Bardoxolone Methyl Ameliorates Chemotherapy-Induced Neuropathic Pain by Activation of Phosphorylated Nuclear Factor Erythroid 2-Related Factor 2 in the Dorsal Root Ganglia.

BACKGROUND: Many chemotherapeutic drugs, including paclitaxel, produce neuropathic pain in patients with cancer, which is a dose-dependent adverse effect. Such chemotherapy-induced neuropathic pain (CINP) is difficult to treat with existing drugs. Nuclear factor erythroid 2-related factor 2 (Nrf2) is a major regulator of antioxidative responses and activates phosphorylated Nrf2 (pNrf2). We determined the analgesic effects of bardoxolone methyl (BM), an Nrf2 activator, and the role of pNrf2 on CINP. METHODS: CINP was induced in rats by intraperitoneally injecting paclitaxel on 4 alternate days in rats. BM was injected systemically as single or repeated injections after pain fully developed. RNA transcriptome, mechanical hyperalgesia, levels of inflammatory mediators and pNrf2, and location of pNrf2 in the dorsal root ganglia (DRG) were measured by RNA sequencing, von Frey filaments, Western blotting, and immunohistochemistry in rats and human DRG samples. In addition, the mitochondrial functions in 50B11 DRG neuronal cells were measured by fluorescence assay. RESULTS: Our RNA transcriptome of CINP rats showed a downregulated Nrf2 pathway in the pain condition. Importantly, single and repeated systemic injections of BM ameliorated CINP. Paclitaxel increased inflammatory mediators, but BM decreased them and increased pNrf2 in the DRG. In addition, paclitaxel decreased mitochondrial membrane potential and increased mitochondrial volume in 50B11 cells, but BM restored them. Furthermore, pNrf2 was expressed in neurons and satellite cells in rat and human DRG. CONCLUSIONS: Our results demonstrate the analgesic effects of BM by Nrf2 activation and the fundamental role of pNrf2 on CINP, suggesting a target for CINP and a therapeutic strategy for patients.

The efficacy of high-intensity laser therapy in wound healing: a narrative review.

High-intensity laser therapy (HILT) has recently been incorporated into wound management therapeutic protocols (Mosca RC et al. (2019) Photobiomodulation Therapy for Wound Care: A Potent, Noninvasive, Photoceutical Approach. Adv Skin Wound Care 32(4):157-167. https://doi.org/10.1097/01.ASW.0000553600.97572.d2 ). Laser therapy is increasingly used as an adjunct to therapeutic interventions in clinical practice (Dundar U et al. (2015) Effect of high-intensity laser therapy in the management of myofascial pain syndrome of the trapezius: a double-blind, placebo-controlled study. Lasers Med Sci 30(1):325-332. https://doi.org/10.1007/s10103-014-1671-8 ). This study aimed to evaluate the efficacy of HILT and the potential benefits of incorporating co- interventions alongside HILT in wound management. The following databases were searched up to April 2023: Embase, MEDLINE, PubMed, and Cinahl, as well as manual searches. The search keywords included high- intensity laser therapy, high-power laser therapy, laser therapy, wound, ulcer, and wound healing. The primary measures were decreased wound surface area (WSA) and improved wound appearance (WA) or other objective wound assessment tools containing these two values. Six human studies investigating HILT in wound healing treatment and one animal study assessing the wound-healing effects of HILT in acute wounds of mice were selected (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci.;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). This limited number of studies exhibited varying treatment parameters, blinding procedures, wound etiologies, irradiation protocols, and testing areas (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci. ;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). All selected studies demonstrated favorable results in improving wound conditions (Thabet AAE, Mahran HG, Ebid AA, Alshehri MA. Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci. ;30(4):570-575. doi:, Ebid AA, Thabet A, Helal O (2018) (2011) Efficacy of pulsed high intensity Nd: Yag Laser in Treatment of Chronic Diabetic Foot Ulcer. Energy for Health pp. 25-30); (Ebid AA, El-Kafy EM, Alayat MS (2013) Effect of pulsed Nd: YAG laser in the treatment of neuropathic foot ulcers in children with spina bifida: a randomized controlled study. Photomed Laser Surg 31(12):565-570. https://doi.org/10.1089/pho.2013.3533 ); (Hong SE et al. (2016) Effects of neodymium-yttrium-aluminum garnet (Nd: YAG) pulsed high-intensity laser therapy on full thickness wound healing in an experimental animal model. J Cosmet Laser Ther 18(8):432-437. https://doi.org/10.1080/14764172.2016.1202421 ); (Lu Q et al. (2021) Clinical effects of high-intensity laser therapy on patients with chronic refractory wounds: a randomised controlled trial. BMJ Open 11(7):e045866. https://doi.org/10.1136/bmjopen-2020-045866 ); (Pereira FLC et al. (2020) Use of a High-Power Laser for Wound Healing: A Case Report. J Lasers Med Sci 11(1):112-114. https://doi.org/10.15171/jlms.2020.19 ); (Thabet AAE et al. (2018) Effect of pulsed high intensity laser therapy on delayed caesarean section healing in diabetic women. J Phys Ther Sci 30(4):570-575. https://doi.org/10.1589/jpts.30.570 ); (Nussbaum EL, Baxter GD, Lilge L (2003) A Review of Laser Technology and Light-Tissue Interactions as a Background to Therapeutic Applications of Low Intensity Lasers and Other Light Sources. Phys Therapy Reviews 8(1):31-44. https://doi.org/10.1002/lsm.20769 ). Although insufficient data support using HILT in wound management, the promising results encourage further research. HILT appears effective in wound healing, but more high-quality studies are needed to identify optimal laser protocols.

The impact of scrambler therapy on pain and quality of life for chemotherapy-induced peripheral neuropathy: A pilot study.

BACKGROUND: Chemotherapy-induced peripheral neuropathy (CIPN) is a debilitating disturbance among patients who received chemotherapy, with no effective treatment available. Scrambler therapy (ST) is a noninvasive treatment capable of improving multiple quality-of-life symptoms beyond pain. We aimed to evaluate the efficacy of ST for pain and nonpain symptoms related to CIPN. METHODS: Ten patients with moderate to severe CIPN symptoms for >3 months were enrolled in a single-arm trial of ST for 10 daily sessions. CIPN-related symptoms were measured throughout the treatment period and up to 6 months thereafter. RESULTS: The worst pain was reduced by 6 months (p = 0.0039). QST demonstrated the greatest improvement in pressure of 60 g (p = 0.308, Cohen's d = 0.42) and cold temperature threshold of 2.5°C (p = 0.9375, Cohen's d = 0.51) in the gastrocnemius area. Symptoms of numbness, tingling, trouble walking, and disturbed sleep had significant improvements at 6 months. Pain medication use decreased by 70% at the end of treatment and by 42% at 6 months. Patient satisfaction was high (82%) and no adverse events with ST treatment were reported. CONCLUSIONS: The results of this pilot trial support the use of ST by demonstrating improvement in multiple domains of quality of life for CIPN patients during an extended follow-up of 6 months. However, further large-scale studies are needed to confirm our findings.

Scrambler therapy for noncancer neuropathic pain: a focused review.

PURPOSE OF REVIEW: Therapeutic methods for neuropathic are limited; available drugs can be inadequate or have adverse effects that compromise quality of life. Interest has grown in alternatives to pharmacologic therapy for neuropathic pain. We present a focused review of the literature about the relatively novel noninvasive, nonpharmacologic electrocutaneous nerve stimulation technique called scrambler therapy for treating noncancer neuropathic pain. RECENT FINDINGS: Neuromodulation techniques targeting peripheral sites have changed rapidly in recent years. Several clinical studies have demonstrated the analgesic effect of scrambler therapy after 10 sessions of treatment for various types of pain. Although scrambler therapy was originally used for cancer pain, its indications have broadened to postoperative pain, chemotherapy-induced peripheral neuropathy, postherpetic neuralgia, low back pain, diabetic neuropathy, complex regional pain syndrome and central pain syndrome. That said, some of the studies are controversial owing to their small sample size, lack of appropriate scrambler therapy protocol and possible lack of experience of the operators. SUMMARY: We present the historical perspective, mechanism of action and trial outcomes of scrambler therapy, representing an avenue for managing neuropathic pain without drugs. Well designed phase II/III clinical trials must be conducted to confirm the positive findings reported using scrambler therapy technology. If validated, scrambler therapy could be a game changer.

Update on cannabis and cannabinoids for cancer pain.

PURPOSE OF REVIEW: The prevalence of cancer pain will continue to rise as pain is common among the survivorship and general cancer population. As interest in cannabis and cannabinoids for medicinal use including pain management continues to rise, there is growing need to update and review the current state of evidence for their use. The literature was searched for articles in English with key words cannabis, cannabinoids, and cancer pain. The sources of articles were PubMed, Embase, and open Google search. RECENT FINDINGS: In a double-blind randomized placebo-controlled trial including a 3-week treatment period of nabiximol for advanced cancer patients with pain refractory to optimized opiate therapy, improvements in average pain were seen in the intention to treat population (P = 0.0854) and per- protocol population (P = 0.0378). SUMMARY: To date, preclinical data has demonstrated evidence to suggest promising potential for cancer pain and the urgent need to translate this into clinical practice. Unfortunately, due to limited data, for adults with advanced cancer being treated with opiate therapy, the addition of cannabis or cannabinoids is not currently supported to address cancer pain effectively.

The Effects of Agrin Isoforms on Diabetic Neuropathic Pain in a Rat Streptozotocin Model.

BACKGROUND: Diabetes mellitus affects 9.3% of the US population and increases risks of surgery and complications. Diabetic neuropathic pain (DNP), one of the main consequences of diabetes mellitus, is extremely difficult to treat. Current medications yield limited benefits and/or have severe adverse effects. Therefore, new, effective treatment is needed. METHODS: Streptozotocin at 55 mg/kg was injected intraperitoneally in rats to induce diabetes mellitus. Diabetic rats exhibiting neuropathic pain underwent intrathecal injection of purified agrin proteins at various doses and were then tested for tactile allodynia to evaluate whether DNP was inhibited. The agrin effects were also analyzed with patch-clamp recording on spinal cord slices. RESULTS: Fifty-kilo Dalton agrin (Agr50) at 0.2 and 2 ng suppressed DNP when given intrathecally, while 25- and 75-kDa agrin (Agr25, Agr75) had little effect. The suppressive effect of Agr50 lasted 4 hours after a single bolus injection. The difference in effects of Agr50 on mean withdrawal threshold (4.6 ± 2.2 g before treatment to 26 ± 0 g after treatment) compared with that of Agr25 (4.9 ± 2.0 g to 4.9 ± 2.0 g) and Agr75 (5.3 ± 2.3 g to 9.2 ± 2.5 g) was highly significant (P < .01). On spinal cord slices, Agr50 increased spontaneous GABAergic current activities, suggesting increased spontaneous inhibitory postsynaptic currents and action potential firing rate from GABA neurons, whereas Agr25 and Agr75 had no such effect. CONCLUSIONS: Agr50 had a potent suppressive effect on DNP and increased spontaneous inhibitory postsynaptic currents and action potential firing rate from GABA neurons. Therefore, Agr50 may provide a potential therapy for DNP.

Scrambler Therapy for the management of chronic pain.

PURPOSE: Chronic pain is a widespread and debilitating condition, encountered by physicians in a variety of practice settings. Although many pharmacologic and behavioral strategies exist for the management of this condition, treatment is often unsatisfactory. Scrambler Therapy is a novel, non-invasive pain modifying technique that utilizes trans-cutaneous electrical stimulation of pain fibers with the intent of re-organizing maladaptive signaling pathways. This review was conducted to further evaluate what is known regarding the mechanisms and mechanics of Scrambler Therapy and to investigate the preliminary data pertaining to the efficacy of this treatment modality. METHODS: The PubMed/Medline, SCOPUS, EMBASE, and Google Scholar databases were searched for all articles published on Scrambler Therapy prior to November 2015. All case studies and clinical trials were evaluated and reported in a descriptive manner. RESULTS: To date, 20 reports, of varying scientific quality, have been published regarding this device; all but one small study, published only as an abstract, provided results that appear positive. CONCLUSION: The positive findings from preliminary studies with Scrambler Therapy support that this device provides benefit for patients with refractory pain syndromes. Larger, randomized studies are required to further evaluate the efficacy of this approach.

Basic science and clinical management of painful and non-painful chemotherapy-related neuropathy.

Chemotherapy-induced peripheral neuropathy (CIPN) is a dose-limiting toxicity of several chemotherapeutics used in the treatment of all the most common malignancies. There are several defined mechanisms of nerve damage that take place along different areas of the peripheral and the central nervous system. Treatment is based on symptom management and there are several classes of medications found to be efficacious in the treatment of neuropathic pain. Neuropathic pain that persists despite appropriate pharmacotherapy may respond to interventional procedures that span a range of invasiveness. The purpose of this review article is to examine the basic science of neuropathy and currently available treatment options in the context of chemotherapy induced peripheral neuropathy.

The Analgesic Effect of Rolipram, a Phosphodiesterase 4 Inhibitor, on Chemotherapy-Induced Neuropathic Pain in Rats.

BACKGROUND: Chemotherapy-induced neuropathic pain is a significant side effect of chemotherapeutic agents. Currently, there are no effective analgesics for chemotherapy-induced neuropathic pain. Rolipram is a selective phosphodiesterase 4 inhibitor, which increases intracellular cyclic AMP in nerve and immune cells. The aim of our study was to determine the analgesic effects of rolipram on paclitaxel (PAC)-induced neuropathic pain in rats. METHODS: Chemotherapy-induced neuropathic pain was produced by intraperitoneal injection of PAC on 4 alternate days in male Sprague-Dawley rats. Mechanical allodynia was measured by using von Frey filaments. RESULTS: After the rats developed PAC-induced pain behavior (such as mechanical allodynia), a single intraperitoneal injection and continuous infusion of rolipram ameliorated PAC-induced pain behavior. In addition, systemic infusion of the drug during the early phase of developing pain behavior did not prevent the development of mechanical allodynia induced by PAC. CONCLUSIONS: These results suggest that rolipram alleviated mechanical allodynia induced by PAC in rats. Thus, phosphodiesterase 4 inhibitors may prove useful in the treatment of chemotherapy-induced neuropathic pain. However, further studies are needed to clarify their effects in clinical settings.

Brief review: pain management for cancer survivors: challenges and opportunities.

PURPOSE: As the number of cancer survivors continues to increase due to advances in medicine, many cancer survivors remain on their same pain management regimen long after their cancer treatment has been completed. Thus, the purpose of this review is to encourage awareness of the challenges and opportunities of pain management in cancer survivorship. It is our expectation that these patients will be referred to pain medicine specialists so their pain management can be optimized during the period of survivorship and ultimately improve their quality of life. PRINCIPAL FINDINGS: Cancer and its treatment can cause significant pain which requires multidrug therapy, including strong analgesics such as opioids. Optimal pain management has been shown to improve the quality of life of cancer patients, and that is also true for cancer survivors. Nevertheless, the appropriate use of pain medications, especially opioids, must be re-evaluated and adjusted during treatment as the patient transitions into survivorship care and thereafter. This may otherwise result in unnecessary opioid use or may even lead to abuse. Fortunately, as cancer treatment is completed and the survivorship period begins, pain improves gradually and the need for pain medication should decrease. Unfortunately, some patients continue to take their potent analgesics during the period of survivorship although it may not be necessary. It is a challenge for pain practitioners who do not see these patients early in their disease or in the recovery period. Nevertheless, this challenge presents an opportunity for pain management providers to educate oncologists to refer cancer survivors to pain centres early during the period of their survivorship. Cancer survivors could then receive optimal care and maintain a better quality of life without having to take unnecessary pain medications. CONCLUSIONS: It is clear that there is a need to improve pain management in cancer patients, particularly in cancer survivors. Pain physicians should play a critical role as part of a multidisciplinary team that cares not only for cancer patients but also for cancer survivors. Optimizing pain management during the cancer survivorship period results in a better quality of life.

Brief review: chemotherapy-induced painful peripheral neuropathy (CIPPN): current status and future directions.

PURPOSE: Chemotherapy-induced painful peripheral neuropathy (CIPPN) affects up to 90% of cancer patients treated with chemotherapy agents. Despite the fact that it is relatively common, the underlying pathophysiology is still unclear and its treatment remains generic. Mechanisms of CIPPN are multifactorial, dependent on the specific chemotherapeutic agent used, and include multiple patient-related factors, including genetic factors that may predispose patients to either develop or not develop CIPPN. The purpose of this article is to review mechanisms, clinical signs and symptoms, diagnosis, treatment options, and prognosis for patients who develop CIPPN. We also offer research considerations for this complex and unpredictable phenomenon. PRINCIPAL FINDINGS: Chemotherapeutic agents can damage the peripheral nervous system, including the nerve terminals, axons, cell body, and myelin sheath of sensory nerves. Herein, we describe some of the anatomical and functional changes that are thought to take place at various levels of the nervous system. On a clinical level, patients with CIPPN report multiple symptoms. It is essential to obtain an accurate history from the patient and to perform a thorough physical examination in order to obtain the patient's subjective perspective. Additionally, objective measurements may be needed in order to articulate clearly the effects of this complex syndrome and to ensure an accurate diagnosis, treatment, and prognosis. CONCLUSIONS: The management of CIPPN remains a clinical challenge for pain practitioners. As more research is being carried out to elucidate its pathophysiology and therapy, the innovative use of several non-traditional categories of drugs seems promising in the management of this complex phenomenon. Studies addressing predictability and possible genetic predisposition are necessary not only for preventive measures but also for targeted treatments.

Effectiveness of Facet Joint Nerve Blocks in Managing Chronic Axial Spinal Pain of Facet Joint Origin: A Systematic Review and Meta-Analysis.

BACKGROUND: Chronic axial spinal pain is one of the major causes of disability. Literature shows that spending on low back and neck pain and musculoskeletal disorders continues to escalate, not only with disability, but also with increasing costs, accounting for the highest amount of various disease categories. Based on the current literature utilizing controlled diagnostic blocks, facet joints, nerve root dura, and sacroiliac joints have been shown as potential sources of spinal pain. Therapeutic facet joint interventional modalities of axial spinal pain include radiofrequency neurotomy, therapeutic facet joint nerve blocks, and therapeutic intraarticular injections. OBJECTIVE: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of facet joint nerve blocks as a therapeutic modality in managing chronic axial spinal pain of facet joint origin. STUDY DESIGN: A systematic review and meta-analysis of randomized controlled trials (RCTs) and observational studies utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist. METHODS: The available literature on facet joint nerve blocks in axial spinal pain was reviewed. The quality assessment criteria utilized were the Cochrane review criteria to assess risk of bias, the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment (IPM-QRB) for randomized therapeutic trials, and the Interventional Pain Management Techniques - Quality Appraisal of Reliability and Risk of Bias Assessment for Nonrandomized Studies (IPM-QRBNR) for nonrandomized studies. The evidence was graded according to Grading of Recommendations, Assessment, Development, and Evaluation (GRADE) assessment criteria. The level of evidence was based on best evidence synthesis with modified grading of qualitative evidence from Level I to Level V. A comprehensive literature search of multiple databases from 1966 to July 2023, including manual searches of the bibliography of known review articles was performed. Quality assessment of the included studies and best evidence synthesis were incorporated into qualitative and quantitative evidence synthesis. OUTCOME MEASURES: The primary outcome measure was the proportion of patients with significant relief and functional improvement of greater than 50% of at least 3 months. Duration of relief was categorized as short-term (less than 6 months) and long-term (greater than 6 months). RESULTS: This assessment identified 8 high-quality and one moderate quality RCTs and 8 high quality and 4 moderate quality non-randomized studies with application of spinal facet joint nerve blocks as therapeutic modalities. However, based on the Grading of Recommendations, Assessment, Development and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability, with 11 studies showing moderate levels of GRADE evidence and clinical applicability. LIMITATIONS: Despite the availability of multiple studies, the paucity of literature is considered as the major drawback. Based on Grading of Recommendations, Assessment Development, and Evaluations (GRADE) assessment, only 3 of the 21 studies showed high levels of evidence and clinical applicability. CONCLUSION: Based on the present systematic review and meta-analysis with 9 RCTs and 12 non-randomized studies, the evidence is Level II with moderate to strong recommendation for therapeutic facet joint nerve blocks in managing spinal facet joint pain.

Use of corticosteroids for adult chronic pain interventions: sympathetic and peripheral nerve blocks, trigger point injections - guidelines from the American Society of Regional Anesthesia and Pain Medicine, the American Academy of Pain Medicine, the American Society of Interventional Pain Physicians, the International Pain and Spine Intervention Society, and the North American Spine Society.

BACKGROUND: There is potential for adverse events from corticosteroid injections, including increase in blood glucose, decrease in bone mineral density and suppression of the hypothalamic-pituitary axis. Published studies note that doses lower than those commonly injected provide similar benefit. METHODS: Development of the practice guideline was approved by the Board of Directors of American Society of Regional Anesthesia and Pain Medicine with several other societies agreeing to participate. The scope of guidelines was agreed on to include safety of the injection technique (landmark-guided, ultrasound or radiology-aided injections); effect of the addition of the corticosteroid on the efficacy of the injectate (local anesthetic or saline); and adverse events related to the injection. Based on preliminary discussions, it was decided to structure the topics into three separate guidelines as follows: (1) sympathetic, peripheral nerve blocks and trigger point injections; (2) joints; and (3) neuraxial, facet, sacroiliac joints and related topics (vaccine and anticoagulants). Experts were assigned topics to perform a comprehensive review of the literature and to draft statements and recommendations, which were refined and voted for consensus (≥75% agreement) using a modified Delphi process. The United States Preventive Services Task Force grading of evidence and strength of recommendation was followed. RESULTS: This guideline deals with the use and safety of corticosteroid injections for sympathetic, peripheral nerve blocks and trigger point injections for adult chronic pain conditions. All the statements and recommendations were approved by all participants after four rounds of discussion. The Practice Guidelines Committees and Board of Directors of the participating societies also approved all the statements and recommendations. The safety of some procedures, including stellate blocks, lower extremity peripheral nerve blocks and some sites of trigger point injections, is improved by imaging guidance. The addition of non-particulate corticosteroid to the local anesthetic is beneficial in cluster headaches but not in other types of headaches. Corticosteroid may provide additional benefit in transverse abdominal plane blocks and ilioinguinal/iliohypogastric nerve blocks in postherniorrhaphy pain but there is no evidence for pudendal nerve blocks. There is minimal benefit for the use of corticosteroids in trigger point injections. CONCLUSIONS: In this practice guideline, we provided recommendations on the use of corticosteroids in sympathetic blocks, peripheral nerve blocks, and trigger point injections to assist clinicians in making informed decisions.

Nurse-Administered Auricular Point Acupressure for Cancer-Related Pain.

PURPOSE: The study aimed to (1) examine the feasibility of providing a training course on auricular point acupressure (APA) for clinical oncology nurses to integrate APA into real-world nursing care settings, and (2) examine the effectiveness of APA on cancer-related pain (CRP) under usual inpatient oncology ward conditions. METHODS: This was a 2-phase feasibility study. Phase 1, an in-person, 8 hour training program was provided to oncology nurses. Phase 2, a prospective and feasibility study was conducted to evaluate the integration of APA into nursing care activities to manage CRP. Oncology patients were included if their pain was rated at ≥4 on a 0 to 10 numeric rating scale in the past 24 hours. Patients received 1 APA treatment administered by the nurses and were instructed to stimulate the points for 3 days. Study outcomes (pain intensity, fatigue, and sleep disturbance), pain medication use, and APA practice were measured by a phone survey daily. RESULTS: Ten oncology nurses received APA training in phase 1. APA had been added to the hospital's electronic health records (EHRs) as a pain treatment. In phase 2, 33 oncology patients received APA treatment with a 100% adherence rate (pressing the seeds 3 times per day, 3 minutes per time based on the suggestion). The side effects of APA were minimal (~8%-12% felt tenderness on the ear). After 3 days of APA, patients reported 38% pain relief, 39% less fatigue, and 45% improvement in sleep disturbance; 24% reduced any type of pain medication use and 19% reduced opioid use (10 mg opioids using milligram morphine equivalent). The major barrier to integrating APA into routine nursing practice was time management (how to include APA in a daily workflow). CONCLUSION: It is feasible to provide 8-hour training to oncology nurses for mastering APA skill and then integrating APA into their daily nursing care for patients with CRP. Based on the promising findings (decreased pain, improved fatigue and sleep disturbance, and less opioid use), the next step is to conduct a randomized clinical trial with a larger sample to confirm the efficacy of APA for oncology nurses to treat CRP in real-world practice.ClinicalTrial.gov identifier number: NCT04040140.

The Influence of COVID-19 on Utilization of Epidural Procedures in Managing Chronic Spinal Pain in the Medicare Population.

STUDY DESIGN: A retrospective cohort study of utilization patterns and variables of epidural injections in the fee-for-service (FFS) Medicare population. OBJECTIVES: To update the utilization of epidural injections in managing chronic pain in the FFS Medicare population, from 2000 to 2020, and assess the impact of COVID-19. SUMMARY OF BACKGROUND DATA: The analysis of the utilization of interventional techniques also showed an annual decrease of 2.5% per 100,000 FFS Medicare enrollees from 2009 to 2018, contrasting to an annual increase of 7.3% from 2000 to 2009. The impact of the COVID-19 pandemic has not been assessed. METHODS: This analysis was performed by utilizing master data from the Centers for Medicare and Medicaid Services, physician/supplier procedure summary from 2000 to 2020. The analysis was performed by the assessment of utilization patterns using guidance from Strengthening the Reporting of Observational Studies in Epidemiology. RESULTS: Epidural procedures declined at a rate of 19% per 100,000 Medicare enrollees in the FFS Medicare population in the United States from 2019 to 2020, with an annual decline of 3% from 2010 to 2019. From 2000 to 2010, there was an annual increase of 8.3%. This analysis showed a decline in all categories of epidural procedures from 2019 to 2020. The major impact of COVID-19, with closures taking effect from April 1, 2020, through December 31, 2020, will be steeper and rather dramatic compared with April 1 to December 31, 2019. However, monthly data from the Centers for Medicare and Medicaid Services is not available as of now. Overall declines from 2010 to 2019 showed a decrease for cervical and thoracic transforaminal injections with an annual decrease of 5.6%, followed by lumbar interlaminar and caudal epidural injections of 4.9%, followed by 1.8% for lumbar/sacral transforaminal epidurals, and 0.9% for cervical and thoracic interlaminar epidurals. CONCLUSION: Declining utilization of epidural injections in all categories was exacerbated to a decrease of 19% from 2019 to 2020, related, in part, to the COVID-19 pandemic. This followed declining patterns of epidural procedures of 3% overall annually from 2010 to 2019.

A Systematic Review and Meta-analysis of the Effectiveness of Radiofrequency Neurotomy in Managing Chronic Neck Pain.

BACKGROUND: Extensive research into potential sources of neck pain and referred pain into the upper extremities and head has shown that the cervical facet joints can be a potential pain source confirmed by precision, diagnostic blocks. STUDY DESIGN: Systematic review and meta-analysis utilizing the Preferred Reporting Items for Systematic Reviews and Meta-Analyses (PRISMA) checklist, quality assessment of the included studies, conventional and single-arm meta-analysis, and best evidence synthesis. OBJECTIVE: The objective of this systematic review and meta-analysis is to evaluate the effectiveness of radiofrequency neurotomy as a therapeutic cervical facet joint intervention in managing chronic neck pain. METHODS: Available literature was included. Methodologic quality assessment of studies was performed from 1996 to September 2021. The level of evidence of effectiveness was determined. RESULTS: Based on the qualitative and quantitative analysis with single-arm meta-analysis and Grading of Recommendations, Assessment, Development and Evaluations (GRADE) system of appraisal, with inclusion of one randomized controlled trial (RCT) of 12 patients in the treatment group and eight positive observational studies with inclusion of 589 patients showing positive outcomes with moderate to high clinical applicability, the evidence is level II in managing neck pain with cervical radiofrequency neurotomy. The evidence for managing cervicogenic headache was level III to IV with qualitative analysis and single-arm meta-analysis and GRADE system of appraisal, with the inclusion of 15 patients in the treatment group in a positive RCT and 134 patients in observational studies. An overwhelming majority of the studies produced multiple lesions. LIMITATIONS: There was a paucity of literature and heterogeneity among the available studies. CONCLUSION: This systematic review and meta-analysis shows level II evidence with radiofrequency neurotomy on a long-term basis in managing chronic neck pain with level III to IV evidence in managing cervicogenic headaches.

Current Understanding of Phantom Pain and its Treatment.

BACKGROUND: Phantom limb pain (PLP), defined as a painful sensation in a portion of the body that has been amputated, occurs in upwards of 80% of limb amputees and can significantly impact a patient's quality of life. First hypothesized in 1551, the disease has been poorly understood for much of this time. Still today, the exact etiology of the condition is yet to be elucidated. In the periphery, PLP resembles the neuronal changes seen in other neuropathic pain conditions. However, in the central nervous system (CNS), imaging studies suggest changes unique to PLP, such as cortical reorganization. Despite a growing understanding of its underpinnings, a mechanism-based treatment is not yet available. Rather, a plethora of treatment methodologies are available with varying levels of supporting evidence and many treatments being utilized based on efficacy seen in non-PLP patients. OBJECTIVES: In this review, we provide a thorough summary of the current literature regarding PLP's etiology, diagnosis, treatment, and attempts to prevent the development of PLP following amputation. STUDY DESIGN: A narrative review. METHODS: This was a narrative review conducted after an extensive and thorough review of available literature on the topic from a variety of sources. RESULTS: Current evidence supports a central reorganization process with potential amplification of aberrant peripheral inputs as the etiology of PLP. This conclusion is supported by functional neuroimaging as well as the failure of peripherally focused treatments. Treatment of PLP remains difficult due to varying response rates to therapies. Nonetheless, there are several treatment modalities that have proven effective in the majority of patients tested, ranging from noninvasive systemic pharmacotherapy to more invasive neuromodulation, such as spinal cord stimulation. While opioid therapy remains the most evidence-based treatment, the newer neuromodulation techniques appear to be superior in symptom reduction with minimal side effects. LIMITATIONS: Evidence for the treatment of PLP is largely restricted to uncontrolled case reports and/or small single-site uncontrolled case series. Some research is further hampered by the presence of confounding factors such as concurrent treatment regimens. CONCLUSIONS: While PLP remains a difficult-to-treat condition, practitioners can greatly improve the quality of life of patients suffering from the condition with a wide range of developing treatments. For pain intractable to traditional pharmacologic treatment, neuromodulation therapies have proven to be highly effective with minimal side effect profiles.