Quantitative Sensory Testing in Spinal Cord Stimulation: A Narrative Review.

OBJECTIVES: Quantitative sensory testing (QST) has been used for decades to study sensory abnormalities in multiple conditions in which the somatosensory system is compromised, including pain. It is commonly used in pharmacologic studies on chronic pain but less so in conjunction with neuromodulation. This review aims to assess the utility of QST in spinal cord stimulation (SCS) protocols. MATERIALS AND METHODS: For this narrative review, we searched PubMed for records of studies in which sensory testing has been performed as part of a clinical study on SCS from 1975 onward until October 2023. We focused on studies in which QST has been used to explore the effect of SCS on neuropathic, neuropathic-like, or mixed pain. RESULTS: Our search identified 22 useful studies, all small and exploratory, using heterogeneous methods. Four studies used the full battery of validated German Research Network on Neuropathic Pain QST. There is emerging evidence that assessment dynamic mechanical allodynia (eight studies), and mechanical/thermal temporal summation of pain (eight studies) may have a role in quantifying the response to various SCS waveforms. There also were sporadic reports of improvement of sensory deficits in a proportion of patients with neuropathic pain that warrant further study. CONCLUSIONS: We recommend the adoption of QST into future clinical research protocols, using either the full QST protocol or a less time-demanding short-form QST.

Effects of Lockdown Restrictions and Impact of Anxiety and Depression Symptoms in People With Chronic Pain During the Covid-19 Pandemic: A 13-Wave Longitudinal Study.

In early 2020, countries across the world imposed lockdown restrictions to curb the spread of the Covid-19 coronavirus. Lockdown conditions, including social and physical distancing measures and recommended self-isolation for clinically vulnerable groups, were proposed to disproportionately affect those living with chronic pain, who already report reduced access to social support and increased isolation. Yet, empirical evidence from longitudinal studies tracking the effects of prolonged and fluctuating lockdown conditions, and potential psychological factors mediating the effects of such restrictions on outcomes in chronic pain populations, is lacking. Accordingly, in the present 13-wave longitudinal study, we surveyed pain intensity, pain interference, and tiredness in people with chronic pain over the course of 11 months of the Covid-19 pandemic (April 2020-March 2021). Of N = 431 participants at baseline, average completion rate was ∼50% of time points, and all available data points were included in linear mixed models. We examined the impact of varying levels of lockdown restrictions on these outcomes and investigated whether psychological distress levels mediated effects. We found that a full national lockdown was related to greater pain intensity, and these effects were partially mediated by depressive symptoms. No effects of lockdown level were found for pain interference and tiredness, which were instead predicted by higher levels of depression, anxiety, pain catastrophising, and reduced exercise. Our findings are relevant for improving patient care in current and future crises. Offering remote management options for low mood could be particularly beneficial for this vulnerable population in the event of future implementation of lockdown restrictions. PERSPECTIVE: This longitudinal study demonstrates the impact of Covid-19 lockdown restrictions on people with chronic pain. Findings suggest a complex interaction of psychosocial factors that impacted various aspects of pain experience in patients, which offer the potential to inform clinical strategies for remote medicine and future crises.

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.

Adverse effects of COVID-19-related lockdown on pain, physical activity and psychological well-being in people with chronic pain.

Countries across the world imposed lockdown restrictions during the COVID-19 pandemic. It has been proposed that lockdown conditions, including social and physical distancing measures, may disproportionately impact those living with chronic pain and require rapid adaptation to treatment and care strategies. Using an online methodology, we investigated how lockdown restrictions in the United Kingdom impacted individuals with chronic pain (N = 431) relative to a healthy control group (N = 88). Data were collected during the most stringent period of lockdown in the United Kingdom (mid-April to early-May 2020). In accordance with the fear-avoidance model, we hypothesised lockdown-related increases in pain and psychological distress, which would be mediated by levels of pain catastrophising. Responses indicated that people with chronic pain perceived increased pain severity, compared to their estimation of typical pain levels prior to lockdown (p < .001). They were also more adversely affected by lockdown conditions compared to pain-free individuals, demonstrating greater self-perceived increases in anxiety and depressed mood, increased loneliness and reduced levels of physical exercise (p ⩽ .001). Hierarchical regression analysis revealed that pain catastrophising was an important factor relating to the extent of self-perceived increases in pain severity during lockdown (ß = .27, p < .001) and also mediated the relationship between decreased mood and pain. Perceived decreases in levels of physical exercise also related to perceptions of increased pain (ß = .15, p < .001). Interestingly, levels of pain intensity (measured at two time points at pre and during lockdown) in a subgroup (N = 85) did not demonstrate a significant change. However, individuals in this subgroup still reported self-perceived pain increases during lockdown, which were also predicted by baseline levels of pain catastrophising. Overall, the findings indicate that people with chronic pain suffer adverse effects of lockdown including self-perceived increases in their pain. Remote pain management provision to target reduction of pain catastrophising and increase health behaviours including physical activity could be beneficial for this vulnerable population.

Research design considerations for randomized controlled trials of spinal cord stimulation for pain: Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials/Institute of Neuromodulation/International Neuromodulation Society recommendations.

ABSTRACT: Spinal cord stimulation (SCS) is an interventional nonpharmacologic treatment used for chronic pain and other indications. Methods for evaluating the safety and efficacy of SCS have evolved from uncontrolled and retrospective studies to prospective randomized controlled trials (RCTs). Although randomization overcomes certain types of bias, additional challenges to the validity of RCTs of SCS include blinding, choice of control groups, nonspecific effects of treatment variables (eg, paresthesia, device programming and recharging, psychological support, and rehabilitative techniques), and safety considerations. To address these challenges, 3 professional societies (Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials, Institute of Neuromodulation, and International Neuromodulation Society) convened a meeting to develop consensus recommendations on the design, conduct, analysis, and interpretation of RCTs of SCS for chronic pain. This article summarizes the results of this meeting. Highlights of our recommendations include disclosing all funding source and potential conflicts; incorporating mechanistic objectives when possible; avoiding noninferiority designs without internal demonstration of assay sensitivity; achieving and documenting double-blinding whenever possible; documenting investigator and site experience; keeping all information provided to patients balanced with respect to expectation of benefit; disclosing all information provided to patients, including verbal scripts; using placebo/sham controls when possible; capturing a complete set of outcome assessments; accounting for ancillary pharmacologic and nonpharmacologic treatments in a clear manner; providing a complete description of intended and actual programming interactions; making a prospective ascertainment of SCS-specific safety outcomes; training patients and researchers on appropriate expectations, outcome assessments, and other key aspects of study performance; and providing transparent and complete reporting of results according to applicable reporting guidelines.

Advances in diagnosis, classification, pathophysiology, and management of trigeminal neuralgia.

Trigeminal neuralgia is a very painful neurological condition with severe, stimulus-evoked, short-lasting stabbing pain attacks in the face. The past decade has offered new insights into trigeminal neuralgia symptomatology, pathophysiology, and treatment, leading to a change in the classification of the condition. An accurate diagnosis is crucial because neuroimaging interpretation and clinical management differ among the various forms of facial pain. MRI using specific sequences should be a part of the diagnostic workup to detect a possible neurovascular contact and exclude secondary causes. Demonstration of a neurovascular contact should not be used to confirm a diagnosis but rather to facilitate surgical decision making. Carbamazepine and oxcarbazepine are drugs of first choice for long-term treatment, whereas microvascular decompression is the first-line surgery in medically refractory patients. Advances in neuroimaging techniques and animal models will provide further insight into the causes of trigeminal neuralgia and its pathophysiology. Development of more efficacious treatment options is highly warranted.

PULSE-I - Is rePetitive Upper Limb SEnsory stimulation early after stroke feasible and acceptable? A stratified single-blinded randomised controlled feasibility study.

BACKGROUND: Reduction in sensorimotor function of the upper limb is a common and persistent impairment after stroke, and less than half of stroke survivors recover even basic function of the upper limb after a year. Previous work in stroke has shown that repetitive sensory stimulation (RSS) of the upper limb may benefit motor function. As yet, there have been no investigations of RSS in the early-acute period despite this being the time window during which the neuroplastic processes underpinning sensorimotor recovery are likely to occur. METHODS: A single-blinded, stratified, randomised controlled feasibility study was undertaken at two NHS acute trusts to determine the recruitment rate, intervention adherence, and safety and acceptability of an RSS intervention in the early period after stroke. Participants were recruited within 2 weeks of index stroke. Stratified on arm function, they were randomised to receive either 45 min of daily RSS and usual care or usual care alone (UC) for 2 weeks. Changes from baseline on the primary outcome of the Action Research Arm Test (ARAT) to measurements taken by a blinded assessor were examined after completion of the intervention (2 weeks) and at 3 months from randomisation. RESULTS: Forty patients were recruited and randomised (RSS n = 23; UC n = 17) with a recruitment rate of 9.5% (40/417) of patients admitted with a stroke of which 52 (12.5%) were potentially eligible, with 10 declining to participate for various reasons. Participants found the RSS intervention acceptable and adherence was good. The intervention was safe and there were no serious adverse events. CONCLUSIONS: This study indicates that recruitment to a trial of RSS in the acute period after stroke is feasible. The intervention was well tolerated and appeared to provide additional benefit to usual care. In addition to a definitive trial of efficacy, further work is warranted to examine the effects of varying doses of RSS upon arm function and the mechanism by which RSS induces sensorimotor recovery in the acute period after stroke. TRIAL REGISTRATION: ISRCTN, registry no: ISRCTN17422343 ; IRAS Project ID: 215137. Registered on October 2016.

The IASP classification of chronic pain for ICD-11: chronic neuropathic pain.

The upcoming 11th revision of the International Statistical Classification of Diseases and Related Health Problems (ICD) of the World Health Organization (WHO) offers a unique opportunity to improve the representation of painful disorders. For this purpose, the International Association for the Study of Pain (IASP) has convened an interdisciplinary task force of pain specialists. Here, we present the case for a reclassification of nervous system lesions or diseases associated with persistent or recurrent pain for ≥3 months. The new classification lists the most common conditions of peripheral neuropathic pain: trigeminal neuralgia, peripheral nerve injury, painful polyneuropathy, postherpetic neuralgia, and painful radiculopathy. Conditions of central neuropathic pain include pain caused by spinal cord or brain injury, poststroke pain, and pain associated with multiple sclerosis. Diseases not explicitly mentioned in the classification are captured in residual categories of ICD-11. Conditions of chronic neuropathic pain are either insufficiently defined or missing in the current version of the ICD, despite their prevalence and clinical importance. We provide the short definitions of diagnostic entities for which we submitted more detailed content models to the WHO. Definitions and content models were established in collaboration with the Classification Committee of the IASP's Neuropathic Pain Special Interest Group (NeuPSIG). Up to 10% of the general population experience neuropathic pain. The majority of these patients do not receive satisfactory relief with existing treatments. A precise classification of chronic neuropathic pain in ICD-11 is necessary to document this public health need and the therapeutic challenges related to chronic neuropathic pain.

Patient-delivered tDCS on chronic neuropathic pain in prior responders to TMS (a randomized controlled pilot study).

BACKGROUND: Successful response to repetitive transcranial magnetic stimulation (rTMS) of the motor cortex requires continued maintenance treatments. Transcranial Direct Current Stimulation (tDCS) may provide a more convenient alternative. METHODS: This pilot study aimed to examine the feasibility of a randomized, double-blind, double-crossover pilot study for patients to self-administer tDCS motor cortex stimulation for 20 minutes/day over five consecutive days. Primary outcomes were as follows: usability of patient-administered tDCS, compliance with device, recruitment, and retention rates. Secondary outcomes were as follows: effect on overall pain levels and quality of life via Short Form-36 anxiety and depression via Hospital Anxiety and Depression Scale, and Mini-Mental State scores. RESULTS: A total of 24 subjects with neuropathic pain, who had previously experienced rTMS motor cortex stimulation (13 with reduction in pain scores, 11 nonresponders) were recruited at the Pain Research Institute, Fazakerley, UK. A total of 21 subjects completed the study. Recruitment rate was 100% but retention rate was only 87.5%. All patients reported satisfactory usability of the tDCS device. No significant difference was shown between Sham vs Anodal (-0.16, 95% CI: -0.43 to 0.11) P=0.43, Sham vs Cathodal (0.11, 95% CI: -0.16 to 0.37) P=0.94, or Cathodal vs Anodal (-0.27, 95% CI: -0.54 to 0.00) P=0.053 treatments. Furthermore, no significant changes were demonstrated in anxiety, depression, or quality of life measurements. The data collected to estimate sample size for a definitive study suggested that the study's sample size was already large enough to detect a change of 15% in pain levels at 90% power for the overall group of 21 patients. CONCLUSION: This study did not show a beneficial effect of tDCS in this group of patients and does not support the need for a larger definitive study using the same experimental paradigm. TRIAL REGISTRATION: ISRCTN56839387.

Triggering trigeminal neuralgia.

Introduction Although it is widely accepted that facial pain paroxysms triggered by innocuous stimuli constitute a hallmark sign of trigeminal neuralgia, very few studies to date have systematically investigated the role of the triggers involved. In the recently published diagnostic classification, triggered pain is an essential criterion for the diagnosis of trigeminal neuralgia but no study to date has been designed to address this issue directly. In this study, we set out to determine, in patients with trigeminal neuralgia, how frequently triggers are present, which manoeuvres activate them and where cutaneous and mucosal trigger zones are located. Methods Clinical characteristics focusing on trigger factors were collected from 140 patients with trigeminal neuralgia, in a cross-sectional study design. Results Provocation of paroxysmal pain by various trigger manoeuvres was reported by 136 of the 140 patients. The most frequent manoeuvres were gentle touching of the face (79%) and talking (54%). Trigger zones were predominantly reported in the perioral and nasal region. Conclusion This study confirms that in trigeminal neuralgia, paroxysmal pain is associated with triggers in virtually all patients and supports the use of triggers as an essential diagnostic feature of trigeminal neuralgia.

Capsaicin 8% Patch Repeat Treatment in Nondiabetic Peripheral Neuropathic Pain: A 52-Week, Open-Label, Single-Arm, Safety Study.

OBJECTIVES: To investigate the long-term safety and tolerability of capsaicin 8% patch repeat treatment in nondiabetic patients with peripheral neuropathic pain. METHODS: A prospective, open-label, observational study in patients with postherpetic neuralgia, posttraumatic or postsurgical nerve injury, HIV-associated distal sensory polyneuropathy, or other peripheral neuropathic pain, and average daily pain score ≥4, who received ≤6 capsaicin 8% patch treatments over 52 weeks according to clinical need (retreatment at 9 to 12 wk intervals). Sensory testing and analgesic effectiveness were assessed using "bedside tests" and Brief Pain Inventory (question 5). RESULTS: Overall, 306 patients received treatment. Treatment-emergent adverse events (TEAEs) and drug-related TEAEs were reported by 252 (82.4%) and 207 (67.6%) patients. Application site pain was the most common drug-related TEAE (n=112, 36.6%); no drug-related serious TEAEs were reported. Sensory category shift analyses from baseline to end of study (EoS) in patients attending at least 2 sensory visits (n=278 for all tests except warm, n=277) found sensory deterioration/loss in at least 1 modality in 50.4% (n=140); deterioration/loss in 1, 2, 3, 4, or 5 modalities occurred in 26.6% (n=74), 14.0% (n=39), 5.8% (n=16), 2.5% (n=7), and 1.4% (n=4) cases. Newly emergent hyperesthesia or allodynia was apparent in 1.1% to 3.6% of the cases (depending on modality) by EoS. Between 25.2% and 32.0% of patients reported improvement in a sensory modality by EoS. Average daily pain was 6.6 and 4.7 at baseline and month 12. CONCLUSIONS: Generally, capsaicin 8% patch repeat treatment over 52 weeks was well tolerated, with variable alteration in sensory function and minimal chance of complete sensory loss.

Other facial neuralgias.

Premise In this article we review some lesser known cranial neuralgias that are distinct from trigeminal neuralgia, trigeminal autonomic cephalalgias, or trigeminal neuropathies. Included are occipital neuralgia, superior laryngeal neuralgia, auriculotemporal neuralgia, glossopharyngeal and nervus intermedius neuralgia, and pain from acute herpes zoster and postherpetic neuralgia of the trigeminal and intermedius nerves. Problem Facial neuralgias are rare and many physicians do not see such cases in their lifetime, so patients with a suspected diagnosis within this group should be referred to a specialized center where multidisciplinary team diagnosis may be available. Potential solution Each facial neuralgia can be identified on the basis of clinical presentation, allowing for precision diagnosis and planning of treatment. Treatment remains conservative with oral or topical medication recommended for neuropathic pain to be tried before more invasive procedures are undertaken. However, evidence for efficacy of current treatments remains weak.

Functional Connectivity with the Default Mode Network Is Altered in Fibromyalgia Patients.

Fibromyalgia syndrome (FMS) patients show altered connectivity with the network maintaining ongoing resting brain activity, known as the default mode network (DMN). The connectivity patterns of DMN with the rest of the brain in FMS patients are poorly understood. This study employed seed-based functional connectivity analysis to investigate resting-state functional connectivity with DMN structures in FMS. Sixteen female FMS patients and 15 age-matched, healthy control subjects underwent T2-weighted resting-state MRI scanning and functional connectivity analyses using DMN network seed regions. FMS patients demonstrated alterations to connectivity between DMN structures and anterior midcingulate cortex, right parahippocampal gyrus, left superior parietal lobule and left inferior temporal gyrus. Correlation analysis showed that reduced functional connectivity between the DMN and the right parahippocampal gyrus was associated with longer duration of symptoms in FMS patients, whereas augmented connectivity between the anterior midcingulate and posterior cingulate cortices was associated with tenderness and depression scores. Our findings demonstrate alterations to functional connectivity between DMN regions and a variety of regions which are important for pain, cognitive and emotional processing in FMS patients, and which may contribute to the development or maintenance of chronic symptoms in FMS.

Trigeminal neuralgia: New classification and diagnostic grading for practice and research.

Trigeminal neuralgia (TN) is an exemplary condition of neuropathic facial pain. However, formally classifying TN as neuropathic pain based on the grading system of the International Association for the Study of Pain is complicated by the requirement of objective signs confirming an underlying lesion or disease of the somatosensory system. The latest version of the International Classification of Headache Disorders created similar difficulties by abandoning the term symptomatic TN for manifestations caused by major neurologic disease, such as tumors or multiple sclerosis. These diagnostic challenges hinder the triage of TN patients for therapy and clinical trials, and hamper the design of treatment guidelines. In response to these shortcomings, we have developed a classification of TN that aligns with the nosology of other neurologic disorders and neuropathic pain. We propose 3 diagnostic categories. Classical TN requires demonstration of morphologic changes in the trigeminal nerve root from vascular compression. Secondary TN is due to an identifiable underlying neurologic disease. TN of unknown etiology is labeled idiopathic. Diagnostic certainty is graded possible when pain paroxysms occur in the distribution of the trigeminal nerve branches. Triggered paroxysms permit the designation of clinically established TN and probable neuropathic pain. Imaging and neurophysiologic tests that establish the etiology of classical or secondary TN determine definite neuropathic pain.

Motor Cortex Reorganization and Repetitive Transcranial Magnetic Stimulation for Pain-A Methodological Study.

OBJECTIVES: Somatotopic reorganization of primary motor cortex (M1) has been described in several neurological conditions associated with chronic pain. We hypothesized that such reorganization impacts on the mechanisms of M1 stimulation induced analgesia and may either compromise the treatment effect of or provide an alternative target site for repetitive transcranial magnetic stimulation (rTMS). The aim of the study was to compare pain relief following rTMS of the standard motor "hotspot" with that of the reorganized area. MATERIAL AND METHODS: We used TMS motor mapping in 30 patients to establish the location of the standard motor "hotspot" (site A) and an alternative site located in the reorganized area (site B), both within M1. Where TMS mapping was not possible (N = 8) we determined the location of the two sites using task-related fMRI. We compared the analgesic effect on neuropathic pain of 5 sessions of navigated rTMS applied over (i) site A, (ii) site B, and (iii) occipital fissure (SHAM stimulation site). Total Pain Relief (TOTPAR) was determined as the difference in average weekly pain scores between baseline and following each rTMS cycle, over three weeks. RESULTS: Data from 27 patients was analyzed. rTMS of sites A and B resulted in greater TOTPAR than that of SHAM. No difference was seen between sites A and B. Responders (≥15% pain relief) were seen in both groups, with partial overlap only. Addition of stimulation over site B improved the responder rate by 58% compared with site A. In an open-label extension study of five sessions of rTMS aimed at the optimized target site, 8/11 responders and 1/12 nonresponders reported pain relief. CONCLUSIONS: Cortical reorganization may provide a more effective stimulation target for rTMS in some individuals with neuropathic pain.

Neuropathic pain: an updated grading system for research and clinical practice.

The redefinition of neuropathic pain as "pain arising as a direct consequence of a lesion or disease affecting the somatosensory system," which was suggested by the International Association for the Study of Pain (IASP) Special Interest Group on Neuropathic Pain (NeuPSIG) in 2008, has been widely accepted. In contrast, the proposed grading system of possible, probable, and definite neuropathic pain from 2008 has been used to a lesser extent. Here, we report a citation analysis of the original NeuPSIG grading paper of 2008, followed by an analysis of its use by an expert panel and recommendations for an improved grading system. As of February, 2015, 608 eligible articles in Scopus cited the paper, 414 of which cited the neuropathic pain definition. Of 220 clinical studies citing the paper, 56 had used the grading system. The percentage using the grading system increased from 5% in 2009 to 30% in 2014. Obstacles to a wider use of the grading system were identified, including (1) questions about the relative significance of confirmatory tests, (2) the role of screening tools, and (3) uncertainties about what is considered a neuroanatomically plausible pain distribution. Here, we present a revised grading system with an adjusted order, better reflecting clinical practice, improvements in the specifications, and a word of caution that even the "definite" level of neuropathic pain does not always indicate causality. In addition, we add a table illustrating the area of pain and sensory abnormalities in common neuropathic pain conditions and propose areas for further research.

Brain Areas Involved in Anticipation of Clinically Relevant Pain in Low Back Pain Populations With High Levels of Pain Behavior.

UNLABELLED: The purpose of this study was to identify neural correlates of pain anticipation in people with nonspecific low back pain (NSLBP) that correlated with pain-related distress and disability, thus providing evidence for mechanisms underlying pain behavior in this population. Thirty NSLBP sufferers, with either high levels of pain behavior or low levels on the basis of Waddell signs, were scanned with functional magnetic resonance imaging while a straight-leg raise (of the side deemed to cause moderate pain in the lower back) was performed. On each trial colored stimuli were presented and used to indicate when the leg definitely would be raised (green; 100% certainty), might be raised (yellow; 50% certainty), or would definitely not be raised (red; 100% certainty). In response to expected versus unexpected pain the group difference in activation between patients with high levels of pain behavior and low levels of pain behavior covaried as a function of anxiety scores in the right insula and pregenual anterior cingulate cortex and as a function of catastrophizing in prefrontal and parietal cortex and hippocampus. The results suggest NSLBP populations with the highest levels of pain-related distress are more likely to attend to and infer threat from innocuous cues, which may contribute to the maintenance of pain behavior associated with some chronic pain states. PERSPECTIVE: This article shows a likely neural network for exacerbating pain anticipation in NSLBP contributing to high levels of pain behavior in some people. This information could potentially help clinicians and patients to understand how anticipation of pain may contribute to patient pain and disability.