Neuropathic pain questionnaires for back pain, what do we know?

INTRODUCTION: Low back pain is a global public health concern, with an estimated lifetime prevalence of 84%. Axial low back pain refers to pain confined to an area in the low back and is different to radicular pain which radiates to extremities. Axial low back pain has traditionally been considered as nociceptive. However, research suggests it may have neuropathic components. Neuropathic axial low back pain is an unresolved, hotly contested topic due to controversies surrounding its aetiology, diagnosis, clinical course, prognosis and treatment options. PURPOSE: The reference standard for diagnosing neuropathic pain is by medical history and clinical assessment (i.e., sensory testing), with optional neuropathic screening tools and selective, further diagnostic tests when clinically needed. Neuropathic screening tools are not always specific for neuropathic radiating low back pain, let alone neuropathic axial low back pain. Additionally, not all have been validated for the English language (e.g., PainDETECT). Research also suggests the percentage of patients identified as having neuropathic radiating low back pain may be dependent on the combination of reference standards used. IMPLICATIONS: There is a need for research that works towards improving understanding of neuropathic axial low back pain and developing a standardised, validated and reliable system for assessing and identifying this condition. This body of research will promote earlier stratification and more rapid referral for appropriate treatment, and improve awareness, assessment and visibility of this condition amongst healthcare practitioners and in healthcare settings. This will lead to transformations in Pathways and health guidelines, ultimately improving patient outcomes.

A Feasibility Study Exploring Measures of Autonomic Function in Patients With Failed Back Surgery Syndrome Undergoing Spinal Cord Stimulation.

OBJECTIVES: Failed back surgery syndrome (FBSS) is associated with impaired autonomic tone, characterized by sympathetic prevalence and vagal withdrawal. Although spinal cord stimulation (SCS) alleviates pain in FBSS, there is limited research investigating how SCS affects measures of autonomic function. This was a prospective, open-label, feasibility study exploring measures of autonomic function in patients with FBSS receiving SCS therapy. MATERIALS AND METHODS: A total of 14 patients with FBSS were recruited for baseline measurements and underwent a trial of 10-kHz SCS. There were three failed trials, resulting in the remaining 11 participants receiving a fully implanted 10-kHz SCS system. One participant requested an explant, resulting in ten participants completing both baseline and follow-up (three to six months after SCS implant) measurements. Autonomic function was assessed using time- and frequency-domain heart rate variability (HRV), baroreceptor reflex sensitivity (BRS), and muscle sympathetic nerve activity (MSNA) using microneurography. Because this was a feasibility study, most of the analysis was descriptive. However, paired t-tests and Wilcoxon signed-rank tests tested for differences between baseline and follow-up. RESULTS: In the whole (N = 14) and final (N = 10) samples, there was between-participant variation in baseline and follow-up measures. This, combined with a small sample, likely contributed to finding no statistically significant differences in any of the measures between baseline and follow-up. However, plotting baseline and follow-up scores for individual participants revealed that those who showed increases in MSNA frequency, square root of the mean of the squared differences between adjacent RR intervals (RMSSD), percentage of the number of RR intervals >50 ms (pRR50), total power, and up BRS between baseline and follow-up had distinct clustering of baseline values compared with those who showed decreases in these measures. CONCLUSIONS: Findings from this feasibility study will aid with informing hypotheses for future research. A key aspect that should be considered in future research concerns exploring the role of baseline measures of autonomic function in influencing change in autonomic function with SCS therapy.

Exploring Patient Satisfaction and Other Outcome Measures With Pain Relief in Spinal Cord Stimulation: A Single-Site, Cohort Audit.

Context Spinal cord stimulation (SCS) is an approved treatment for chronic pain of neuropathic origin. Initial research suggests a close relationship between pain relief and patient satisfaction with SCS. Objectives To see whether similar patterns were observed in our center and to identify areas of improvement, this single-site, cohort audit explored the association between pain relief and satisfaction as well as specific factors that influence satisfaction at follow-up in patients with fully implanted SCS. Methods Age, gender, pain condition, SCS system, average pain (numerical rating scale, NRS), and worst pain (NRS) scores at baseline and the most recent follow-up visit were collected. Percentage change in average pain was calculated, and the patients were allocated to one of three pain improvement groups: <30%, 30%-50%, or >50%. A telephone survey explored patient outcomes including patient satisfaction, sleep, fatigue, quality of life (QoL), walking ability, and medication use. Chi-square tests of independence were performed. Results The final sample comprised 87 patients (<30%: n = 26; 30%-50%: n = 29; >50%: n = 32). The pain improvement group was significantly associated with satisfaction (p = 0.010): all patients in the >50% improvement group reported being either very satisfied or somewhat satisfied with SCS. The pain improvement group was also significantly associated with change in sleep (p < 0.001), fatigue (p = 0.001), QoL (p = 0.003), and opioid consumption (p = 0.010). Improvements were most frequently reported in the >50% improvement group. Conclusion Findings point to an association between pain relief and patient satisfaction with SCS. Other factors, including sleep, fatigue, QoL, and opioid consumption, may influence this association and deserve further exploration.

A case series of new radicular pain following the insertion of spinal cord stimulator.

Purpose: Although spinal cord stimulation (SCS) is a safe procedure, equipment-related, biological and neurological complications have been observed in previous research, particularly case reports. No reports of new neuropathic pain in the absence of neurological deficit or positive MRI findings have been described. We detail three cases of new-onset radicular pain in the L5/S1 dermatome following insertion of SCS. Methods: This was a retrospective case series of three patients. Details of clinical background, indications for SCS and events occurring during insertion and further management were recorded. Results: All three cases were technically difficult and required multiple epidural entry levels, with repeated passage of the electrode into and within the epidural space. All cases involved accessing epidural space T12/L1 and L1/L2. A possible explanation for the new-onset radicular pain could concern oedema to the conus medullaris, resulting from repeated passage of the electrode at the T12/L1 level. Alternative explanations could be direct trauma to transiting nerve roots, neuroplastic changes resulting in peripheral and central sensitisation and immune-mediated nerve injury. Conclusion: MRI imaging should be analysed prior to the SCS procedure to identify the level of the conus medullaris, with the aim of avoiding repeated passage of electrodes at that level. Unintended neurological adverse events should be discussed with patients during the consent process. Careful patient selection and psychological screening may also help identify patients who may be unlikely to respond to SCS therapy. Further reporting of new radiculopathic pain following SCS insertion is required to strengthen understanding of its potential causes.

A prospective long-term follow-up of dorsal root ganglion stimulation for the management of chronic intractable pain.

ABSTRACT: Initial clinical studies have shown that the stimulation of the dorsal root ganglion (DRG) can significantly reduce chronic intractable pain. However, clinical data on long-term results and complications of these systems are limited. The aim of this prospective study is to report on a single center long-term follow-up of DRG stimulation for intractable chronic pain. Participants were implanted with DRG stimulation devices between 2013 and 2015 with an observation period of 24 months. Patients were contacted again in 2020 for a final follow-up (ie, between 5 and 7 years postimplantation). Forty-two participants were recruited, of whom 32 received the fully implantable pulse generator (IPG). At the final follow-up, 50% (16/32) of participants were still using DRG stimulation. Two participants still had the original IPG and 14 had received a replacement IPG. Pain scores were significantly reduced at 24 months, mean difference 1.7 (95% confidence interval: 0.2-3.3, P = 0.03), and at the last follow-up, mean difference 2.1 (95% confidence interval: 0.3-4, P = 0.03). Significant improvements were observed for health-related quality of life. The findings were generally robust to imputation methods of missing data. Implantable pulse generators of 8 patients were explanted because of dissatisfaction with pain relief. In conclusion, DRG stimulation can provide effective pain relief and improved quality of life in patients suffering with neuropathic pain, although this study had a revision rate of 42% within the first 24 months, and 56% of IPGs that were replaced because of battery depletion had a shorter than expected battery life.

Men and Women Respond Equally Well to Spinal Cord and Dorsal Root Ganglion Stimulation.

OBJECTIVES: The influence of gender on outcomes in individuals undergoing treatment for chronic pain is unclear. This retrospective, single-site study explored the impact of gender on pain, quality of life (QoL), revisions, and explants in patients with failed back surgery syndrome or visceral pain, who received a fully implanted 10 kHz spinal cord stimulation (SCS), burst SCS, or dorsal root ganglion (DRG) stimulation system. MATERIALS AND METHODS: The following data were collected from paper and electronic records: gender, age, chronic pain diagnosis, system, baseline and follow-up scores (average pain [visual analog scale, VAS], worst pain [VAS], QoL [EQ-5D-3L]), revisions, and explants. Data were statistically analyzed by one-way ANCOVAs controlling for age, chi-square tests of independence, and logistic regression. RESULTS: The final sample comprised 387 patients (176 males and 211 females). Males were significantly older compared to females (mean difference: 2.33 years, p = 0.044). Controlling for age, baseline average pain was significantly lower in males than females (mean difference: -0.32, p = 0.049). Males and females responded equally well to 10 kHz SCS and burst SCS as well as DRG stimulation. A greater percentage of males (5%) than females (1%) had revisions due to lead fractures. Additionally, more females (13%) than males (6%) had an explant due to insufficient pain relief. Female gender and older age were associated with greater likelihood of having an explant compared to male gender and younger age. CONCLUSION: Gender may play an influential role in pain severity at baseline but have little effect at follow-up. To help identify which patients may undergo a revision or explant, gender and age could be important factors and should be further scrutinized. Even though men and women responded equally well to SCS and DRG stimulation, more men had a revision due to lead fractures, and more women were explanted due to insufficient pain relief.

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.

Pain Relief and Safety Outcomes with Cervical 10 kHz Spinal Cord Stimulation: Systematic Literature Review and Meta-analysis.

BACKGROUND: Chronic pain in head, neck, shoulders and upper limbs is debilitating, and patients usually rely on pain medications or surgery to manage their symptoms. However, given the current opioid epidemic, non-pharmacological interventions that reduce pain, such as spinal cord stimulation (SCS), are needed. The purpose of this study was to review the evidence on paresthesia-free 10 kHz SCS therapy for neck and upper extremity pain. METHODS: Systematic literature search was performed for studies reporting outcomes for cervical 10 kHz SCS using date limits from May 2008 to November 2020. The study results were analyzed and described qualitatively. Additionally, when feasible, meta-analyses of the outcome data, with 95% confidence intervals (CIs), were conducted using both the fixed-effects (FE) and random-effects (RE) models. RESULTS: A total of 15 studies were eligible for inclusion. The proportion of patients who achieved ≥ 50% pain reduction was 83% (95% CI 77-89%) in both the FE and RE models. The proportion of patients who reduced/eliminated their opioid consumption was 39% (95% CI 31-46%) in the FE model and 39% (95% CI 31-48%) in the RE model. Pain or discomfort with the implant, lead migration, and infections were potential risks following cervical SCS. Explant rate was 0.1 (95% CI 0.0-0.2) events per 100 person-months, and no patients in the included studies experienced a neurological complication or paresthesia. CONCLUSION: Findings suggest 10 kHz SCS is a promising, safe, minimally invasive alternative for managing chronic upper limb and neck pain.

Efficacy and Safety of 10 kHz Spinal Cord Stimulation for the Treatment of Chronic Pain: A Systematic Review and Narrative Synthesis of Real-World Retrospective Studies.

10 kHz spinal cord stimulation (SCS) is increasingly utilized globally to treat chronic pain syndromes. Real-world evidence complementing randomized controlled trials supporting its use, has accumulated over the last decade. This systematic review aims to summarize the retrospective literature with reference to the efficacy and safety of 10 kHz SCS. We performed a systematic literature search of PubMed between 1 January 2009 and 21 August 2020 for English-language retrospective studies of ≥3 human subjects implanted with a Senza® 10 kHz SCS system and followed-up for ≥3 months. Two independent reviewers screened titles/abstracts of 327 studies and 46 full-text manuscripts. In total, 16 articles were eligible for inclusion; 15 reported effectiveness outcomes and 11 presented safety outcomes. Follow-up duration ranged from 6-34 months. Mean pain relief was >50% in most studies, regardless of follow-up duration. Responder rates ranged from 67-100% at ≤12 months follow-up, and from 46-76% thereafter. 32-71% of patients decreased opioid or nonopioid analgesia intake. Complication incidence rates were consistent with other published SCS literature. Findings suggest 10 kHz SCS provides safe and durable pain relief in pragmatic populations of chronic pain patients. Furthermore, it may decrease opioid requirements, highlighting the key role 10 kHz SCS can play in the medium-term management of chronic pain.

An Open-Label Pilot Study Investigating Noninvasive High-Frequency Peripheral Nerve Fiber Stimulation in Chronic Pain.

OBJECTIVE: Providing sustained and effective treatment via the peripheral nervous system for the management of chronic pain is challenging. Application of noninvasive high-frequency stimulation at or near the painful area may benefit those with chronic pain. This open-label pilot survey examined the impact of this stimulation on pain intensity, activities of daily living, functional capacity, and medication consumption after 2 weeks of treatment. METHODS: Stimulation was administered at home using the summation of two high-frequency sinusoidal alternating signals at 3858 and 3980 Hz delivered between two electrodes placed directly over one or two locations of pain. Individuals completed a survey after 2 weeks to assess pain, activities of daily living (ADL), pain medication consumption, quality of life (QoL), mood, sleep, functional outcomes, and satisfaction. RESULTS: 463 individuals (372 males; 91 females) retuned the completed survey after 2 weeks of treatment. Pain and ADL scores significantly improved at follow-up compared with baseline (pain mean difference: 3.05; 95% confidence interval [CI]: 2.86, 3.24; ADL mean difference: 1.82; 95% CI: 1.60, 2.04). Corresponding improvements in QoL, sleep, mood, functional outcomes, and satisfaction were noted. On average, 8.00 ± 11.11 hours of pain relief were reported with 54% experiencing reductions in pain medication consumption. 98% would use the stimulation in the future. CONCLUSION: Two weeks of noninvasive high-frequency peripheral nerve fiber stimulation appeared to confer positive effects in individuals with chronic pain. Future research employing a control group/arm is needed to establish the long-term impact of this bioelectric technique in specific pain cohorts.

One-Year Results of Prospective Research Study Using 10 kHz Spinal Cord Stimulation in Persistent Nonoperated Low Back Pain of Neuropathic Origin: Maiden Back Study.

PURPOSE: Spinal cord stimulation (SCS) is a recommended treatment for chronic neuropathic pain. Persistent nonoperative low back pain of neuropathic origin has profound negative impacts on patient's lives. This prospective, open label, research study aimed to explore the use of SCS in patients with associated features of central sensitisation such as allodynia and hyperalgesia. MATERIALS AND METHODS: Twenty-one patients with back pain and hyperalgesia or allodynia who had not had prior spinal surgery underwent a SCS trial followed by full implantation. SCS comprised administering electrical impulses epidurally at a frequency of 10 kHz and pulse width of 30 µsec. Patients attended follow-up visits after 6 and 12 months of SCS. Repeated measure ANOVAs/Friedman tests explored change after 6 and 12 months of 10 kHz SCS. Independent sample t-tests/Mann-Whitney U tests examined differences in response after 12 months of 10 kHz SCS. RESULTS: Back and leg pain, quality of life (QoL), pain-related disability, and morphine equivalence significantly improved compared with baseline following 6 and 12 months of 10 kHz SCS. There were no increases in the consumption of opioids, amitriptyline, gabapentin or pregabalin in any patient. After 12 months of treatment, 52% encountered ≥50% improvement in back pain, 44% achieved remission (0-3 cm back pain VAS), 40% reported ODI scores between 0 and 40 and 60% experienced a reduction of at least 10 ODI points. Patients reporting ≥10-point improvement in ODI had significantly longer pain history durations and experienced significantly greater improvements in back pain, leg pain and QoL than those reporting <10-point improvement in ODI. CONCLUSION: The 10 kHz SCS improved back and leg pain, QoL, pain-related disability and medication consumption in patients with nonoperative back pain of neuropathic origin. With further research incorporating a sham control arm, the efficacy of 10 kHz SCS in this patient cohort will become more established.

Mediation of Cardiac Macrophage Activity via Auricular Vagal Nerve Stimulation Ameliorates Cardiac Ischemia/Reperfusion Injury.

BACKGROUND: Myocardial infarction (MI) reperfusion therapy causes paradoxical cardiac complications. Following restoration of blood flow to infarcted regions, a multitude of inflammatory cells are recruited to the site of injury for tissue repair. Continual progression of cardiac inflammatory responses does, however, lead to adverse cardiac remodeling, inevitably causing heart failure. MAIN BODY: Increasing evidence of the cardioprotective effects of both invasive and non-invasive vagal nerve stimulation (VNS) suggests that these may be feasible methods to treat myocardial ischemia/reperfusion injury via anti-inflammatory regulation. The mechanisms through which auricular VNS controls inflammation are yet to be explored. In this review, we discuss the potential of autonomic nervous system modulation, particularly via the parasympathetic branch, in ameliorating MI. Novel insights are provided about the activation of the cholinergic anti-inflammatory pathway on cardiac macrophages. Acetylcholine binding to the α7 nicotinic acetylcholine receptor (α7nAChR) expressed on macrophages polarizes the pro-inflammatory into anti-inflammatory subtypes. Activation of the α7nAChR stimulates the signal transducer and activator of transcription 3 (STAT3) signaling pathway. This inhibits the secretion of pro-inflammatory cytokines, limiting ischemic injury in the myocardium and initiating efficient reparative mechanisms. We highlight recent developments in the controversial auricular vagal neuro-circuitry and how they may relate to activation of the cholinergic anti-inflammatory pathway. CONCLUSION: Emerging published data suggest that auricular VNS is an inexpensive healthcare modality, mediating the dynamic balance between pro- and anti-inflammatory responses in cardiac macrophages and ameliorating cardiac ischemia/reperfusion injury.

Pocket pain, does location matter: a single-centre retrospective study of patients implanted with a spinal cord stimulator.

OBJECTIVES: Spinal cord stimulation (SCS) is an effective therapy for alleviating pain but reported complication rates vary between healthcare centers. This study explored the prevalence of pain associated with Implantable Pulse Generators (IPGs), the component that powers the SCS system. METHODS: This was a retrospective, single site study analyzing data from 764 patients who had a fully implanted SCS between September 2013 and March 2020. Demographic data were collected together with IPG site and type, patient reported presence of IPG site pain, revisions, explants and baseline scores for neuropathic pain (using the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs questionnaire). Data were statistically analyzed by one-way analysis of variance, independent sample t-tests, X2 tests of independence and logistic regression modeling. RESULTS: IPG site pain occurred in 127 (17%) of 764 patients. These patients had higher baseline neuropathic pain scores than those who reported no IPG site pain. This complication was more common in females than males. The lowest rates of IPG site pain occurred after posterior chest wall placement and the highest rates occurred after abdominal implants. 7% of patients had revision surgery for IPG site pain (n=55) and 10 of 95 explanted patients stated that IPG site pain was a secondary influencing factor. CONCLUSIONS: These findings suggest that IPG site pain is a common complication, contributing to SCS revisions and explantation. This study shows that anatomical factors and baseline characteristics of individual patients may contribute to IPG site pain and indicates that exploration of potential factors leading to IPG revision is required.

BurstDR spinal cord stimulation in the treatment of chronic visceral pain.

Background:Visceral pain can be disabling for patients and challenging to treat in the clinic. Spinal cord stimulation is a NICE approved treatment for chronic neuropathic pain, presenting potential advantages over conventional therapies for managing chronic visceral pain. Results: A retrospective study revealed that a specific type of spinal cord stimulation, BurstDRTM (Abbott, TX, USA), was effective at improving pain and quality of life in patients with chronic visceral pain. Baseline pain scores significantly correlated with change at follow-up, suggesting it may be possible to identify potential responders from the outset. BurstDR was safe: rates of revision, explantation and complications were low. Conclusion: Clinical trials exploring the long-term effects of BurstDR including a control arm are needed. Findings could have the potential to inform best practice and improve outcomes for individuals with chronic visceral pain.

Effects of transcutaneous vagus nerve stimulation in individuals aged 55 years or above: potential benefits of daily stimulation.

Ageing is associated with attenuated autonomic function. Transcutaneous vagal nerve stimulation (tVNS) improved autonomic function in healthy young participants. We therefore investigated the effects of a single session of tVNS (studies 1 and 2) and tVNS administered daily for two weeks (study 3) in volunteers aged ≥ 55 years. tVNS was performed using modified surface electrodes on the tragus and connected to a transcutaneous electrical nerve stimulation (TENS) machine. Study 1: participants (n=14) received a single session of tVNS and sham. Study 2: all participants (n=51) underwent a single session of tVNS. Study 3: participants (n=29) received daily tVNS for two weeks. Heart rate variability and baroreflex sensitivity were derived. Quality of life (QoL), mood and sleep were assessed in study 3. tVNS promoted increases in measures of vagal tone and was associated with greater increases in baroreflex sensitivity than sham. Two weeks of daily tVNS improved measures of autonomic function, and some aspects of QoL, mood and sleep. Importantly, findings showed that improvements in measures of autonomic balance were more pronounced in participants with greater baseline sympathetic prevalence. This suggests it may be possible to identify individuals who are likely to encounter significant benefits from tVNS.