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.

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 injections (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 vs. lidocaine, triamcinolone and 3% 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 = .002) but not at 1 month (67.53% vs. 64.78%; P = .61) or 6 months (27.13% vs 21.55%: P = .31). For functional outcome, there was a higher proportion of responders in the H-group than the N-group at 3 months (70.31% vs. 53.46%; P = .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.

Lumbar transforaminal epidural steroid injections with particulate vs. nonparticulate steroid: an evidence-informed review on shifting gear to a personalized medicine paradigm.

PURPOSE OF REVIEW: To provide an evidence-informed review weighing the pros and cons of particulate vs. nonparticulate steroids for lumbar transforaminal epidural steroid injections (TFESI). RECENT FINDINGS: The relative use of nonparticulate vs. particulate steroids for lumbar TFESI has risen recently in light of catastrophic consequences reported for the latter during cervical TFESI. Among various causes of spinal cord infarct, an exceedingly rare event in the lower lumbar spine, embolization of particulate steroid is among the least likely. Case reports have documented cases of spinal cord infarct during lower lumbar TFESI with both particulate and nonparticulate steroids, with database reviews finding no difference in complication rates. There is some evidence for superiority of particulate over nonparticulate steroids in well-designed studies, which could lead to increase steroid exposure (i.e. more injections) and treatment failure resulting in surgical and/or opioid management when nonparticulate steroids are utilized. SUMMARY: Similar to a paradigm shift in medicine, a personalized approach based on a shared decision model and the consequences of treatment failure, should be utilized in deciding which steroid to utilize. Alternatives to ESI include high-volume injections with nonsteroid solutions, and the use of hypertonic saline, which possesses anti-inflammatory properties and has been shown to be superior to isotonic saline in preliminary clinical studies.

12. vascular pain Ischemic pain in the extremities and Raynaud's syndrome.

INTRODUCTION: Peripheral artery diseases (PAD) and Raynaud's syndrome are associated with substantial morbidity. PAD, through the restriction of blood flow to the extremities, may lead to critical limb ischemia with symptoms of pain at rest which may eventually progress to severe limb ischemia with gangrene. This serious and painful clinical condition requires extensive medical care, is limb-threatening and, in case of delayed or unsuccessful treatment, is associated with a high mortality rate. In Raynaud's syndrome, the blood supply to certain parts of the body, usually the fingers and toes and less frequently the nose or ears, is restricted because of vasculopathy of the smaller vessels at acral sites. Under certain circumstances, with cold as the most well-known provoking factor, blood flow restriction occurs, leading to demarcated color changes and symptoms such as pain, paresthesia, and numbness. In severe cases of Raynaud syndrome tissue ischemia may lead to necrosis and the need for amputation of the affected area. METHODS: In this narrative review, the literature on the diagnosis and interventional pain treatment of PAD and Raynaud's syndrome was updated and summarized. OBJECTIVES: This review focused on interventional pain treatment. In PAD, the effects of the intervention on limb salvage, ulcer healing, and ischemic pain were summarized. Additionally, results with respect to skin microcirculation and quality of life were reported if available. In Raynaud's syndrome, we focused on the effect of the intervention on peripheral blood flow metrics and pain intensity during attacks. RESULTS: In PAD, prevention and treatment of risk factors are important. Initially, conservative treatment and pharmacological therapy are preferred first-line therapies. However, when disease progression occurs, interventional management may be considered. The literature search yielded conflicting evidence for sympathectomy as a treatment for PAD. Spinal cord stimulation (SCS) as a treatment modality for advanced PAD had high-quality evidence for limb salvage in subgroups of patients but conflicting evidence for other outcome measures such as pain, wound healing, and quality of life. The literature search for interventional pain management in Raynaud's syndrome was limited to only one randomized controlled trial (RCT) studying the effect of thoracic sympathectomy. This study had several limitations and hence the level of evidence for this interventional treatment is very low. No RCTs studying SCS in patients with Raynaud's syndrome were found. CONCLUSIONS: In both PAD and Raynaud's syndrome, additional RCTs are needed to substantiate interventional (pain) management and bolster the evidence base for sympathectomy and SCS as treatment options.

11. Cervicogenic headache and occipital neuralgia.

INTRODUCTION: Cervicogenic headache (CEH) and occipital neuralgia (ON) are headaches originating in the occiput and that radiate to the vertex. Because of the intimate relationship between structures based in the occiput and those in the upper cervical region, there is significant overlap between the presentation of CEH and ON. Diagnosis starts with a headache history to assess for diagnostic criteria formulated by the International Headache Society. Physical examination evaluates range of motion of the neck and the presence of tender areas or pressure points. METHODS: The literature for the diagnosis and treatment of CEH and ON was searched from 2015 through August 2022, retrieved, and summarized. RESULTS: Conservative treatment includes pain education and self-care, analgesic medication, physical therapy (such as reducing secondary muscle tension and improving posture), the use of TENS (transcutaneous electrical nerve stimulation), or a combination of the aforementioned treatments. Injection at various anatomical locations with local anesthetic with or without corticosteroids can provide pain relief for a short period. Deep cervical plexus block can result in improved pain for less than 6 months. In both CEH and ON, an occipital nerve block can provide important diagnostic information and improve pain in some patients, with PRF providing greater long-term pain control. Radiofrequency ablation of the cervical facet joints can result in improvement for over 1 year. Occipital nerve stimulation (ONS) should be considered for the treatment of refractory ON. CONCLUSION: The treatment of CEH preferentially consists of radiofrequency treatment of the facet joints, while for ON, pulsed radiofrequency of the occipital nerves is indicated. For refractory cases, ONS may be considered.

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.

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.

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.

10. Complex regional pain syndrome.

INTRODUCTION: Complex regional pain syndrome (CRPS) is a clinical disorder that can develop following surgery or trauma. Based on the most prominent underlying pathophysiological mechanisms, CRPS can be classified into different subtypes, namely inflammatory, nociplastic/neuropathic, vasomotor, and motor. Depending on the subtype, personalized treatment can be applied. If conservative treatments are insufficient or ineffective, more invasive treatments may be recommended. This article provides an overview of the most recent insights into CRPS and discusses the most common invasive treatments. METHODS: The literature regarding interventional treatments for CRPS has been systematically reviewed and summarized. RESULTS: Bisphosphonates are effective in treating the inflammatory subtype, while ketamine can provide pain relief for the nociplastic/neuropathic subtype. Sympathetic blocks are effective in addressing vasomotor disturbances. For patients with refractory symptoms, neurostimulation is a viable option due to its multimechanistic properties for all subtypes. End-of-line motor disturbances may benefit from intrathecal baclofen. CONCLUSIONS: CRPS is a debilitating condition with an unpredictable course. The effectiveness of treatment varies from patient to patient. When conservative approaches prove insufficient, gradual progression to invasive treatments based on the underlying subtype is recommended.

8. Herpes zoster and post herpetic neuralgia.

INTRODUCTION: Patients suffering from postherpetic neuralgia (PHN) report unilateral chronic pain in one or more dermatomes after an acute herpes zoster (HZ) infection. The incidence of acute HZ ranges between three and five patients per 1000 person-years. In one out of four patients, acute HZ-related pain will transition into PHN. PHN can be very disabling for patients and reduce quality of life. Additionally, the treatment of PHN is characterized by high failure rates. The aim of this review is to give an update on the previous practical guideline published in 2011 and revised in 2015 (published in 2019) and to provide an overview of current interventional treatment options for HZ infection and PHN. METHODS: The literature on the diagnosis and treatment of HZ and PHN was systematically reviewed and summarized. RESULTS: The most important treatment for acute HZ-related pain is antiviral therapy within 72 h of symptom onset. Additional symptomatic treatment options are analgesic drugs according to the WHO pain ladder, tricyclic antidepressants (eg, nortriptyline), and antiepileptic drugs (eg, gabapentin). If pain is not sufficiently reduced, interventional treatment such as an epidural injection with local anesthetics and corticosteroids or pulsed radiofrequency of the dorsal root ganglion (DRG) are options. Treatment for PHN is preferably transdermal capsaicin, lidocaine, or oral drugs such as antidepressants or antiepileptics. CONCLUSIONS: Treatment of acute HZ-related pain especially PHN is challenging. Besides the conventional treatment for PHN, interventional management is considered a new treatment option. PRF of DRG seems to be the most promising interventional management.

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.

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.

9. Chronic knee pain.

INTRODUCTION: Chronic knee pain is defined as pain that persists or recurs over 3 months. The most common is degenerative osteoarthritis (OA). This review represents a comprehensive description of the pathology, diagnosis, and treatment of OA of the knee. METHODS: The literature on the diagnosis and treatment of chronic knee pain was retrieved and summarized. A modified Delphi approach was used to formulate recommendations on interventional treatments. RESULTS: Patients with knee OA commonly present with insidious, chronic knee pain that gradually worsens. Pain caused by knee OA is predominantly nociceptive pain, with occasional nociplastic and infrequent neuropathic characteristics occurring in a diseased knee. A standard musculoskeletal and neurological examination is required for the diagnosis of knee OA. Although typical clinical OA findings are sufficient for diagnosis, medical imaging may be performed to improve specificity. The differential diagnosis should exclude other causes of knee pain including bone and joint disorders such as rheumatoid arthritis, spondylo- and other arthropathies, and infections. When conservative treatment fails, intra-articular injections of corticosteroids and radiofrequency (conventional and cooled) of the genicular nerves have been shown to be effective. Hyaluronic acid infiltrations are conditionally recommended. Platelet-rich plasma infiltrations, chemical ablation of genicular nerves, and neurostimulation have, at the moment, not enough evidence and can be considered in a study setting. The decision to perform joint-preserving and joint-replacement options should be made multidisciplinary. CONCLUSIONS: When conservative measures fail to provide satisfactory pain relief, a multidisciplinary approach is recommended including psychological therapy, integrative treatments, and procedural options such as intra-articular injections, radiofrequency ablation, and surgery.

Ultrasound-guided Percutaneous Cryoneurolysis to Treat Chronic Postamputation Phantom Limb Pain: A Multicenter Randomized Controlled Trial.

BACKGROUND: Postamputation phantom pain is notoriously persistent with few validated treatments. Cryoneurolysis involves the application of low temperatures to reversibly ablate peripheral nerves. The authors tested the hypothesis that a single cryoneurolysis treatment would decrease phantom pain 4 months later. METHODS: The authors 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. The primary outcome was the change in average phantom pain intensity between baseline and 4 months as measured with a numeric rating scale (0 to 10), after which an optional crossover treatment was offered. 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. RESULTS: Pretreatment phantom pain scores were similar in both groups, with a median [quartiles] of 5.0 [4.0, 6.0] for active treatment and 5.0 [4.0, 7.0] for sham. After 4 months, pain intensity decreased by 0.5 [-0.5, 3.0] in patients given cryoneurolysis (n = 71) versus 0 [0, 3] in patients given sham (n = 73), with an estimated difference (95% CI) of -0.1 (-1.0 to 0.7), P = 0.759. Following their statistical gatekeeping protocol, the authors did not make inferences or draw conclusions on secondary endpoints. One serious adverse event occurred after a protocol deviation in which a femoral nerve cryolesion was induced just below the inguinal ligament-instead of the sensory-only saphenous nerve-which resulted in quadriceps weakness, and possibly a fall and clavicle fracture. CONCLUSIONS: Percutaneous cryoneurolysis did not decrease chronic lower extremity phantom limb pain 4 months after treatment. However, these results were based upon the authors' specific study protocol, and since the optimal cryoneurolysis treatment parameters such as freeze duration and anatomic treatment location remain unknown, further research is warranted.

Fear Avoidance Beliefs in Upper-Extremity Musculoskeletal Pain Conditions: Secondary Analysis of a Prospective Clinical Study on Digital Care Programs.

BACKGROUND: Fear-avoidance beliefs (FAB) have been associated with poorer prognosis and decreased adherence to exercise-based treatments in musculoskeletal (MSK) pain. However, the impact of high FAB on adherence and outcomes in upper extremity MSK (UEMSK) pain is poorly explored, particularly through exercise-based digital care programs (DCP). OBJECTIVE: Assess the adherence levels, clinical outcomes and satisfaction in patients with UEMSK pain and elevated FAB after a fully remote multimodal DCP. Associations between FABQ-PA and clinical outcomes were conducted. METHODS: Secondary analysis of an ongoing clinical trial. Participants with UEMSK pain (shoulder, elbow, and wrist/hand) and elevated FAB-physical activity (FABQ-PA ≥ 15) were included. Adherence (completion rate, sessions/week, total exercise time) and mean change in clinical outcomes-disability (QuickDASH), numerical pain score, FABQ-PA, anxiety (GAD-7), and depression (PHQ-9)-between baseline and end-of-program were assessed. Associations between FABQ-PA and clinical outcomes were conducted. RESULTS: 520 participants were included, with mean baseline FABQ-PA of 18.02 (SD 2.77). Patients performed on average 29.3 exercise sessions (2.8 sessions/week), totalizing 338.2 exercise minutes. Mean satisfaction was 8.5/10 (SD 1.7). Significant improvements were observed in all clinical outcomes. Higher baseline FAB were associated with higher baseline disability (P < .001), and smaller improvements in disability (P < .001) and pain (P = .001). Higher engagement was associated with greater improvements in FABQ-PA (P = .043) and pain (P = 0.009). CONCLUSIONS: This study provides evidence of the potential benefits of a structured and multimodal home-based DCP in the management of UEMSK pain conditions in patients with elevated FAB in a real-world context.

Safety of Scrambler Therapy: A Systematic Review of Complications and Adverse Effects.

OBJECTIVE: The objective was to qualitatively synthesize all reported cases of complications, adverse effects, side effects, or harms arising from the use of scrambler therapy (ST). METHODS AND DESIGN: A systematic review was conducted according to the Preferred Reporting Items for Systematic Reviews and Meta-Analysis guidelines. The PubMed, Embase, Scopus, Web of Science, United States National Library of Medicine clinical trials registry, and Cochrane Central Register of Controlled Trials databases were searched from database inception to December 10, 2021. Case reports/series, abstracts, retrospective studies, and prospective studies (e.g., open-label trials, randomized controlled trials) pertaining to ST and any description of a complication, adverse effect, side effect, or harm were screened. The search protocol was developed a priori and registered via the International Prospective Register of Systematic Reviews (PROSPERO ID: CRD42021291838). RESULTS: A total of six RCTs, 19 prospective open-label trials, and 11 case series / case reports met the inclusion criteria, comprising 1,152 total patients. Two patients experienced contact dermatitis, and one patient reported minor ecchymosis that resolved without intervention. This yielded a composite complication rate of 0.26% (3/1,152). There were zero reported serious adverse events. CONCLUSIONS: When used in accordance with the treatment protocols described by the United States Food and Drug Administration and device manual, ST is associated with a reported composite complication rate that is orders of magnitude lower than those of invasive neuromodulation devices. ST neuromodulation is a safe alternative for patients who cannot undergo invasive neuromodulation device implantation because of either risk or preference.

Sympathetic Blocks as a Predictor for Response to Ketamine Infusion in Patients with Complex Regional Pain Syndrome: A Multicenter Study.

BACKGROUND: Ketamine infusions are frequently employed for refractory complex regional pain syndrome (CRPS), but there are limited data on factors associated with treatment response. Sympathetic blocks are also commonly employed in CRPS for diagnostic and therapeutic purposes and generally precede ketamine infusions. OBJECTIVES: We sought to determine whether demographic and clinical factors, and technical and psychophysical characteristics of sympathetic blocks are associated with response to ketamine infusion. METHODS: In this multi-center retrospective study, 71 patients who underwent sympathetic blocks followed by ketamine infusions at 4 hospitals were evaluated. Sympathetically maintained pain (SMP) was defined as ≥ 50% immediate pain relief after sympathetic block and a positive response to ketamine was defined as ≥ 30% pain relief lasting over 3 weeks. RESULTS: Factors associated with a positive response to ketamine in univariable analysis were the presence of SMP (61.0% success rate vs 26.7% in those with sympathetically independent pain; P = .009) and post-block temperature increase (5.66 ± 4.20 in ketamine responders vs 3.68 ± 3.85 in non-responders; P = .043). No psychiatric factor was associated with ketamine response. In multivariable analysis, SMP (OR 6.54 [95% CI 1.83, 23.44]) and obesity (OR 8.75 [95% 1.45, 52.73]) were associated with a positive ketamine infusion outcome. CONCLUSIONS: The response to sympathetic blocks may predict response to ketamine infusion in CRPS patients, with alleviation of the affective component of pain and predilection to a positive placebo effect being possible explanations.

Comparing Digital to Conventional Physical Therapy for Chronic Shoulder Pain: Randomized Controlled Trial.

BACKGROUND: Chronic shoulder pain (CSP) is a common condition with various etiologies, including rotator cuff disorders, adhesive capsulitis, shoulder instability, and shoulder arthritis. It is associated with substantial disability and psychological distress, resulting in poor productivity and quality of life. Physical therapy constitutes the mainstay treatment for CSP, but several barriers exist in accessing care. In recent years, telerehabilitation has gained momentum as a potential solution to overcome such barriers. It has shown numerous benefits, including improving access and convenience, promoting patient adherence, and reducing costs. However, to date, no previous randomized controlled trial has compared fully remote digital physical therapy to in-person rehabilitation for nonoperative CSP. OBJECTIVE: The aim of this study is to compare clinical outcomes between digital physical therapy and conventional in-person physical therapy in patients with CSP. METHODS: We conducted a single-center, parallel-group, randomized controlled trial involving 82 patients with CSP referred for outpatient physical therapy. Participants were randomized into digital or conventional physical therapy (8-week interventions). The digital intervention consisted of home exercise, education, and cognitive behavioral therapy (CBT), using a device with movement digitalization for biofeedback and asynchronous physical therapist monitoring through a cloud-based portal. The conventional group received in-person physical therapy, including exercises, manual therapy, education, and CBT. The primary outcome was the change (baseline to 8 weeks) in function and symptoms using the short-form of Disabilities of the Arm, Shoulder, and Hand questionnaire. Secondary outcome measures included self-reported pain, surgery intent, analgesic intake, mental health, engagement, and satisfaction. All questionnaires were delivered electronically. RESULTS: A total of 90 participants were randomized into digital or conventional physical therapy, with 82 receiving the allocated intervention. Both groups experienced significant improvements in function measured by the short-form of the Disabilities of the Arm, Shoulder, and Hand questionnaire, with no differences between groups (-1.8, 95% CI -13.5 to 9.8; P=.75). For secondary outcomes, no differences were observed in surgery intent, analgesic intake, and mental health or worst pain. Higher reductions were observed in average and least pain in the conventional group, which, given the small effect sizes (least pain 0.15 and average pain 0.16), are unlikely to be clinically meaningful. High adherence and satisfaction were observed in both groups, with no adverse events. CONCLUSIONS: This study shows that fully remote digital programs can be viable care delivery models for CSP given their scalability and effectiveness, assessed through comparison with high-dosage in-person rehabilitation. TRIAL REGISTRATION: ClinicalTrials.gov (NCT04636528); https://clinicaltrials.gov/study/NCT04636528.