 19) primary outcomes of mechanical pain sensitivity (p = 0.006) and dynamic mechanical allodynia (p = 0.043) significantly improved indicating reduced mechanical hyperalgesia. CONCLUSIONS: Results from the RCT failed to reach significance. Results from the mechanistic study provide new evidence for effective induction of LTD in a clinical population. Taken together results add to mechanistic understanding of LTD and help inform future study design and approaches to treatment. Trial registration ISRCTN53432663.

Restorative Neurostimulation for Chronic Mechanical Low Back Pain: Results from a Prospective Multi-centre Longitudinal Cohort.

INTRODUCTION: Low back pain impacts most people throughout the course of their lives and contributes significantly to the global burden of disease. In some patients, symptoms resolve with little intervention, while others are amenable to surgical intervention, some cases are intractable to current care paradigms. Restorative neurostimulation is an emerging therapy for chronic mechanical low back pain. METHODS: We conducted a prospective post-market follow-up of 42 patients treated for longstanding chronic mechanical low back pain with restorative neurostimulation. Patients were followed up at 45, 90, and 180 days and 1 and 2 years following activation of the device. Pain, disability, and health-related quality of life were recorded. RESULTS: Among the 37 patients completing 2-year follow-up, numerical rating scale (NRS) pain scores improved from 7.0 ± 0.2 to 3.5 ± 0.3 (p < 0.001), Oswestry Disability Index (ODI) scores improved from 46.2 ± 2.2 to 29.2 ± 3.1 (p < 0.001), and health-related quality of life (measured by the EuroQol 5-Dimension 5-Level questionnaire-EQ-5D-5L) improved from 0.426 ± 0.035 to 0.675 ± 0.030 (p < 0.001). Additionally, 57% of patients experienced a greater than 50% reduction in pain, and 51% of patients benefited by a greater than 15-point reduction in ODI, both substantial improvements. CONCLUSION: This real-world sample of patients shows that restorative neurostimulation can provide substantial and durable benefit to a cohort of patients that have traditionally had few reliable treatment options. Our findings support the continued used of this therapy in well-selected patients. TRIAL REGISTRATION: ClinicalTrials.gov Identifier: NCT01985230.

The goal of this study was to examine the effectiveness of restorative neurostimulation for the treatment of patients with chronic mechanical low back pain. This technique has been studied in a clinical trial setting and been shown to be both safe and effective. This study reports on the real-world experience from five sites in the United Kingdom. Patients with a history of severe low back pain that lasted on average for more than 13 years were implanted with a nerve stimulation device that targets the nerves that control important spinal stabilising muscles. All of the patients were asked to perform two stimulation sessions per day for 30 min each. Over the next 2 years, patients reported substantial reductions in pain and disability and an improvement in health-related quality of life. The safety profile of the therapy was excellent when compared to similar minimally invasive therapies for different spine pathologies. In this difficult-to-treat patient population who have few remaining therapeutic options, restorative neurostimulation is a valuable tool in the clinician's armamentarium.

Radiofrequency denervation of the lumbar facet joints: guidelines for the RADICAL randomised controlled trial.

BACKGROUND AND AIM: The RADICAL trial has been funded by the National Institute for Health Research (NIHR) to evaluate the clinical and cost-effectiveness of radiofrequency denervation (RFD) for low back pain. Recommendations have been published which aim to standardise selection of patients and RFD technique. However, it is important to ensure these recommendations are acceptable to clinicians within the context of the trial. The aim of this work was to develop standardised criteria for the trial entry and RFD technique for implementation within the RADICAL trial. METHODS: Fourteen pain clinicians completed a survey, which involved reviewing the current recommendations and indicating whether they disagreed with any of the recommendations and if so why. Responses were collated and presented at a half-day workshop with 14 attendees. During the workshop, the National Low Back and Radicular Pain Pathway (NLBRPP) guidelines for patient selection and an article by Eldabe and colleagues presenting recommendations on the RFD technique were reviewed. Attendees discussed whether each component of the recommendations should be mandatory, mandatory with alteration or clarification or optional within the RADICAL trial. RESULTS: Attendees agreed during the workshop that 5 of the 10 criteria for patient selection described in the NLBRPP should be mandatory within the RADICAL trial. Three were agreed as mandatory criteria but required further clarification, one of which involved defining a positive response to a diagnostic medial branch block as ⩾60% pain relief. Two criteria had optional components. After reviewing the recommendations on the RFD technique from Eldabe and colleagues, seven components were agreed as mandatory, three were mandatory with alterations and three were optional. CONCLUSION: When evaluating complex interventions, such as RFD, it is important to ensure agreement and clarity on the clinical protocol, so that the intervention can be reproduced, if found to be effective.

The impact of the COVID-19 pandemic on patients awaiting spinal cord stimulation surgery in the United Kingdom: a multi-centre patient survey.

INTRODUCTION: Spinal cord stimulation (SCS) is a recommended treatment for chronic refractory neuropathic pain. During the COVID-19 pandemic, elective procedures have been postponed indefinitely both to provide capacity to deal with the emergency caseload and to avoid exposure of elective patients to COVID-19. This survey aimed to explore the effect of the pandemic on chronic pain in this group and the views of patients towards undergoing SCS treatment when routine services should resume. METHODS: This was a prospective, multi-centre telephone patient survey that analysed data from 330 patients with chronic pain who were on an SCS waiting list. Questions focussed on severity of pain, effect on mental health, medication consumption and reliance on support networks during the COVID-19 pandemic. Views towards undergoing SCS therapy were also ascertained. Counts and percentages were generated, and chi-square tests of independence explored the impact of COVID-19 risk (very high, high, low) on survey responses. RESULTS: Pain, mental health and patient's ability to self-manage pain deteriorated in around 47%, 50% and 38% of patients, respectively. Some patients reported increases in pain medication consumption (37%) and reliance on support network (41%). Patients showed a willingness to attend for COVID-19 testing (92%), self-isolate prior to SCS (94%) and undergo the procedure as soon as possible (76%). CONCLUSION: Our findings suggest that even during the COVID-19 pandemic, there remains a strong clinical need for patients with chronic pain identified as likely SCS responders to be treated quickly. The current prioritisation of new SCS at category 4 (delayed more than 3 months) is challenged judging by this national survey. These patients are awaiting SCS surgery to relieve severe intractable neuropathic pain. A priority at category 3 (delayed up to 3 months) or in some selected cases, at category 2 are the appropriate priority categories.

Technical challenges of performing S1 root block: role for double needle and multilevel needle technique.

INTRODUCTION: S1 root block is performed for pain in the lower limbs due to S1 nerve root inflammation at the L5/S1 disc level or compression in the lateral recess. We often note anterior or posterior spread of contrast away from the L5/S1 disc through an anatomically appropriate needle tip placement. We frequently encounter vascular spread when performing S1 root blocks, and the reported incidence varies between 10.4% and 27.8%. There is no clear strategy published to manage these challenges. In such clinical scenarios, we propose a double needle and/or a multilevel needle technique. CASE: A 39-year-old male presented with radicular pain in the left S1 distribution which matched the magnetic resonance imaging (MRI) scan findings and thus he was listed for a left S1 root block. A 22G needle was placed at the S1 level and upon injecting the contrast, vascular spread and anterior and distal spread along the nerve root were noted and the contrast did not reach the site of the pathology, the L5/S1 disc. The contrast continued to spread anteriorly despite withdrawing the needle. A second needle was placed medial and inferior to the first needle and the contrast spread now was adequate, that is, towards the L5/S1 disc and thus the injection was accomplished in a safe and satisfactory manner without needing to reschedule the procedure. CONCLUSION: Double needle technique can assist in overcoming problems encountered when performing an S1 root block. The alternatives could be the multilevel technique or to reschedule the procedure or consider a less optimal technique such as a caudal or a lumbar interlaminar epidural. In this technical report, we have highlighted various intervention options to mitigate such challenges and included a flow diagram to assist in decision-making. We have also discussed the possibility of altering the consent to accommodate the changes to the planned procedure.

Surgical microdiscectomy versus transforaminal epidural steroid injection in patients with sciatica secondary to herniated lumbar disc (NERVES): a phase 3, multicentre, open-label, randomised controlled trial and economic evaluation.

BACKGROUND: The optimal invasive treatment for sciatica secondary to herniated lumbar disc remains controversial, with a paucity of evidence for use of non-surgical treatments such as transforaminal epidural steroid injection (TFESI) over surgical microdiscectomy. We aimed to investigate the clinical and cost-effectiveness of these options for management of radicular pain secondary to herniated lumbar disc. METHODS: We did a pragmatic, multicentre, phase 3, open-label, randomised controlled trial at 11 spinal units across the UK. Eligible patients were aged 16-65 years, had MRI-confirmed non-emergency sciatica secondary to herniated lumbar disc with symptom duration between 6 weeks and 12 months, and had leg pain that was not responsive to non-invasive management. Participants were randomly assigned (1:1) to receive either TFESI or surgical microdiscectomy by an online randomisation system that was stratified by centre with random permuted blocks. The primary outcome was Oswestry Disability Questionnaire (ODQ) score at 18 weeks. All randomly assigned participants who completed a valid ODQ at baseline and at 18 weeks were included in the analysis. Safety analysis included all treated participants. Cost-effectiveness was estimated from the EuroQol-5D-5L, Hospital Episode Statistics, medication usage, and self-reported resource-use data. This trial was registered with ISRCTN, number ISRCTN04820368, and EudraCT, number 2014-002751-25. FINDINGS: Between March 6, 2015, and Dec 21, 2017, 163 (15%) of 1055 screened patients were enrolled, with 80 participants (49%) randomly assigned to the TFESI group and 83 participants (51%) to the surgery group. At week 18, ODQ scores were 30·02 (SD 24·38) for 63 assessed patients in the TFESI group and 22·30 (19·83) for 61 assessed patients in the surgery group. Mean improvement was 24·52 points (18·89) for the TFESI group and 26·74 points (21·35) for the surgery group, with an estimated treatment difference of -4·25 (95% CI -11·09 to 2·59; p=0·22). There were four serious adverse events in four participants associated with surgery, and none with TFESI. Compared with TFESI, surgery had an incremental cost-effectiveness ratio of £38 737 per quality-adjusted life-year gained, and a 0·17 probability of being cost-effective at a willingness-to-pay threshold of £20 000 per quality-adjusted life-year. INTERPRETATION: For patients with sciatica secondary to herniated lumbar disc, with symptom duration of up to 12 months, TFESI should be considered as a first invasive treatment option. Surgery is unlikely to be a cost-effective alternative to TFESI. FUNDING: Health Technology Assessment programme of the National Institute for Health Research (NIHR), UK.

Microdiscectomy compared with transforaminal epidural steroid injection for persistent radicular pain caused by prolapsed intervertebral disc: the NERVES RCT.

BACKGROUND: Sciatica is a common condition reported to affect > 3% of the UK population at any time and is most often caused by a prolapsed intervertebral disc. Currently, there is no uniformly adopted treatment strategy. Invasive treatments, such as surgery (i.e. microdiscectomy) and transforaminal epidural steroid injection, are often reserved for failed conservative treatment. OBJECTIVE: To compare the clinical effectiveness and cost-effectiveness of microdiscectomy with transforaminal epidural steroid injection for the management of radicular pain secondary to lumbar prolapsed intervertebral disc for non-emergency presentation of sciatica of < 12 months' duration. INTERVENTIONS: Patients were randomised to either (1) microdiscectomy or (2) transforaminal epidural steroid injection. DESIGN: A pragmatic, multicentre, randomised prospective trial comparing microdiscectomy with transforaminal epidural steroid injection for sciatica due to prolapsed intervertebral disc with < 1 year symptom duration. SETTING: NHS services providing secondary spinal surgical care within the UK. PARTICIPANTS: A total of 163 participants (aged 16-65 years) were recruited from 11 UK NHS outpatient clinics. MAIN OUTCOME MEASURES: The primary outcome was participant-completed Oswestry Disability Questionnaire score at 18 weeks post randomisation. Secondary outcomes were visual analogue scores for leg pain and back pain; modified Roland-Morris score (for sciatica), Core Outcome Measures Index score and participant satisfaction at 12-weekly intervals. Cost-effectiveness and quality of life were assessed using the EuroQol-5 Dimensions, five-level version; Hospital Episode Statistics data; medication usage; and self-reported cost data at 12-weekly intervals. Adverse event data were collected. The economic outcome was incremental cost per quality-adjusted life-year gained from the perspective of the NHS in England. RESULTS: Eighty-three participants were allocated to transforaminal epidural steroid injection and 80 participants were allocated to microdiscectomy, using an online randomisation system. At week 18, Oswestry Disability Questionnaire scores had decreased, relative to baseline, by 26.7 points in the microdiscectomy group and by 24.5 points in the transforaminal epidural steroid injection. The difference between the treatments was not statistically significant (estimated treatment effect -4.25 points, 95% confidence interval -11.09 to 2.59 points). Nor were there significant differences between treatments in any of the secondary outcomes: Oswestry Disability Questionnaire scores, visual analogue scores for leg pain and back pain, modified Roland-Morris score and Core Outcome Measures Index score up to 54 weeks. There were four (3.8%) serious adverse events in the microdiscectomy group, including one nerve palsy (foot drop), and none in the transforaminal epidural steroid injection group. Compared with transforaminal epidural steroid injection, microdiscectomy had an incremental cost-effectiveness ratio of £38,737 per quality-adjusted life-year gained and a probability of 0.17 of being cost-effective at a willingness to pay threshold of £20,000 per quality-adjusted life-year. LIMITATIONS: Primary outcome data was invalid or incomplete for 24% of participants. Sensitivity analyses demonstrated robustness to assumptions made regarding missing data. Eighteen per cent of participants in the transforaminal epidural steroid injection group subsequently received microdiscectomy prior to their primary outcome assessment. CONCLUSIONS: To the best of our knowledge, the NErve Root Block VErsus Surgery trial is the first trial to evaluate the comparative clinical effectiveness and cost-effectiveness of microdiscectomy and transforaminal epidural steroid injection. No statistically significant difference was found between the two treatments for the primary outcome. It is unlikely that microdiscectomy is cost-effective compared with transforaminal epidural steroid injection at a threshold of £20,000 per quality-adjusted life-year for sciatica secondary to prolapsed intervertebral disc. FUTURE WORK: These results will lead to further studies in the streamlining and earlier management of discogenic sciatica. TRIAL REGISTRATION: Current Controlled Trials ISRCTN04820368 and EudraCT 2014-002751-25. FUNDING: This project was funded by the National Institute for Health Research (NIHR) Health Technology Assessment programme and will be published in full in Health Technology Assessment; Vol. 25, No. 24. See the NIHR Journals Library website for further project information.

WHAT IS THE PROBLEM?: Sciatica or pain related to nerve irritation travelling down the leg is common in young working adults and most likely to be caused by a 'slipped' (prolapsed) disc. Although the majority of cases get better on their own and within 4­6 weeks, a significant group of patients struggle with disabling symptoms sometimes beyond 1 year. Consequently, patients struggle to maintain their home and working lives. Many treatments are available for sciatica, but simpler treatments (e.g. pain tablets, physiotherapy and changing one's lifestyle) are often not very effective and patients have often tried all of them by the time they are seen in hospital to have tests, such as scans, done. Surgery to remove part of the disc is recommended in cases where the pain is accompanied by severe weakness in one or both legs, or where doctors think that nerves may be damaged because patients have bladder, bowel and sexual functioning difficulties (i.e. red flag symptoms). Surgery works well in alleviation of referred leg pain and also to relieve pressure on a physically compressed nerve that may be showing clinical sign of injury/weakness. An alternative to surgery is to inject a mixture of anaesthetic and steroid close to the site of the disc injury and nerve, but at the moment we do not know whether or not these injections work in the long term. They are cheaper and less invasive, with fewer risks than surgery, such as from anaesthetic or infection. WHAT DID OUR STUDY INVESTIGATE?: This study compared the usefulness of surgery with injections for patients who have had sciatica for < 1 year and who have tried simple remedies but are still in pain. Patients were allocated to have either surgery or the injection. Symptoms (e.g. pain) were assessed after 18 weeks. WHAT DID WE FIND?: We found that there was no significant difference between surgery and injection at the primary end point. Surgery was not significantly different from injection in terms of clinical outcome and was not cost-effective compared with injection. OUR CONCLUSION AND RECOMMENDATION: Given the cost of surgery and the risks to patients, we suggest that further studies should be carried out to explore whether or not all patients with sciatica due to a slipped disc should be considered suitable for an injection, unless there is a good reason not to.

Epidural Interventions in the Management of Chronic Spinal Pain: American Society of Interventional Pain Physicians (ASIPP) Comprehensive Evidence-Based Guidelines.

BACKGROUND: Chronic spinal pain is the most prevalent chronic disease with employment of multiple modes of interventional techniques including epidural interventions. Multiple randomized controlled trials (RCTs), observational studies, systematic reviews, and guidelines have been published. The recent review of the utilization patterns and expenditures show that there has been a decline in utilization of epidural injections with decrease in inflation adjusted costs from 2009 to 2018. The American Society of Interventional Pain Physicians (ASIPP) published guidelines for interventional techniques in 2013, and guidelines for facet joint interventions in 2020. Consequently, these guidelines have been prepared to update previously existing guidelines. OBJECTIVE: To provide evidence-based guidance in performing therapeutic epidural procedures, including caudal, interlaminar in lumbar, cervical, and thoracic spinal regions, transforaminal in lumbar spine, and percutaneous adhesiolysis in the lumbar spine. METHODS: The methodology utilized included the development of objective and key questions with utilization of trustworthy standards. The literature pertaining to all aspects of epidural interventions was viewed with best evidence synthesis of available literature and  recommendations were provided. RESULTS: In preparation of the guidelines, extensive literature review was performed. In addition to review of multiple manuscripts in reference to utilization, expenditures, anatomical and pathophysiological considerations, pharmacological and harmful effects of drugs and procedures, for evidence synthesis we have included 47 systematic reviews and 43 RCTs covering all epidural interventions to meet the objectives.The evidence recommendations are as follows: Disc herniation: Based on relevant, high-quality fluoroscopically guided epidural injections, with or without steroids, and results of previous systematic reviews, the evidence is Level I for caudal epidural injections, lumbar interlaminar epidural injections, lumbar transforaminal epidural injections, and cervical interlaminar epidural injections with strong recommendation for long-term effectiveness.The evidence for percutaneous adhesiolysis in managing disc herniation based on one high-quality, placebo-controlled RCT is Level II with moderate to strong recommendation for long-term improvement in patients nonresponsive to conservative management and fluoroscopically guided epidural injections. For thoracic disc herniation, based on one relevant, high-quality RCT of thoracic epidural with fluoroscopic guidance, with or without steroids, the evidence is Level II with moderate to strong recommendation for long-term effectiveness.Spinal stenosis: The evidence based on one high-quality RCT in each category the evidence is Level III to II for fluoroscopically guided caudal epidural injections with moderate to strong recommendation and Level II for fluoroscopically guided lumbar and cervical interlaminar epidural injections with moderate to strong recommendation for long-term effectiveness.The evidence for lumbar transforaminal epidural injections is Level IV to III with moderate recommendation with fluoroscopically guided lumbar transforaminal epidural injections for long-term improvement. The evidence for percutaneous adhesiolysis in lumbar stenosis based on relevant, moderate to high quality RCTs, observational studies, and systematic reviews is Level II with moderate to strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. Axial discogenic pain: The evidence for axial discogenic pain without facet joint pain or sacroiliac joint pain in the lumbar and cervical spine with fluoroscopically guided caudal, lumbar and cervical interlaminar epidural injections, based on one relevant high quality RCT in each category is Level II with moderate to strong recommendation for long-term improvement, with or without steroids. Post-surgery syndrome: The evidence for lumbar and cervical post-surgery syndrome based on one relevant, high-quality RCT with fluoroscopic guidance for caudal and cervical interlaminar epidural injections, with or without steroids, is Level II with moderate to strong recommendation for long-term improvement. For percutaneous adhesiolysis, based on multiple moderate to high-quality RCTs and systematic reviews, the evidence is Level I with strong recommendation for long-term improvement after failure of conservative management and fluoroscopically guided epidural injections. LIMITATIONS: The limitations of these guidelines include a continued paucity of high-quality studies for some techniques and various conditions including spinal stenosis, post-surgery syndrome, and discogenic pain. CONCLUSIONS: These epidural intervention guidelines including percutaneous adhesiolysis were prepared with a comprehensive review of the literature with methodologic quality assessment and determination of level of evidence with strength of recommendations.

Interventional Pain Medicine Practice in the UK and the USA: A Survey of 242 Pain Physicians.

BACKGROUND: Pain medicine practices vary across different regions within a country and between countries. OBJECTIVES: The objective of the survey was to study the variation in interventional pain medicine practices in the United Kingdom (UK) and the United States (US). METHODS: A survey was designed in 2019 on Survey Monkey®. Pain physicians from the UK and the US were invited to respond. RESULTS: A total of 120 responses were received from pain physicians in the UK and 122 from the US. Twenty-six percent and 90% of pain physicians in the UK and US, respectively, are in full-time pain medicine practice. There was marked variation in the utilization of diagnostic medial branch blocks before performing radiofrequency denervation (RFD) between the UK and the US. In the UK, 42% of pain physicians, and 50% in the US, use a 20-gauge or a 22-gauge radiofrequency needle for lumbar RFD. Around 30% to 50% of pain physicians, both in the UK and the US, discontinued antithrombotic agents before medial branch blocks at all the spinal levels. Around 50% of pain physicians in the UK and US are stopping anticoagulants before lumbar and cervical RFD. Over 95% of UK and US respondents stopped antithrombotic agents for interlaminar and transforaminal epidural injections along the spine. At the lumbar level, 51% of pain physicians in the UK and 47% in the US use a particulate steroid for the initial lumbar transforaminal epidural injection (TFESI); and 4% and 14% in the UK and US, respectively, use a particulate steroid for initial cervical TFESI. Eight percent of pain physicians in the UK and 20% from the US would switch to a particulate steroid if the initial TFESI with a nonparticulate steroid did not provide satisfactory pain relief. Ten percent of pain physicians from the United Kingdom and 20% from the US believed that this switch provides better pain relief. LIMITATIONS: Interventional pain physicians from the UK and the US were invited to respond. This may not reflect global practice. CONCLUSIONS: Our survey has highlighted the wide variation in interventional pain medicine practices both in the UK and the US. The relevant governing bodies in the UK and in the US should encourage clinicians to use at least an 18-gauge radiofrequency needle for RFD at the lumbar level. Discontinuing antithrombotic agents for the lumbar medial branch block is not justifiable. Pain physicians must discuss the advantages and disadvantages of using a nonparticulate over a particulate steroid preparation with the patient before performing TFESI as a standard procedure during the consenting process. KEY WORDS: Antithrombotic agents, epidural steroid, medial branch blocks, pain practice variations, particulate and nonparticulate steroids, radiofrequency denervation, spinal interventions.

Percutaneous cervical cordotomy for cancer-related pain: national data.

OBJECTIVES: Percutaneous cervical cordotomy (PCC) is an interventional ablative procedure in the armamentarium for cancer pain treatment, but there is limited evidence to support its use. This study aimed to assess the effectiveness and safety of PCC. METHODS: Analysis was undertaken of the first national (UK) prospective data repository of adult patients with cancer undergoing PCC for pain treatment. The relationship between pain and other outcomes before and after PCC was examined using appropriate statistical methods. RESULTS: Data on 159 patients' PCCs (performed from 1 January 2012 to 6 June 2017 in three centres) were assessed: median (IQR) age was 66 (58-71) years, 47 (30%) were female. Mesothelioma was the most common primary malignancy (57%). The median (IQR) time from cancer diagnosis to PCC assessment was 13.3 (6.2-23.2) months; PCC to follow-up was 9 (8-25) days; and survival after PCC was 1.3 (0.6-2.8) months. The mean (SD) for 'average pain' using a numerical rating scale was 6 (2) before PCC and 2 (2) at follow-up, and for 'worst pain' 9 (1) and 3 (3), respectively. The median (IQR) reduction in strong opioid dose at follow-up was 50% (34-50). With the exception of 'activity', all health-related quality of life scores (5-level version of EuroQol-5 Dimension) either improved or were stable after PCC. Six patients (4%) had PCC-related adverse events. CONCLUSIONS: PCC is an effective treatment for cancer pain; however, findings in this study suggest PCC referrals tended to be late in patients' disease trajectories. Further study into earlier treatment and seeking international consensus on PCC outcomes will further enhance opportunities to improve patient care.

Spinal signalling of C-fiber mediated pleasant touch in humans.

C-tactile afferents form a distinct channel that encodes pleasant tactile stimulation. Prevailing views indicate they project, as with other unmyelinated afferents, in lamina I-spinothalamic pathways. However, we found that spinothalamic ablation in humans, whilst profoundly impairing pain, temperature and itch, had no effect on pleasant touch perception. Only discriminative touch deficits were seen. These findings preclude privileged C-tactile-lamina I-spinothalamic projections and imply integrated hedonic and discriminative spinal processing from the body.

Transcription factor Sp4 is required for hyperalgesic state persistence.

Understanding how painful hypersensitive states develop and persist beyond the initial hours to days is critically important in the effort to devise strategies to prevent and/or reverse chronic painful states. Changes in nociceptor transcription can alter the abundance of nociceptive signaling elements, resulting in longer-term change in nociceptor phenotype. As a result, sensitized nociceptive signaling can be further amplified and nocifensive behaviors sustained for weeks to months. Building on our previous finding that transcription factor Sp4 positively regulates the expression of the pain transducing channel TRPV1 in Dorsal Root Ganglion (DRG) neurons, we sought to determine if Sp4 serves a broader role in the development and persistence of hypersensitive states in mice. We observed that more than 90% of Sp4 staining DRG neurons were small to medium sized, primarily unmyelinated (NF200 neg) and the majority co-expressed nociceptor markers TRPV1 and/or isolectin B4 (IB4). Genetically modified mice (Sp4+/-) with a 50% reduction of Sp4 showed a reduction in DRG TRPV1 mRNA and neuronal responses to the TRPV1 agonist-capsaicin. Importantly, Sp4+/- mice failed to develop persistent inflammatory thermal hyperalgesia, showing a reversal to control values after 6 hours. Despite a reversal of inflammatory thermal hyperalgesia, there was no difference in CFA-induced hindpaw swelling between CFA Sp4+/- and CFA wild type mice. Similarly, Sp4+/- mice failed to develop persistent mechanical hypersensitivity to hind-paw injection of NGF. Although Sp4+/- mice developed hypersensitivity to traumatic nerve injury, Sp4+/- mice failed to develop persistent cold or mechanical hypersensitivity to the platinum-based chemotherapeutic agent oxaliplatin, a non-traumatic model of neuropathic pain. Overall, Sp4+/- mice displayed a remarkable ability to reverse the development of multiple models of persistent inflammatory and neuropathic hypersensitivity. This suggests that Sp4 functions as a critical control point for a network of genes that conspire in the persistence of painful hypersensitive states.