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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., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2024. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Competing Interests: Competing interests: None declared.

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., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2023. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background: The past two decades have witnessed a surge in the use of cervical spine joint procedures including joint injections, nerve blocks and radiofrequency ablation to treat chronic neck pain, yet many aspects of the procedures remain controversial., Methods: In August 2020, the American Society of Regional Anesthesia and Pain Medicine and the American Academy of Pain Medicine approved and charged the Cervical Joint Working Group to develop neck pain guidelines. Eighteen stakeholder societies were identified, and formal request-for-participation and member nomination letters were sent to those organizations. Participating entities selected panel members and an ad hoc steering committee selected preliminary questions, which were then revised by the full committee. Each question was assigned to a module composed of 4-5 members, who worked with the Subcommittee Lead and the Committee Chairs on preliminary versions, which were sent to the full committee after revisions. We used a modified Delphi method whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chairs, who incorporated the comments and sent out revised versions until consensus was reached. Before commencing, it was agreed that a recommendation would be noted with >50% agreement among committee members, but a consensus recommendation would require ≥75% agreement., Results: Twenty questions were selected, with 100% consensus achieved in committee on 17 topics. Among participating organizations, 14 of 15 that voted approved or supported the guidelines en bloc, with 14 questions being approved with no dissensions or abstentions. Specific questions addressed included the value of clinical presentation and imaging in selecting patients for procedures, whether conservative treatment should be used before injections, whether imaging is necessary for blocks, diagnostic and prognostic value of medial branch blocks and intra-articular joint injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for designating a block as positive, how many blocks should be performed before radiofrequency ablation, the orientation of electrodes, whether larger lesions translate into higher success rates, whether stimulation should be used before radiofrequency ablation, how best to mitigate complication risks, if different standards should be applied to clinical practice and trials, and the indications for repeating radiofrequency ablation., Conclusions: Cervical medial branch radiofrequency ablation may provide benefit to well-selected individuals, with medial branch blocks being more predictive than intra-articular injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of false-negatives (ie, lower overall success rate). Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice., Competing Interests: Competing interests: SPC has served as a consultant for Avanos, SPR, Releviate, Persica and Scilex in the past 3 years. ZLM receives research funding from Avanos. Anuj Bhatia receives research funding from Medtronic and consults for Bioventus. DAP has consulted for Avanos, Boston Scientific, Heron, Medtronic, Wise and Nevro. He has received research support from Avanos, Medtronic, Nevro, Stimgenics, and Abbott. DWL has served as a member of the Abbott speaker’s bureau. WMH receives funding from US WorldMeds. BJS is a consultant for State Farm and AIM Specialty Health. NK served on an advisory board for Bright Minds Biosciences, received research funding from Nevro Corporation, and received royalties from UpToDate. TD is a consultant for Abbott, Vertos, Axonics, Flowonix, SpineThera, Saluda Medical, Nalu, Medtronic, Nevro, SI Bone, Stimgenics, SPR Therapeutics, Cornerloc, Boston Scientific, PainTeq, Ethos, and Vertiflex; is a member of the advisory board for Abbott, Vertos, Flowonix, Nalu, SPR Therapeutics and Vertiflex; has stock options in Bioness, Vertiflex, Axonic, Vertos, SpineThera, Nalu, Cornerloc, PainTeq and SPR Therapeutics, and has common stock in Saluda Medical. He is a research consultant for Abbott, Vertos, Mainstay Medical, Saluda Medical, SPR Therapeutics, Boston Scientific and Vertiflex, and has a patent pending for the dorsal root ganglion paddle lead with Abbott., (© American Society of Regional Anesthesia & Pain Medicine 2022. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Competing Interests: Competing interests: None declared.

Background: The innervation of the sacroiliac joint (SIJ) is complex, with a dual innervation originating from the lumbosacral plexus anteriorly as well as the sacral lateral branches posteriorly. Nociceptors are found in intra-articular structures as well as periarticular structures. In patients with SIJ pain, a fluoroscopy-guided SIJ injection is usually performed posteriorly into the bottom one-third of the joint with local anesthetic and corticosteroids, but this does not always reach all intra-articular structures. The correlation between a cranial contrast spread and clinical success is undetermined in patients with SIJ pain., Methods: In a tertiary referral pain center, electronic medical records of patients who underwent an SIJ injection were retrospectively analyzed. Only patients with at least three positive provocation maneuvers for SIJ pain were selected. Contrast images of the SIJ were classified as with or without cranial spread on fluoroscopy as a marker of intra-articular injection. Clinical success was defined as ≥50% improvement in the patient's global perceived effect after 3-4 weeks. The primary outcome was defined as the correlation between cranial contrast spread and clinical success after an SIJ injection., Results: 128 patients in total were included. In 68 patients (53.1%) fluoroscopy showed cranial contrast spread. Clinical success was higher in patients with cranial spread of contrast (55 of 68, 81%) versus those without (35 of 60, 58%) (p=0.0067). In a multivariable analysis with age, gender, presence of rheumatoid arthritis, side, and number of positive provocation maneuvers, the cranial spread of contrast remained the only independent factor of clinical success (p=0.006; OR 3.2, 95% CI 1.4 to 7.7)., Conclusion: In patients with SIJ pain, identified by positive pain provocation maneuvers, cranial contrast spread as a marker of intra-articular injection, with subsequent injection of 3 mL of local anesthetic and methylprednisolone 40 mg, was significantly correlated with clinical success up to 4 weeks. Therefore, attempts should be made to reach this final needle position before injecting local anesthetic and corticosteroids. This result needs to be confirmed in a high-quality prospective trial., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2021. No commercial re-use. See rights and permissions. Published by BMJ.)

Background and Objectives: Chronic pain affects many adults. To improve our daily practice, we need to understand multidisciplinary approaches, integrated treatment plans and the biopsychosocial context of these patients. To date, almost 15 000 chronic pain patients have been referred to the Maastricht University Pain Center in the Netherlands., Methods: This study describes 11 214 of these patients suffering from chronic pain. Chronic pain was analyzed using relevant Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials instruments., Results: Most patients were female (59.3%). The prevalence of low education was 59%, and unemployment/disability was 35.9%. The mean age was 55.6 years. Severe pain (Numerical Rating Sale score 7-10) was reported by 71.9% of the patients; psychological and quality of life values deteriorated when pain severity increased. Approximately 36% of patients showed severe signs of depression or anxiety, and 39% displayed high pain catastrophizing. Of all patients, 17.8% reported high values for pain severity, catastrophizing and anxiety or depression., Conclusions: Based on baseline biopsychosocial values, this study shows the complexity of patients referred to pain centers. Pain management with a biopsychosocial approach in an integrated multidisciplinary setting is indispensable. Above all, adjusted education on chronic pain and attention to its biopsychosocial aspects are deemed necessary., Competing Interests: Competing interests: None declared., (© American Society of Regional Anesthesia & Pain Medicine 2020. No commercial re-use. See rights and permissions. Published by BMJ.)

Background: The past two decades have witnessed a surge in the use of lumbar facet blocks and radiofrequency ablation (RFA) to treat low back pain (LBP), yet nearly all aspects of the procedures remain controversial., Methods: After approval by the Board of Directors of the American Society of Regional Anesthesia and Pain Medicine, letters were sent to a dozen pain societies, as well as representatives from the US Departments of Veterans Affairs and Defense. A steering committee was convened to select preliminary questions, which were revised by the full committee. Questions were assigned to 4-5 person modules, who worked with the Subcommittee Lead and Committee Chair on preliminary versions, which were sent to the full committee. We used a modified Delphi method, whereby the questions were sent to the committee en bloc and comments were returned in a non-blinded fashion to the Chair, who incorporated the comments and sent out revised versions until consensus was reached., Results: 17 questions were selected for guideline development, with 100% consensus achieved by committee members on all topics. All societies except for one approved every recommendation, with one society dissenting on two questions (number of blocks and cut-off for a positive block before RFA), but approving the document. Specific questions that were addressed included the value of history and physical examination in selecting patients for blocks, the value of imaging in patient selection, whether conservative treatment should be used before injections, whether imaging is necessary for block performance, the diagnostic and prognostic value of medial branch blocks (MBB) and intra-articular (IA) injections, the effects of sedation and injectate volume on validity, whether facet blocks have therapeutic value, what the ideal cut-off value is for a prognostic block, how many blocks should be performed before RFA, how electrodes should be oriented, the evidence for larger lesions, whether stimulation should be used before RFA, ways to mitigate complications, if different standards should be applied to clinical practice and clinical trials and the evidence for repeating RFA (see table 12 for summary)., Conclusions: Lumbar medial branch RFA may provide benefit to well-selected individuals, with MBB being more predictive than IA injections. More stringent selection criteria are likely to improve denervation outcomes, but at the expense of more false-negatives. Clinical trials should be tailored based on objectives, and selection criteria for some may be more stringent than what is ideal in clinical practice., Competing Interests: Competing interests: TD: consultant for Abbott, Axonics, Nalu, Saluda, Medtronic, Vertiflex (Boston Scientific), Nevro, Vertos, Vertiflex, SPR. Funded research: Vertiflex, Vertos, Abbott, Saluda, SPR. Minor Equity: Bioness, Vertiflex, Vertos, Saluda, SPR. SPC: funded research: Avanos Consultant: Abbott, Medtronic, Boston Scientific David Provenzano: consultant for Avanos, Boston Scientific, Medtronic, Nevro, Esteve and Salix Research support: Medtronic, Nevro, Stimgenics and Abbott., (© American Society of Regional Anesthesia & Pain Medicine 2020. Re-use permitted under CC BY-NC. No commercial re-use. Published by BMJ.)

Background and Objectives: Radiofrequency ablation of genicular nerves has proved to be successful in relieving pain and incapacity caused by osteoarthritis of the knee. However, long-term efficacy of such a treatment remains to be assessed. The current study aimed to reproduce radiofrequency neurotomy of genicular nerves to manage gonarthrosis pain and disability and establish therapeutic response until 1 year after intervention., Methods: This single-center, prospective, observational, noncontrolled, longitudinal study included patients with grade 3 to 4 gonarthrosis suffering from intractable knee pain, scoring 5 or more on the visual analog scale (VAS) during >6 months. Therapy was based on ultrasound guided radiofrequency neurotomy of the superior medial, superior lateral and inferior medial genicular nerves. Visual analog scale and Western Ontario and McMaster Universities Osteoarthritis scores were assessed before therapy and at 1, 6, and 12 months following treatment., Results: Radiofrequency neurotomy of genicular nerves significantly reduced perceived pain (VAS) and disability (Western Ontario and McMaster Universities Osteoarthritis) in the majority of participants, without untoward events. The proportion of participants with improvement of 50% or greater in pretreatment VAS scores at 1, 6, and 12 months following intervention were 22/25 (88%), 16/25 (64%) and 8/25 (32%), respectively., Conclusions: Ultrasound-guided radiofrequency neurotomy of genicular nerves alleviates intractable pain and disability in the majority of patients with advanced osteoarthritis of the knee. Such a treatment is safe and minimally invasive and can be performed in an outpatient setting. The beneficial effect of treatment started to decline after 6 months, but even 1 year after the intervention, 32% of patients reported 50% improvement or greater in pretreatment VAS scores.

Background and Objectives: Systematic reviews evaluate the utility of procedural interventions of the spine, including epidural steroid injections (ESIs). However, existing quality assessment tools either fail to account for proper technical quality and patient selection or are not validated. We developed and validated a simple scale for ESIs to provide a quality assessment and rating of technique for injections of the spine (AQUARIUS)., Methods: Seven experts generated items iteratively based on prior ESI technique studies and professional judgment. Following testing for face and content validity, a 17-item instrument was used by 8 raters from 2 different backgrounds to assess 12 randomized controlled trials, selected from 3 different categories. Using frequency of assessment, a 12-item instrument was also generated. Both instruments underwent reliability (intraclass correlation coefficient), validity (ability to distinguish "low," "random," and "high" study categories), and diagnostic accuracy (receiver operating characteristics) testing., Results: Both 17- and 12-item instruments were scored consistently by raters regardless of background, with overall intraclass correlation coefficients of 0.72 (95% confidence interval [CI], 0.53-0.89) and 0.71 (95% CI, 0.51-0.89), respectively. Both instruments discriminated between clinical trials from all 3 categories. Diagnostic accuracy was similar for the 2 instruments, with areas under receiver operating characteristic curves of 0.89 (95% CI, 0.82-0.96) and 0.90 (95% CI, 0.82-0.97), respectively., Conclusions: The instrument in both 17- and 12-item formats demonstrates good reliability and diagnostic accuracy in rating ESI studies. As a complement to other tools that assess bias, the instrument may improve the ability to evaluate evidence for systematic reviews and improve clinical trial design.

It is often said that regional anesthesia is the practice of applied anatomy. Therefore, it is fitting that on the occasion of his 500th birthday, we celebrate the life and work of the brilliant Flemish anatomist, Andreas Vesalius (1514-1564), the founder of modern anatomy.

Radicular pain is an important health care problem, with only limited evidence-based treatments available. Treatment selection should ideally target documented pathophysiological pathways. In herniated discs, a sequence in the inflammatory cascade can be observed that initiates and maintains increased nociceptive signal input. Inflammatory mediators including tumor necrosis factor α are released from the nucleus pulposus and the degenerating peripheral nerve, which, in turn, induces production of neurotrophins like nerve growth factor and brain-derived neurotrophic factor. Neurotrophins interfere not only with the generation of ectopic firing of nociceptive neurons in the dorsal root ganglion but also with the excitability and sensitization of neuronal transmission in the dorsal spinal horn. Radicular pain is further characterized by the electrophysiological spreading of the afferent nociceptive input over different spinal nerve roots. Both the complex pathophysiological pathways involved and the spreading of the nociceptive signal make radicular pain difficult to treat. Pulsed radiofrequency (PRF) is considered an option in treatment of radicular pain. To understand and increase the efficiency of PRF interventional treatments in radicular pain, both in vitro and in vivo studies aiming at elucidating part of the mechanism of action of PRF are described. Potential factors that may improve the efficacy of PRF treatment in radicular pain are discussed.

Background: In animal models of neuropathic pain (NP), promising results have been reported with the administration of minocycline, possibly through inhibition of spinal brain-derived neurotrophic factor (BDNF) expression. No data are available on the effect of amitriptyline and gabapentin on spinal BDNF expression. If the mechanism of action of the latter drugs does not involve brain-derived NP inhibition, further clinical research in BDNF is warranted., Methods: In this placebo-controlled study, we investigated the effects of amitriptyline (5 mg/kg), gabapentin (50 mg/kg), and minocycline (25 mg/kg) twice a day on NP behavior in a sciatic chronic constriction injury (CCI) rat model. Drug treatment started 7 days after CCI and lasted 14 days. At postoperative day 21, spinal BDNF expression in laminae I and II was quantified using immunocytochemistry., Results: Sciatic CCI resulted in NP behavior throughout the duration of the experiment in the placebo group. When administered for 2 weeks, minocycline (P ≤ 0.001) and amitriptyline (P ≤ 0.05), but not gabapentin, reduced thermal hyperalgesia. None of these drugs reduced mechanical allodynia. As opposed to amitriptyline and gabapentin, 2 weeks of treatment with minocycline reduced brain-derived, neurotrophic factor immunoreactivity (P ≤ 0.05) in the ipsilateral dorsal horn., Conclusions: Minocycline and amitriptyline both reduce NP behavior in a sciatic CCI rat model, but only minocycline reduces spinal BDNF, indicating different modes of action of these 2 drugs. The observed actions of minocycline closely fit the clinical needs for the treatment of NP.

Background and Objectives: Occipital neuralgia is a paroxysmal nonthrobbing, stabbing pain in the area of the greater or lesser occipital nerve caused by irritation of these nerves. Although several therapies have been reported, no criterion standard has emerged. This study reports on the results of a prospective trial with 6 months of follow-up in which pulsed radiofrequency treatment of the greater and/or lesser occipital nerve was used to treat this neuralgia., Methods: Patients presenting with clinical findings suggestive of occipital neuralgia and a positive test block of the occipital nerves with 2 mL of local anesthetic underwent a pulsed radiofrequency procedure of the culprit nerves. Mean scores for pain, quality of life, and medication intake were measured 1, 2, and 6 months after the procedure. Pain was measured by the visual analog and Likert scales, quality of life was measured by a modified brief pain questionnaire, and medication intake was measured by a Medication Quantification Scale., Results: During a 29-month period, 19 patients were included in the study. Mean visual analog scale and median Medication Quantification Scale scores declined by 3.6 units (P = 0.002) and 8 units (P = 0.006), respectively, during 6 months. Approximately 52.6% of patients reported a score of 6 (pain improved substantially) or higher on the Likert scale after 6 months. No complications were reported., Conclusions: Pulsed radiofrequency treatment of the greater and/or lesser occipital nerve is a promising treatment of occipital neuralgia. This study warrants further placebo-controlled trials.

Cervical radicular pain affects 83 per 100,000 adults annually. Diagnosis by means of physical examination, imaging, and electrophysiological studies is characterized by high specificity but low sensitivity. In this review, we focus on the role of the dorsal root ganglion and those treatment modalities that aim at pathophysiological mechanisms occurring after injury to the dorsal root ganglion. Cervical nerve injury initiates multiple events that lead to changes in nerve function and result in spontaneous firing at the dorsal root ganglion. Among these, inflammation and changes in ion-channel function play a pivotal role. Although many treatment modalities are described in the literature, the available evidence for efficacy does not allow us to formulate definitive conclusions on the optimal therapy. A lack of evidence is reported for cervical spine surgery. Interlaminar epidural steroid administration and radiofrequency techniques adjacent to the cervical dorsal root ganglion have the highest, but still weak recommendations.