6. Persistent spinal pain syndrome type 2.

INTRODUCTION: Persistent Spinal Pain Syndrome (PSPS) refers to chronic axial pain and/or extremity pain. Two subtypes have been defined: PSPS-type 1 is chronic pain without previous spinal surgery and PSPS-type 2 is chronic pain, persisting after spine surgery, and is formerly known as Failed Back Surgery Syndrome (FBSS) or post-laminectomy syndrome. The etiology of PSPS-type 2 can be gleaned using elements from the patient history, physical examination, and additional medical imaging. Origins of persistent pain following spinal surgery may be categorized into an inappropriate procedure (eg a lumbar fusion at an incorrect level or for sacroiliac joint [SIJ] pain); technical failure (eg operation at non-affected levels, retained disk fragment, pseudoarthrosis), biomechanical sequelae of surgery (eg adjacent segment disease or SIJ pain after a fusion to the sacrum, muscle wasting, spinal instability); and complications (eg battered root syndrome, excessive epidural fibrosis, and arachnoiditis), or undetermined. METHODS: The literature on the diagnosis and treatment of PSPS-type 2 was retrieved and summarized. RESULTS: There is low-quality evidence for the efficacy of conservative treatments including exercise, rehabilitation, manipulation, and behavioral therapy, and very limited evidence for the pharmacological treatment of PSPS-type 2. Interventional treatments such as pulsed radiofrequency (PRF) of the dorsal root ganglia, epidural adhesiolysis, and spinal endoscopy (epiduroscopy) might be beneficial in patients with PSPS-type 2. Spinal cord stimulation (SCS) has been shown to be an effective treatment for chronic, intractable neuropathic limb pain, and possibly well-selected candidates with axial pain. CONCLUSIONS: The diagnosis of PSPS-type 2 is based on patient history, clinical examination, and medical imaging. Low-quality evidence exists for conservative interventions. Pulsed radiofrequency, adhesiolysis and SCS have a higher level of evidence with a high safety margin and should be considered as interventional treatment options when conservative treatment fails.

Comparative-Effectiveness study evaluating outcomes for transforaminal epidural steroid injections performed with 3% hypertonic saline or normal saline in lumbosacral radicular pain.

BACKGROUND: Transforaminal epidural steroid injection (TFESI) are commonly employed to treat lumbosacral radiculopathy. Despite anti-inflammatory properties, the addition of 3% hypertonic saline has not been studied. OBJECTIVE: Compare the effectiveness of adding 0.9% NaCl (N-group) vs. 3% NaCl (H-group) in TFESI performed for lumbosacral radiculopathy. METHODS: This retrospective study compared TFESI performed with lidocaine, triamcinolone and 0.9% NaCl. The primary outcome was the proportion of patients who experienced a ≥ 30% reduction in pain on a verbal rating scale (VRS; 0-100) at 3 months. Secondary outcome measures included the proportion of patients who improved by at least 30% for pain at 1- and 6-months, and who experienced ≥15% from baseline on the Oswestry disability index (ODI) at follow-up. RESULTS: The H-group experienced more successful pain outcomes than the N-group at 3 months (59.09% vs. 41.51%; P = 0.002) but not at 1 month (67.53% vs. 64.78%; P = 0.61) or 6 months (27.13% vs 21.55%: P = 0.31). For functional outcome, there was a higher proportion of responders in the H-group than N-group at 3 months (70.31% vs. 53.46%; P = 0.002). Female, age ≤ 60 years and duration of pain ≤ 6 months were associated with superior outcomes at the 3-month endpoint. Although those with a herniated disc experienced better outcomes in general with TFESI, the only difference favoring the H-group was for spondylolisthesis patients. CONCLUSIONS: 3% hypertonic saline is a viable alternative to normal saline as an adjunct for TFESI, with randomized studies needed to compare its effectiveness to steroids as a possible alternative. REGISTRATION: Thai Clinical Trials Registry ID TCTR 20231110006.

Smallest Clinically Meaningful Improvement in Amputation-Related Pain and Brief Pain Inventory Scores as Defined by Patient Reports of Global Improvement After Cryoneurolysis: a Retrospective Analysis of a Randomized, Controlled Clinical Trial.

BACKGROUND: The smallest meaningful improvement in pain scores (minimal clinically important difference [MCID]) after an analgesic intervention is essential information when both interpreting published data and designing a clinical trial. However, limited information is available for patients with chronic pain conditions, and what is published is derived from studies involving pharmacologic and psychological interventions. We here calculate these values based on data collected from 144 participants of a previously published multicenter clinical trial investigating the effects of a single treatment with percutaneous cryoneurolysis. METHODS: In the original trial, we enrolled patients with a lower-limb amputation and established phantom pain. Each received a single-injection femoral and sciatic nerve block with lidocaine and was subsequently randomized to receive either ultrasound-guided percutaneous cryoneurolysis or sham treatment at these same locations. Investigators, participants, and clinical staff were masked to treatment group assignment with the exception of the treating physician performing the cryoneurolysis, who had no subsequent participant interaction. At both baseline and 4 months (primary end point), participants rated their phantom limb pain based on a numeric rating scale (NRS) and their interference of pain on physical and emotional functioning as measured with the Brief Pain Inventory's interference subscale. They subsequently qualitatively defined the change using the 7-point ordinal Patient Global Impression of Change (PGIC). The smallest clinically meaningful improvements in phantom limb pain and Brief Pain Inventory scores were calculated using an anchor-based method based on the PGIC. RESULTS: The median (interquartile range [IQR]) phantom pain NRS (0-10) improvements at 4 months considered small, medium, and large were 1 [1-1], 3 [3-4], and 4 [3-6], respectively. The median improvements in the Brief Pain Inventory interference subscale (0-70) associated with a small, medium, and large analgesic changes were 16 [6-18], 24 [22-31], and 34 [22-46]. The proportions of patients that experienced PGIC ≥5 were 33% and 36% in the active and placebo groups, respectively. The relative risk of a patient experiencing PGIC ≥5 in the active group compared to the sham group with 95% confidence interval was 0.9 (0.6-1.4), P = .667. CONCLUSIONS: Amputees with phantom limb pain treated with percutaneous cryoneurolysis rate analgesic improvements as clinically meaningful similar to pharmacologic treatments, although their MCID for the Brief Pain Inventory was somewhat larger than previously published values. This information on patient-defined clinically meaningful improvements will facilitate interpretation of available studies and guide future trial design.

Pain in the Context of Sensory Deafferentation.

Pain that accompanies deafferentation is one of the most mysterious and misunderstood medical conditions. Prevalence rates for the assorted conditions vary considerably but the most reliable estimates are greater than 50% for strokes involving the somatosensory system, brachial plexus avulsions, spinal cord injury, and limb amputation, with controversy surrounding the mechanistic contributions of deafferentation to ensuing neuropathic pain syndromes. Deafferentation pain has also been described for loss of other body parts (e.g., eyes and breasts) and may contribute to between 10% and upwards of 30% of neuropathic symptoms in peripheral neuropathies. There is no pathognomonic test or sign to identify deafferentation pain, and part of the controversy surrounding it stems from the prodigious challenges in differentiating cause and effect. For example, it is unknown whether cortical reorganization causes pain or is a byproduct of pathoanatomical changes accompanying injury, including pain. Similarly, ascertaining whether deafferentation contributes to neuropathic pain, or whether concomitant injury to nerve fibers transmitting pain and touch sensation leads to a deafferentation-like phenotype can be clinically difficult, although a detailed neurologic examination, functional imaging, and psychophysical tests may provide clues. Due in part to the concurrent morbidities, the physical, psychologic, and by extension socioeconomic costs of disorders associated with deafferentation are higher than for other chronic pain conditions. Treatment is symptom-based, with evidence supporting first-line antineuropathic medications such as gabapentinoids and antidepressants. Studies examining noninvasive neuromodulation and virtual reality have yielded mixed results.

Multicenter, Randomized, Placebo-controlled Crossover Trial Evaluating Topical Lidocaine for Mechanical Cervical Pain.

BACKGROUND: There are few efficacious treatments for mechanical neck pain, with controlled trials suggesting efficacy for muscle relaxants and topical nonsteroidal anti-inflammatory drugs. Although studies evaluating topical lidocaine for back pain have been disappointing, the more superficial location of the cervical musculature suggests a possible role for topical local anesthetics. METHODS: This study was a randomized, double-blind, placebo-controlled crossover trial performed at four U.S. military, Veterans Administration, academic, and private practice sites, in which 76 patients were randomized to receive either placebo followed by lidocaine patch for 4-week intervals (group 1) or a lidocaine-then-placebo patch sequence. The primary outcome measure was mean reduction in average neck pain, with a positive categorical outcome designated as a reduction of at least 2 points in average neck pain coupled with at least a 5-point score of 7 points on the Patient Global Impression of Change scale at the 4-week endpoint. RESULTS: For the primary outcome, the median reduction in average neck pain score was -1.0 (interquartile range, -2.0, 0.0) for the lidocaine phase versus -0.5 (interquartile range, -2.0, 0.0) for placebo treatment (P = 0.17). During lidocaine treatment, 27.7% of patients experienced a positive outcome versus 14.9% during the placebo phase (P = 0.073). There were no significant differences between treatments for secondary outcomes, although a carryover effect on pain pressure threshold was observed for the lidocaine phase (P = 0.015). A total of 27.5% of patients in the lidocaine group and 20.5% in the placebo group experienced minor reactions, the most common of which was pruritis (P = 0.36). CONCLUSIONS: The differences favoring lidocaine were small and nonsignificant, but the trend toward superiority of lidocaine suggests more aggressive phenotyping and applying formulations with greater penetrance may provide clinically meaningful benefit.

Cooled radiofrequency ablation versus standard medical management for chronic sacroiliac joint pain: a multicenter, randomized comparative effectiveness study.

INTRODUCTION: Low back pain is the leading cause of disability worldwide, with sacroiliac joint pain comprising up to 30% of cases of axial lower back pain. Conservative therapies provide only modest relief. Although placebo-controlled trials show efficacy for sacral lateral branch cooled radiofrequency ablation, there are no comparative effectiveness studies. METHODS: In this randomized, multicenter comparative effectiveness study, 210 patients with clinically suspected sacroiliac joint pain who obtained short-term benefit from diagnostic sacroiliac joint injections and prognostic lateral branch blocks were randomly assigned to receive cooled radiofrequency ablation of the L5 dorsal ramus and S1-S3 lateral branches or standard medical management consisting of pharmacotherapy, injections and integrative therapies. The primary outcome measure was mean reduction in low back pain score on a 0-10 Numeric Rating Scale at 3 months. Secondary outcomes included measures of quality of life and function. RESULTS: 3 months post-treatment, the mean Numeric Rating Scale pain score for the cooled radiofrequency ablation group was 3.8±2.4 (mean reduction 2.5±2.5) compared with 5.9±1.7 (mean reduction 0.4±1.7) in the standard medical management group (p<0.0001). 52.3% of subjects in the cooled radiofrequency ablation group experienced >2 points or 30% pain relief and were deemed responders versus 4.3% of standard medical management patients (p<0.0001). Comparable improvements favoring cooled radiofrequency ablation were noted in Oswestry Disability Index score (mean 29.7±15.2 vs 41.5+13.6; p<0.0001) and quality of life (mean EuroQoL-5 score 0.68±0.22 vs 0.47±0.29; p<0.0001). CONCLUSIONS: In patients with sacroiliac joint pain, cooled radiofrequency ablation provided statistically superior improvements across the spectrum of patient outcomes compared with standard medical management. TRIAL REGISTRATION NUMBER: NCT03601949.

3. Pain originating from the lumbar facet joints.

INTRODUCTION: Pain originating from the lumbar facets can be defined as pain that arises from the innervated structures comprising the joint: the subchondral bone, synovium, synovial folds, and joint capsule. Reported prevalence rates range from 4.8% to over 50% among patients with mechanical low back pain, with diagnosis heavily dependent on the criteria employed. In well-designed studies, the prevalence is generally between 10% and 20%, increasing with age. METHODS: The literature on the diagnosis and treatment of lumbar facet joint pain was retrieved and summarized. RESULTS: There are no pathognomic signs or symptoms of pain originating from the lumbar facet joints. The most common reported symptom is uni- or bilateral (in more advanced cases) axial low back pain, which often radiates into the upper legs in a non-dermatomal distribution. Most patients report an aching type of pain exacerbated by activity, sometimes with morning stiffness. The diagnostic value of abnormal radiologic findings is poor owing to the low specificity. SPECT can accurately identify joint inflammation and has a predictive value for diagnostic lumbar facet injections. After "red flags" are ruled out, conservatives should be considered. In those unresponsive to conservative therapy with symptoms and physical examination suggesting lumbar facet joint pain, a diagnostic/prognostic medial branch block can be performed which remains the most reliable way to select patients for radiofrequency ablation. CONCLUSIONS: Well-selected individuals with chronic low back originating from the facet joints may benefit from lumbar medial branch radiofrequency ablation.

1. Lumbosacral radicular pain.

INTRODUCTION: Patients suffering lumbosacral radicular pain report radiating pain in one or more lumbar or sacral dermatomes. In the general population, low back pain with leg pain extending below the knee has an annual prevalence that varies from 9.9% to 25%. METHODS: The literature on the diagnosis and treatment of lumbosacral radicular pain was reviewed and summarized. RESULTS: Although a patient's history, the pain distribution pattern, and clinical examination may yield a presumptive diagnosis of lumbosacral radicular pain, additional clinical tests may be required. Medical imaging studies can demonstrate or exclude specific underlying pathologies and identify nerve root irritation, while selective diagnostic nerve root blocks can be used to confirm the affected level(s). In subacute lumbosacral radicular pain, transforaminal corticosteroid administration provides short-term pain relief and improves mobility. In chronic lumbosacral radicular pain, pulsed radiofrequency (PRF) treatment adjacent to the spinal ganglion (DRG) can provide pain relief for a longer period in well-selected patients. In cases of refractory pain, epidural adhesiolysis and spinal cord stimulation can be considered in experienced centers. CONCLUSIONS: The diagnosis of lumbosacral radicular pain is based on a combination of history, clinical examination, and additional investigations. Epidural steroids can be considered for subacute lumbosacral radicular pain. In chronic lumbosacral radicular pain, PRF adjacent to the DRG is recommended. SCS and epidural adhesiolysis can be considered for cases of refractory pain in specialized centers.

4. Painful diabetic polyneuropathy.

INTRODUCTION: Pain as a symptom of diabetic polyneuropathy (DPN) significantly lowers quality of life, increases mortality and is the main reason for patients with diabetes to seek medical attention. The number of people suffering from painful diabetic polyneuropathy (PDPN) has increased significantly over the past decades. METHODS: The literature on the diagnosis and treatment of diabetic polyneuropathy was retrieved and summarized. RESULTS: The etiology of PDPN is complex, with primary damage to peripheral nociceptors and altered spinal and supra-spinal modulation. To achieve better patient outcomes, the mode of diagnosis and treatment of PDPN evolves toward more precise pain-phenotyping and genotyping based on patient-specific characteristics, new diagnostic tools, and prior response to pharmacological treatments. According to the Toronto Diabetic Neuropathy Expert Group, a presumptive diagnosis of "probable PDPN" is sufficient to initiate treatment. Proper control of plasma glucose levels, and prevention of risk factors are essential in the treatment of PDPN. Mechanism-based pharmacological treatment should be initiated as early as possible. If symptomatic pharmacologic treatment fails, spinal cord stimulation (SCS) should be considered. In isolated cases, where symptomatic pharmacologic treatment and SCS are unsuccessful or cannot be used, sympathetic lumbar chain neurolysis and/or radiofrequency ablation (SLCN/SLCRF), dorsal root ganglion stimulation (DRGs) or posterior tibial nerve stimulation (PTNS) may be considered. However, it is recommended that these treatments be applied only in a study setting in a center of expertise. CONCLUSIONS: The diagnosis of PDPN evolves toward pheno-and genotyping and treatment should be mechanism-based.

5. Sacroiliac joint pain.

INTRODUCTION: Sacroiliac (SI) joint pain is defined as pain localized in the anatomical region of the SI joint. The reported prevalence of SI joint pain among patients with mechanical low back pain varies between 15% and 30%. METHODS: In this narrative review, the literature on the diagnosis and treatment of SI joint pain was updated and summarized. RESULTS: Patient's history provides clues on the source of pain. The specificity and sensitivity of provocative maneuvers are relatively high when three or more tests are positive, though recent studies have questioned the predictive value of single or even batteries of provocative tests. Medical imaging is indicated only to rule out red flags for potentially serious conditions. The diagnostic value of SI joint infiltration with local anesthetic remains controversial due to the potential for false-positive and false-negative results. Treatment of SI joint pain ideally consists of a multidisciplinary approach that includes conservative measures as first-line therapies (eg, pharmacological treatment, cognitive-behavioral therapy, manual medicine, exercise therapy and rehabilitation treatment, and if necessary, psychological support). Intra- and extra-articular corticosteroid injections have been documented to produce pain relief for over 3 months in some people. Radiofrequency ablation (RFA) of the L5 dorsal ramus and S1-3 (or 4) lateral branches has been shown to be efficacious in numerous studies, with extensive lesioning strategies (eg, cooled RFA) demonstrating the strongest evidence. The reported rate of complications for SI joint treatments is low. CONCLUSIONS: SI joint pain should ideally be managed in a multidisciplinary and multimodal manner. When conservative treatment fails, corticosteroid injections and radiofrequency treatment can be considered.

The potential of a multimodal digital care program in addressing healthcare inequities in musculoskeletal pain management.

Digital interventions have emerged as a solution for time and geographical barriers, however, their potential to target other social determinants of health is largely unexplored. In this post-hoc analysis, we report the impact of social deprivation on engagement and clinical outcomes after a completely remote multimodal musculoskeletal (MSK) digital care program managed by a culturally-sensitive clinical team. Patients were stratified in five categories according to their social deprivation index, and cross-referenced with their race/ethnicity, rurality and distance to healthcare facilities. From a total of 12,062 patients from all U.S. states, 8569 completed the program. Higher social deprivation was associated with greater baseline disease burden. We observed that all categories reported pain improvements (ranging from -2.0 95%CI -2.1, -1.9 to -2.1 95%CI -2.3, -1.9, p < 0.001) without intergroup differences in mean changes or responder rates (from 59.9% (420/701) to 66.6% (780/1172), p = 0.067), alongside reduction in analgesic consumption. We observed significant improvements in mental health and productivity across all categories, with productivity and non-work-related functional recovery being greater within the most deprived group. Engagement was high but varied slightly across categories. Together these findings highlight the importance of a patient-centered digital care program as a tool to address health inequities in musculoskeletal pain management. The idea of investigating social deprivation within a digital program provides a foundation for future work in this field to identify areas of improvement.

Cost-Effectiveness and Cost-Utility Analyses in Thailand of Continuous Intrathecal Morphine Infusion Compared with Conventional Therapy in Cancer Pain: A 10-year Multicenter Retrospective Study.

Background: Because of the high initial cost of intrathecal drug delivery (ITDD) therapy, this study investigated the cost-effectiveness and cost-utility of ITDD therapy in refractory cancer pain management in Thailand over the past 10 years. Methods: The retrospective study was conducted in patients with cancer pain who underwent ITDD therapy from January 2011 to 2021 at three university hospitals. Clinical outcomes included the numerical rating scale (NRS), Palliative Performance Scale, and the EQ-5D. The direct medical and nonmedical as well as indirect costs were also recorded. Cost-effectiveness and cost-utility analyses were performed comparing ITDD therapy with conventional therapy (extrapolated from costs of the same patient before ITDD therapy) from a societally oriented economic evaluation. Results: Twenty patients (F:M: 10:10) aged 60 ± 15 years who underwent implantation of an intrathecal percutaneous port (IT port; n = 15) or programmable intrathecal pump (IT pump; n = 5) were included. The median survival time was 78 (interquartile range = 121-54) days after ITDD therapy. At 2-month follow-up, the incremental cost-effectiveness ratio (ICER)/pain reduction of an IT port (US$2065.36 (CA$2829.54)/2-point NRS reduction/lifetime) was lower than for patients with an IT pump (US$5479.26 (CA$7506.58)/2-point NRS reduction/lifetime) compared with continued conventional therapy. The ICER/quality-adjusted life years (QALYs) gained for an IT port compared with conventional treatment was US$93,999.31(CA$128,799.06)/QALY gained, which is above the cost-effectiveness threshold for Thailand. Conclusion: The cost-effectiveness and cost-utility of IT port therapy for cancer pain was high relative to the cost of living in Thailand, above the cost-effectiveness threshold. Prospective cost analysis studies enrolling more patients with diverse cancers that investigate the benefit of early ITDD therapy with devices over a range of prices are warranted.

Contexte: En raison du coût initial élevé du traitement par administration intrathécale de médicaments (AIM), cette étude a étudié le rapport coût-efficacité et le rapport coût-utilité du traitement par AIM dans la prise en charge de la douleur cancéreuse réfractaire en Thaïlande au cours des 10 dernières années.Méthodes: L'étude rétrospective a été menée auprès de patients souffrant de douleur cancéreuse ayant subi un traitement par AIM de janvier 2011 et 2021 dans trois hôpitaux universitaires. Les résultats cliniques comprenaient l'échelle d'évaluation numérique (EEN), l'échelle de performance palliative et l'EQ-5D. Les coûts médicaux et non médicaux directs et indirects ont également été consignés. Les analyses coûts-efficacité et coût-utilité ont été effectuées en comparant le traitement par AIM au traitement conventionnel (extrapolé à partir des coûts pour le même patient avant le traitement par AIM) à partir d'une évaluation économique sociétale.Résultats: Vingt patients (F : M : 10 : 10) âgés de 60 ± 15 ans ayant subi l'implantation d'un port percutané intrathécal (port IT; n = 15) ou d'une pompe intrathécale programmable (pompe IT; n = 5) ont été inclus. Le temps de survie médian était de 78 jours (intervalle interquartile = 121­54) après le traitement par AIM. À deux mois de suivi, le ratio coût-efficacité incrémental (RCEI/réduction de la douleur d'un port IT (2 065,36 $ US (2 829,54 $ CA) /réduction de 2 points sur l'EEN/durée de vie) était inférieur à celui des patients avec une pompe IT (5479,26 $ US (7506,58 $ CA) /réduction de 2 points sur l'EEN/durée de vie) comparativement au traitement conventionnel en continu. Le RCEI/année de vie pondérée par la qualité (AVPQ) gagnée pour un port IT comparativement au traitement conventionnel était de 93 999,31 $ US (128 799,06 $ CA) /AVPQ gagné, ce qui est au-dessus du seuil de rentabilité pour la Thaïlande.Conclusion: Le rapport coût-efficacité et le rapport coût-utilité du traitement par port IT pour la douleur cancéreuse étaient élevés par rapport au coût de la vie en Thaïlande, soit au-dessus du seuil de rentabilité. Les études d'analyse de coût prospectives portant sur un plus grand nombre de patients atteints de divers cancers qui étudient les avantages des traitements par AIM précoces à l'aide d'appareils de prix différents sont justifiées.

Ketamine Infusions for Treatment-Resistant Neuropathic Pruritus.

This case report describes a patient in her 50s with a 4-year history of brachioradial pruritus with bilateral pruritus on her upper arms and forearms.

Antimicrobial therapies for chronic pain (part 1): analgesic mechanisms.

There is increasing evidence that the relationship between chronic pain and infections is complex and intertwined. Bacterial and viral infections can cause pain through numerous mechanisms such as direct tissue damage and inflammation, the induction of excessive immunologic activity, and the development of peripheral or central sensitization. Treating infections might relieve pain by attenuating these processes, but a growing body of literature suggests that some antimicrobial therapies confer analgesic effects, including for nociceptive and neuropathic pain symptoms, and affective components of pain. The analgesic mechanisms of antimicrobials are indirect, but might be conceptualized into two broad categories: 1) the reduction of the infectious burden and associated pro-inflammatory processes; and 2) the inhibition of signaling processes (e.g., enzymatic and cytokine activity) necessary for nociception and maladaptive neuroplastic changes via off-target effects (unintended binding sites). For the former, there is evidence that symptoms of chronic low back pain (when associated with Modic type 1 changes), irritable bowel syndrome, inflammatory bowel disease, chronic pelvic pain, and functional dyspepsia might be improved after antibiotic treatment, though significant questions remain regarding specific regimens and dose, and which subpopulations are most likely to benefit. For the latter, there is evidence that several antimicrobial classes and medications exert analgesic effects independent of their reduction of infectious burden, and these include cephalosporins, ribavirin, chloroquine derivatives, rapalogues, minocycline, dapsone, and piscidin-1. This article aims to comprehensively review the existing literature for antimicrobial agents that have demonstrated analgesic efficacy in preclinical or clinical studies.