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.

Large-scale real-world data on a multidisciplinary approach to spinal cord stimulation for persistent spinal pain syndromes: first evaluation of the Neuro-Pain® nationwide screening and follow-up interactive register.

Introduction: Spinal cord stimulation is a common treatment option for neuropathic pain conditions. Despite its extensive use and multiple technological evolutions, long term efficacy of spinal cord stimulation is debated. Most studies on spinal cord stimulation include a rather limited number of patients and/or follow-ups over a limited period. Therefore, there is an urgent need for real-world, long-term data. Methods: In 2018, the Belgian government initiated a nationwide secure platform for the follow-up of all new and existing spinal cord stimulation therapies. This is a unique approach used worldwide. Four years after the start of centralized recording, the first global extraction of data was performed. Results: Herein, we present the findings, detailing the different steps in the centralized procedure, as well as the observed patient and treatment characteristics. Furthermore, we identified dropouts during the screening process, the reasons behind discontinuation, and the evolution of key indicators during the trial period. In addition, we obtained the first insights into the evolution of the clinical impact of permanent implants on the overall functioning and quality of life of patients in the long-term. Discussion: Although these findings are the results of the first data extraction, some interesting conclusions can be drawn. The long-term outcomes of neuromodulation are complex and subject to many variables. Future data extraction will allow us to identify these confounding factors and the early predictors of success. In addition, we will propose further optimization of the current process.

Radiofrequency for chronic lumbosacral and cervical pain: Results of a consensus study using the RAND/UCLA appropriateness method.

BACKGROUND: Despite the routine use of radiofrequency (RF) for the treatment of chronic pain in the lumbosacral and cervical region, there remains uncertainty on the most appropriate patient selection criteria. This study aimed to develop appropriateness criteria for RF in relation to relevant patient characteristics, considering RF ablation (RFA) for the treatment of chronic axial pain and pulsed RF (PRF) for the treatment of chronic radicular pain. METHODS: The RAND/UCLA Appropriateness Method (RUAM) was used to explore the opinions of a multidisciplinary European panel on the appropriateness of RFA and PRF for a variety of clinical scenarios. Depending on the type of pain (axial or radicular), the expert panel rated the appropriateness of RFA and PRF for a total of 219 clinical scenarios. RESULTS: For axial pain in the lumbosacral or cervical region, appropriateness of RFA was determined by the dominant pain trigger and location of tenderness on palpation with higher appropriateness scores if these variables were suggestive of the diagnosis of facet or sacroiliac joint pain. Although the opinions on the appropriateness of PRF for lumbosacral and cervical radicular pain were fairly dispersed, there was agreement that PRF is an appropriate option for well-selected patients with radicular pain due to herniated disc or foraminal stenosis, particularly in the absence of motor deficits. The panel outcomes were embedded in an educational e-health tool that also covers the psychosocial aspects of chronic pain, providing integrated recommendations on the appropriate use of (P)RF interventions for the treatment of chronic axial and radicular pain in the lumbosacral and cervical region. CONCLUSIONS: A multidisciplinary European expert panel established patient-specific recommendations that may support the (pre)selection of patients with chronic axial and radicular pain in the lumbosacral and cervical region for either RFA or PRF (accessible via https://rftool.org). Future studies should validate these recommendations by determining their predictive value for the outcomes of (P)RF interventions.

Cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: 12-month and cost-effectiveness results from the multicenter COCOGEN trial.

BACKGROUND: Radiofrequency (RF) treatment of the genicular nerves reduces chronic knee pain in patients with osteoarthritis (OA) or persistent postsurgical pain (PPSP) after total knee arthroplasty (TKA). The objective of this study is to compare long-term outcomes of cooled and conventional RF and perform an economic evaluation. METHODS: The COCOGEN trial is a double-blinded, non-inferiority, pilot, randomized controlled trial that compared the effects up to 12 months of cooled and conventional RF in patients with chronic knee pain suffering from OA or PPSP after TKA following a 1:1 randomization rate. Outcomes were knee pain, functionality, quality of life, emotional health, medication use, and adverse events. A trial-based economic evaluation was performed with a 12-month societal perspective. Here, the primary outcome was the incremental costs per quality-adjusted life year (QALY). RESULTS: 41 of the 49 included patients completed the 12-month follow-up. One patient in the PPSP cooled RF group had substantial missing data at 12-month follow-up. The proportion of patients with ≥50% pain reduction at 12 months was 22.2% (4/18) in patients treated with conventional RF versus 22.7% (5/22) in patients treated with cooled RF (p>0.05). There was a statistically significant difference in the mean absolute numerical rating scale at 12 months after cooled RF and conventional RF in patients with PPSP (p=0.02). Differences between other outcomes were not statistically significant. The health economic analysis indicated that cooled RF resulted in lower costs and improved QALYs compared with conventional RF in PPSP but not in OA. There were no serious adverse events. CONCLUSIONS: Both RF treatments demonstrated in approximately 22% of patients a ≥50% pain reduction at 12 months. In patients with PPSP, contrary to OA, cooled RF seems to be more effective than conventional RF. Additionally, cooled RF has in patients with PPSP, as opposed to OA, greater effectiveness at lower costs compared with conventional RF. TRIAL REGISTRATION NUMBER: NCT03865849.

Expectations of treatment outcome in complex cases of patients with chronic pain: A study on the DATAPAIN cohort.

BACKGROUND: A better insight in how the biopsychosocial factors influence patient outcome(s) may provide information that helps selecting the optimal pain management for a specific group. METHODS: Categorization was made in the prospective DATAPAIN registry, in which patients with pain severity (Numeric Rating Scale [NRS]: 7-10), depression or anxiety (Hospital Anxiety and Depression Scale: > 10), and pain catastrophizing (Pain Catastrophizing Scale: > 31) were identified as complex cases. Patient outcomes; treatment satisfaction on the Patient Global Impression of Change (PGIC), pain relief (NRS), pain interference on the Brief Pain Inventory (BPI) and quality of life indicator General Perceived Health (GPH) were evaluated. Logistic regression analyzed if belonging to the complex cases showed modification in the outcome of the PGIC and GPH. Linear regression was observed if complex cases differed in average reduction in pain relief and interference compared to non-complex cases. RESULTS: 1637 patients were included, of which 345 (21.08%) were considered complex cases. The changes in scores of pain relief and BPI active subscale were not significantly different between groups. The BPI affective subscale had a different change in score (-0.509; p: 0.002). The complex cases had an odds ratio (OR) of 0.59 (95% confidence interval [CI]: 0.36-0.77) on treatment satisfaction compared to non-complex cases, and an OR of 0.28 (95% CI: 0.11-0.56) on the GPH. CONCLUSION: When treating patients with complex cases, desired treatment outcome(s) should be recognized by specialists and patients, as these may be less likely to occur.

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.

Comparison of conventional and cooled radiofrequency treatment of the genicular nerves versus sham procedure for patients with chronic knee pain: protocol for a multicentre, double-blind, randomised controlled trial (COGENIUS).

INTRODUCTION: The prevalence of chronic knee pain is increasing. Osteoarthritis (OA) and persistent postsurgical pain (PPSP) are two important causes of knee pain. Chronic knee pain is primarily treated with medications, physiotherapy, life-style changes and intra-articular infiltrations. A radiofrequency treatment (RF) of the genicular nerves is a therapeutical option for refractory knee pain. This study investigates the effectiveness and cost-effectiveness of conventional and cooled RF in patients suffering from chronic, therapy resistant, moderate to severe knee pain due to OA and PPSP. METHODS AND ANALYSIS: The COGENIUS trial is a double-blinded, randomised controlled trial with 2-year follow-up. Patients and outcome assessors are blinded. Patients will be recruited and treated in Belgium and the Netherlands. All PPSP after a total knee prothesis and OA patients (grades 2-4) will undergo a run-in period of 1-3 months where conservative treatment will be optimised. After the run-in period, 200 patient per group will be randomised to conventional RF, cooled RF or a sham procedure following a 2:2:1 ratio. The analysis will include a comparison of the effectiveness of each RF treatment with the sham procedure and secondarily between conventional and cooled RF. All comparisons will be made for each indication separately. The primary outcome is the Western Ontario and McMaster Universities Osteoarthritis Index score at 6 months. Other outcomes include knee pain, physical functionality, health-related quality of life, emotional health, medication use, healthcare and societal cost and adverse events up to 24 months postintervention. ETHICS AND DISSEMINATION: Ethics approval was obtained from the Ethics Committee of the University of Antwerp (Number Project ID 3069-Edge 002190-BUN B3002022000025), the Ethics committee of Maastricht University (Number NL80503.068.22-METC22-023) and the Ethics committee of all participating hospitals. Results of the study will be published in international peer-reviewed journals. TRIAL REGISTRATION NUMBER: NCT05407610.

2. Cervical radicular pain.

INTRODUCTION: Cervical radicular pain is pain perceived in the upper limb, caused by irritation or compression of a cervical spine nerve, the roots of the nerve, or both. METHODS: The literature on the diagnosis and treatment of cervical radicular pain was retrieved and summarized. RESULTS: The diagnosis is made by combining elements from the patient's history, physical examination, and supplementary tests. The Spurling and shoulder abduction tests are the two most common examinations used to identify cervical radicular pain. MRI without contrast, CT scanning, and in some cases plain radiography can all be appropriate imaging techniques for nontraumatic cervical radiculopathy. MRI is recommended prior to interventional treatments. Exercise with or without other treatments can be beneficial. There is scant evidence for the use of paracetamol, nonsteroidal anti-inflammatory drugs, and neuropathic pain medications such as gabapentin, pregabalin, tricyclic antidepressants, and anticonvulsants for the treatment of radicular pain. Acute and subacute cervical radicular pain may respond well to epidural corticosteroid administration, preferentially using an interlaminar approach. By contrast, for chronic cervical radicular pain, the efficacy of epidural corticosteroid administration is limited. In these patients, pulsed radiofrequency treatment adjacent to the dorsal root ganglion may be considered. CONCLUSIONS: There is currently no gold standard for the diagnosis of cervical radicular pain. There is scant evidence for the use of medication. Epidural corticosteroid injection and pulsed radiofrequency adjacent to the dorsal root ganglion may be considered. [Correction added on 12 June 2023, after first online publication: The preceding sentence was corrected.].

Intrathecal drug delivery in the management of chronic pain.

Targeted intrathecal drug delivery (TIDD) has the objective of bringing the drug(s) close to the receptors influencing pain modulation, and thus reducing the dose and the side effects. Intrathecal drug delivery knew its real start with the development of permanent implantation of intrathecal and epidural catheters, combined with internal or external ports, reservoirs, and programmable pumps. TIDD is a valuable treatment for patients with cancer suffering refractory pain. Patients suffering noncancer-related pain should only be considered for TIDD when all other options have been tested, including spinal cord stimulation. Only two drugs are approved by the US Food and Drug Administration for TIDD administration for chronic pain: morphine and ziconotide as monotherapy. In pain management, off-label use of medication and combination therapy is often reported. The specific action of the intrathecal drugs, the efficacy and safety, is described, as well as the modalities for trialing intrathecal drug delivery and the implantation methods.

Comparison of cooled versus conventional radiofrequency treatment of the genicular nerves for chronic knee pain: a multicenter non-inferiority randomized pilot trial (COCOGEN trial).

BACKGROUND: Radiofrequency (RF) treatment of the genicular nerves has the potential to reduce chronic knee pain due to osteoarthritis or persistent postsurgical pain, however, a direct comparison between the two main modalities used, conventional and cooled, is lacking. METHODS: This double blind, non-inferiority, pilot, randomized controlled trial compared the effects of cooled and conventional RF in chronic knee pain patients suffering from osteoarthritis or persistent postsurgical pain after total knee arthroplasty. Patients were randomized following a 1:1 rate. The primary outcome was the proportion of patients with ≥50% pain reduction at 3 months postintervention. Other outcomes were knee pain, functionality, quality of life, emotional health, and adverse events up to 6 months postintervention. Conventional RF treatment was tested for non-inferiority to cooled in reducing knee pain at 3 months follow-up. RESULTS: Forty-nine of 70 patients were included, of which 47 completed a 3-month follow-up. The primary outcome was achieved in 4 of 23 patients treated with conventional RF (17%) vs in 8 of 24 with cooled (33%) (p=0,21). Results from the non-inferiority comparison were inconclusive in relation to the non-inferiority margin. There was no statistically significant difference between secondary outcomes. There were no serious adverse events. CONCLUSIONS: Both conventional and cooled RF treatment reduced pain in the osteoarthritis and persistent postsurgical pain population. This pilot study did not demonstrate statistically significant differences in the proportion of patients experiencing ≥50% pain reduction between techniques. The non-inferiority analysis was inconclusive. These results warrant further research. TRIAL REGISTRATION NUMBER: NCT03865849.

Long-Term Evaluation of Spinal Cord Stimulation in Patients With Painful Diabetic Polyneuropathy: An Eight-to-Ten-Year Prospective Cohort Study.

OBJECTIVE: This study aimed to evaluate the long-term effects of spinal cord stimulation (SCS) in patients with painful diabetic polyneuropathy (PDPN). MATERIALS AND METHODS: This prospective cohort study was the eight-to-ten-year follow-up of a previously performed pilot and randomized controlled trial on the effects of SCS in PDPN, initiated by the multidisciplinary pain center of Maastricht University Medical Center+. The study population consisted of a subgroup of patients who still used SCS treatment ≥ eight years after implantation (n = 19). Pain intensity scores (numeric rating scale [NRS]) during the day and night and data on secondary outcomes (ie, quality of life, depression, sleep quality) were reported during yearly follow-up consultations. Long-term efficacy of SCS was analyzed by comparing the most recently obtained data eight to ten years after implantation with those obtained at baseline. RESULTS: Pain intensity, day and night, was significantly (p < 0.01) reduced by 2.3 (NRS 6.6-4.3) and 2.2 (NRS 6.8-4.6) points, respectively, when comparing the long-term data with baseline. Moreover, for > 50% of patients, the pain reduction was > 30%, which is considered clinically meaningful. No differences were found regarding the secondary outcomes. CONCLUSION: This eight-to-ten-year follow-up study indicates that SCS can remain an effective treatment in the long term to reduce pain intensity in a subcohort of patients with PDPN who still had an SCS device implanted after eight years.