Sustained Pain Reduction Research Articles

Characteristics in patients with very early therapeutic response of condoliase chemonucleolysis for lumbar disc herniation.

Treatment of lumbar disc herniation (LDH) using condoliase chemonucleolysis (CC) requires more time than surgery to demonstrate therapeutic effects. This study aimed to identify patients who show significant improvement in leg pain very early after CC and to determine pretreatment factors that can predict a very early therapeutic response. The study included 52 patients who underwent CC for treatment-resistant LDH. Scores for low back and leg pain measured by a numerical rating scale were assessed at four time points (1day, 1 week, 1 month, and 3 months after CC). Patients who reported subjective pain relief the day after treatment and further exhibited an improved straight leg raising (SLR) angle compared to pretreatment were classified as "very early responders (VER)". Of the 52 patients, 39 (75%) were VER, and 13 (25%) were non-VER. The VER showed earlier improvement in leg pain. The VER had a significantly higher proportion of positive SLR test patients (p = 0.01) and a significantly smaller pretreatment SLR angle compared to the non-VER (VER vs. non-VER: 40.6 ± 19.0 vs. 63.1 ± 16.9, p < 0.001). There were no significant differences in the level, type, and size of LDH and the disc regression rate between the two groups. Patients with a smaller pretreatment SLR angle are more likely to experience very early or early symptomatic relief, with a significant and sustained reduction in leg pain up to 3 months after CC treatment.

Efficacy of botulinum toxin injection using the right-sided unilateral retrocrural approach for celiac plexus in a cancer survivor with persistent abdominal pain: a case report.

Cancer survivors often face persistent abdominal pain, necessitating optimal pain management. While celiac plexus block (CPB) and botulinum toxin (BT) injection are viable options, traditional methods may encounter challenges due to patient-specific concerns and anatomical complexities. Here, the case of a cancer survivor in his 70 s experiencing recurrent abdominal pain, who declined conventional percutaneous CPB approaches due to anxiety related to aortic puncture, is presented. Following a pancreaticoduodenectomy, the patient developed chronic abdominal pain attributed to adhesions leading to small bowel obstruction. Concurrently, there was notable psychological distress, including anxiety, depression, and heightened concerns regarding tumor recurrence. Considering the patient's specific concerns, a right-sided unilateral retrocrural single-needle technique was proposed, aimed at alleviating pain, while avoiding conventional CPB approaches. Initial right-sided retrocrural CPB offered short-term relief, prompting a subsequent BT injection using the same approach. Following BT injection, the patient reported significant and sustained pain reduction (from 8 to 1 on an 11-point numerical rating scale) at both 12 and 20 weeks post-procedure. Right-sided retrocrural BT injection offers an alternative approach, addressing patient concerns and demonstrating prolonged pain relief. This may benefit cancer survivors with upper abdominal pain, emphasizing the importance of personalized and innovative pain management strategies.

Efficacy of scrambler therapy in chronic neuropathic pain: pairwise and dose-response meta-analysis

Chronic neuropathic pain (CNP) affects 7% of the world’s population and is challenging to control since existing medications are inadequate and have negative effects. Electrocutaneous devices, such as scrambler therapy (ST), have emerged as a possible option and have shown promising results in multiple randomized controlled trials (RCTs). However, the long-term efficacy of ST remains unknown. We aimed to evaluate the efficacy of ST in CNP reduction over time. We used the data sources including PubMed, Embase, Scopus, and Cochrane Central Register of Controlled Trials from inception to September 2023. Five placebo and three routine-care controlled RCTs were selected among the screened abstracts. Two authors independently extracted the data. Data was pooled using a model under the common parameters assumption. The studies were evaluated for methodological quality using the MethodologicAl STandard for Epidemiological Research (MASTER) scale. The primary outcome measure was pain reduction; pain was converted to a common 0 to 10 scale, and a weighted mean difference of more than 2 points on a 10-point pain scale was considered clinically important. Eight RCTs that evaluated the effect of ST on CNP were included, with a total sample size of 350 participants. None of the participants withdrew in all these trials owing to adverse events or lack of efficacy. There was high-quality evidence that ST reduced pain in the short term, with a mean difference of –3 points. The dose-response meta-analysis demonstrated a significant reduction in pain scores post-treatment, with a peak reduction at day 40. The effect of ST remained below the baseline values for 90 days, although with limited certainty. This study is the first dose-response meta-analysis to assess the duration of efficacy of ST in the treatment of CNP. The results demonstrated a clinically significant and more sustained reduction in pain created by ST compared to conventional treatments. Our findings indicate that ST could be used as a safe and effective alternative for managing CNP.

Exploring the therapeutic potential of ethanol extract of Erythrina fusca Lour. roots as an analgesic, antipyretic, and anti-inflammatory agent in experimental animals

Erythrina fusca Lour., renowned in traditional medicine for its soothing, analgesic, anti-inflammatory, and neuroinhibitory properties, is the focus of our investigation. Expanding on its traditional applications, we assessed the analgesic, anti-inflammatory, and antipyretic characteristics of the ethanol extract from E. fusca root (REEF). Administered orally to mice at varying doses (50, 100, and 150 mg/kg for pain and fever reduction; 100, 150, and 200 mg/kg for anti-inflammatory experiments), REEF's effects were systematically evaluated through parameters such as reaction time, pain inhibition ratio, COX2 and PGE2 levels, rectal temperature, fever inhibition ratio, paw diameter, paw edema inhibition ratio, and inflammatory cytokines. Results reveal that REEF consistently reduced licking and biting time (p &lt; 0.05) in response to formalin-induced pain in mice. Particularly noteworthy was the more pronounced reduction in COX2 and PGE2 during the late phase, with the most significant decrease observed at the 150 mg/kg REEF treatment (p &lt; 0.05). The licking time graph substantiated the analgesic efficacy of REEF, illustrating simultaneous and sustained pain reduction over time. Moreover, REEF significantly alleviated fever (p &lt; 0.05) in mice, with the most substantial effect observed three hours post-yeast injection. REEF not only efficiently reduced body temperature but also countered the fever-inducing effects of yeast at evaluated time points (p &lt; 0.05). In the context of carrageenan-induced inflammation, paw swelling markedly diminished after 4 and 5 hours (p &lt; 0.05). Notably, at the 5-hour mark, REEF treatment at 150 mg/kg dose exhibited significantly superior anti-inflammatory effects (p &lt; 0.05). Additionally, mice treated with REEF (100, 150, and 200 mg/kg) exhibited a considerable decrease (p &lt; 0.05) in serum concentrations of TNF-?, IL-1?, and IL-6 compared to the control treatment. The ethanol extract from Erythrina fusca roots demonstrates substantial potential for pain relief, fever reduction, and anti-inflammatory effects, positioning it as a promising herbal resource for the research and development of natural medicinal products with these therapeutic properties.

Impact of relugolix combination therapy on functioning and quality of life in women with endometriosis-associated pain

To evaluate the effect of relugolix combination therapy (relugolix CT; 40 mg relugolix, 1 mg estradiol, and 0.5 mg norethisterone acetate) for up to 2 years in the SPIRIT long-term extension study on functioning and health-related quality of life (QoL), using the Endometriosis Health Profile (EHP)-30 questionnaire, and assess how changes in QoL domains correlated with improvements in dysmenorrhea as well as nonmenstrual pelvic pain (NMPP). Long-term extension study of the SPIRIT phase 3 trials. Clinics and University Hospitals. Premenopausal women with moderate-to-severe endometriosis pain who previously completed the randomized SPIRIT trials were eligible to enroll in an 80-week long-term extension where all women received relugolix CT. Relugolix CT (relugolix 40 mg, estradiol 1 mg, and norethindrone acetate 0.5 mg). Least squares (LS) mean changes in the EHP-30 domain and total scores from baseline (pivotal) were analyzed using a mixed-effects model. Results up to 104 weeks are reported by a pivotal trial treatment group with a focus on the relugolix CT group (i.e., relugolix CT or placebo for 24 weeks, or delayed relugolix CT [relugolix 40 mg monotherapy for 12 weeks, followed by relugolix CT for 12 weeks]). In addition, the relationships between changes in dysmenorrhea and NMPP as well as changes in EHP-30 scores were assessed. In the 277 women treated with relugolix CT, LS mean EHP-30 pain domain scores improved by 57.8% (LS mean change: -32.8; 95% CI: -35.5, -30.1), 66.4% (LS mean change: -37.7; 95% CI: -40.3, -35.0), and 72.2% (LS mean change: -41.3; 95% CI: -43.9, -38.7) at weeks 24, 52, and 104, respectively. The proportions of women with clinically meaningful improvement in the EHP-30 pain domain were 75.9%, 83.6%, and 88.6% at weeks 24, 52, and 104, respectively. Non-pain EHP-30 domain and total scores likewise improved. A positive correlation between changes in dysmenorrhea/NMPP and all EHP-30 domain scores was observed. Results were similar for the delayed relugolix CT and placebo → relugolix CT groups. Sustained reduction of endometriosis-associated pain with relugolix CT observed up to 104 weeks was accompanied by improvements in functioning and health-related QoL. These findings complement the results of the pivotal SPIRIT trials, which showed that relugolix combination therapy significantly reduced dysmenorrhea, NMPP, and dyspareunia vs. placebo in premenopausal women with endometriosis-associated pain. Registration/clinicaltrials.gov identifier: SPIRIT Extension Study (NCT03654274).

A RANDOMIZED CONTROLLED TRIAL OF AUTOLOGOUS TENOCYTE INJECTION VERSUS CORTICOSTEROID INJECTION FOR SYMPTOMATIC PARTIAL THICKNESS ROTATOR CUFF TEARS

BACKGROUND Symptomatic supraspinatus tears are difficult to treat, causing persistent subacromial impingement symptoms. Clinical studies of Autologous Tenocyte Injection (ATI) have shown that cultured tenocytes can synthesize extracellular matrix and facilitate healing of damaged tendon tissue. This randomized controlled trial (RCT) investigated the efficacy of ATI compared to corticosteroid injection (CS), combined with a graded rehabilitation program, in patients with symptomatic tendinopathy and partial thickness cuff tears. METHODS Eligible participants with a duration of symptoms &amp;gt;6 months were recruited and randomized to receive ATI to the interstitial tear or CS to the subacromial bursa in a 2:1 ratio, under ultrasound guidance, followed by a rehabilitation protocol. Assessments were undertaken pre-treatment and at 1, 3, 6 and 12 months post-treatment, including the Constant Score, Visual Analogue Pain Scale (VAS) and American Shoulder and Elbow Surgeons Assessment (ASES). Magnetic resonance imaging (MRI) was performed at baseline, 6 and 12 months. RESULTS Thirty participants were enrolled (ATI=19, CS=11). The ATI group performed significantly better in the Constant Score at 1 (p=0.020, ATI=81.8, CS=67.6), 6 (p=0.026, ATI=84.9, CS=71.1) and 12 (p=0.024, ATI=86.5, CS=65.4) months, reported better (p&amp;lt;0.05) VAS scores at all post-treatment timepoints and reported better ASES scores at all timepoints including 6 (p=0.012, ATI=88.6, CS=74.0) and 12 (p&amp;lt;0.01, ATI=93.3, CS=62.9) months. A total of 7 of 11 CS participants withdrew from the trial between 6 and 12 months due to worsening pain. These patients were subsequently offered and underwent ATI, with 6 and 12 month improvements similar to the primary ATI group. CONCLUSION ATI resulted in a significantly better and sustained reduction in pain, and improvement in shoulder function, compared with CS. This is the first Level 1 study using ATI to treat supraspinatus tears.

Comparing Apotel and Remifentanil for Multimodal Patient-Controlled Analgesia in Postoperative Pain Management Following Total Knee Arthroplasty Surgery: A Randomized Controlled Trial.

Total knee arthroplasty (TKA) is a standard surgical procedure for individuals with debilitating knee arthritis. Effective postoperative pain management is essential for successful recovery, although traditional opioid-based methods have limitations. This study aimed to compare the efficacy of Apotel and remifentanil patient-controlled analgesia in managing postoperative pain after TKA. This double-blind, randomized, controlled clinical trial took place at Amir-al-Momenin and Qods Hospitals in Arak, Iran, spanning from June 2022 to September 2023. Sixty-two eligible patients scheduled for knee joint replacement were randomly assigned to receive either Apotel (Group A) or remifentanil (Group R) as part of multimodal analgesia administered via a pain pump for postoperative pain relief in TKA. The study assessed hemodynamic parameters, pain levels (measured using the Visual Analog Scale), analgesic duration, and narcotic consumption. Statistical analyses were performed using SPSS v.27 and Plotly. Subjects exhibited no statistically significant differences in age, gender distribution, duration of surgery, or anesthesia. The hemodynamic status assessment in the recovery room showed no significant differences in SPO2, PR, or MAP between the groups. However, remifentanil demonstrated superior effectiveness in reducing pain over 24 hours post TKA surgery compared to Apotel, as evidenced by lower average Visual Analog Scale (VAS) scores (P < 0.001), longer duration without the need for narcotic painkillers (P < 0.001), and lower cumulative opioid analgesic consumption in Group R (P < 0.001). Remifentanil demonstrates superior pain control in a multimodal pain management approach compared to Apotel, providing sustained pain reduction over 24 hours post-surgery. Moreover, remifentanil offers longer-lasting pain relief and results in lower cumulative narcotic painkiller consumption compared to Apotel.

Comparing the efficacy of intravenous morphine versus ibuprofen or the combination of ibuprofen and acetaminophen in patients with closed limb fractures: a randomized clinical trial

IntroductionThis study aims to investigate the effectiveness of intravenous ibuprofen or intravenous ibuprofen plus acetaminophen compared to intravenous morphine in patients with closed extremity fractures.MethodsA triple-blinded randomized clinical trial was conducted at a tertiary trauma center in Iran. Adult patients between 15 and 60 years old with closed, isolated limb fractures and a pain intensity of at least 6/10 on the visual analog scale (VAS) were eligible. Patients with specific conditions or contraindications were not included. Participants were randomly assigned to receive intravenous ibuprofen, intravenous ibuprofen plus acetaminophen, or intravenous morphine. Pain scores were assessed using the visual analog scale at baseline and 5, 15, 30, and 60 min after drug administration. The primary outcome measure was the pain score reduction after one hour.ResultsOut of 388 trauma patients screened, 158 were included in the analysis. There were no significant differences in age or sex distribution among the three groups. The pain scores decreased significantly in all groups after 5 min, with the morphine group showing the lowest pain score at 15 min. The maximum effect of ibuprofen was observed after 30 min, while the ibuprofen-acetaminophen combination maintained its effect after 60 min. One hour after injection, pain score reduction in the ibuprofen-acetaminophen group was significantly more than in the other two groups, and pain score reduction in the ibuprofen group was significantly more than in the morphine group.ConclusionThe study findings suggest that ibuprofen and its combination with acetaminophen have similar or better analgesic effects compared to morphine in patients with closed extremity fractures. Although morphine initially provided the greatest pain relief, its effect diminished over time. In contrast, ibuprofen and the ibuprofen-acetaminophen combination maintained their analgesic effects for a longer duration. The combination therapy demonstrated the most sustained pain reduction. The study highlights the potential of non-opioid analgesics in fracture pain management and emphasizes the importance of initiation of these medications as first line analgesic for patients with fractures. These findings support the growing trend of exploring non-opioid analgesics in pain management.Trial registrationClinicalTrials.gov Identifier: NCT05630222 (Tue, Nov 29, 2022). The manuscript adheres to CONSORT guidelines.

Repeat Gamma Knife radiosurgery for recurrent trigeminal neuralgia in patients with multiple sclerosis: a single-center retrospective study.

Gamma Knife radiosurgery (GKRS) has emerged as an effective treatment option for trigeminal neuralgia (TN) in patients with multiple sclerosis (MS). To date, the outcomes of repeat GKRS for patients with TN and MS with recurrent pain have been investigated in a few patients. This study aims to report the outcomes and predictive factors of pain reduction for MS patients undergoing repeat GKRS for recurrent TN. Eighteen patients with MS underwent repeat GKRS for recurrent TN. A retrospective chart review and telephone interviews were conducted to determine background medical history, dosimetric data, and outcomes of the procedure. Facial pain and sensory function were evaluated using the Barrow Neurological Institute (BNI) scales. Fifteen patients achieved a BNI pain score of IIIa or better, indicating pain reduction, within a median period of 21 days after repeat GKRS. The maximum dose for repeat GKRS ranged from 70 to 85 Gy. Pain recurred in 5 patients after a median period of 12 months after GKRS. Percentages of patients with pain reduction at 1, 2, 3, 5, and 7 years were 60%, 60%, 50%, 50%, and 50%, respectively. Older age at repeat GKRS predicted sustained pain reduction (P = 0.01). Seven patients developed facial sensory disturbances, which were bothersome in two patients. Repeat GKRS may be used as an effective treatment modality for prolonging the duration of pain reduction time in patients with MS and TN. After repeat GKRS, facial sensory disturbances are common; however, they are often not bothersome.

Analgesic efficacy and safety of percutaneous thermal ablation plus cementoplasty for painful bone metastases: a systematic review and meta-analysis.

To conduct a systematic review and meta-analysis of publications to evaluate the analgesic efficacy and safety of percutaneous thermal ablation (PTA) plus percutaneous cementoplasty (PCP) (PTA + PCP) for painful bone metastases. We searched PubMed, Cochrane Library and Embase for articles published up to October 2022. Outcomes were a 10-point pain scale, morphine equivalents daily dose (MEDD) and complications. A subgroup confined to spinal bone metastases was analyzed. Twenty-one articles were selected for the analysis. The 21 selected articles involved a total of 661 cases. The pooled pain scales at pre-PTA + PCP, 1day, 1week and 1-, 3-, and 6months post-PTA + PCP were 7.60 (95% confidence interval [CI], 7.26-7.95, I2 = 89%), 3.30 (95% CI, 2.25-4.82, I2 = 98%), 2.58 (95% CI, 1.99-3.35, I2 = 94%), 2.02 (95% CI, 1.50-2.71, I2 = 93%), 1.78 (95% CI, 1.26-2.53, I2 = 95%), and 1.62 (95% CI, 1.14-2.31, I2 = 88%), and in the subgroup, 7.97 (95% CI, 7.45-8.52, I2 = 86%), 3.01 (95% CI, 1.43-6.33, I2 = 98%), 2.95 (95% CI, 1.93-4.51, I2 = 95%), 2.34 (95% CI, 1.82-3.01, I2 = 68%), 2.18 (95% CI, 1.57-3.03, I2 = 78%), and 2.01 (95% CI, 1.16-3.48, I2 = 86%). Mean MEDD decreased up to 3months post-PTA + PCP in 4 articles. The overall pooled major complication rate was 4% (95% CI, 2-6%, I2 = 2%). The updated systematic review and meta-analysis indicates that PTA + PCP for painful bone metastases is safe, and can lead to rapid and sustained pain reduction.

Topical treatment of chemotherapy-induced peripheral neuropathy (CIPN) with high-concentration (179 mg) capsaicin patch in breast cancer patients - results of the QUCIP study.

Chemotherapy-induced peripheral neuropathy (CIPN) following oral or intravenous chemotherapy often results in neuropathic pain, accompanied by symptoms such tingling, burning and hypersensitivity to stimuli, with a notable decline in quality of life (QoL). Effective therapies for CIPN are lacking, with a high demand for analgesics to address this issue. The QUCIP study aimed to assess the effectiveness of high concentration (179 mg) capsaicin patch (HCCP) in alleviating neuropathic pain and associated symptoms in breast cancer patients with confirmed CIPN. QUCIP is a prospective, multi-center observational study spanning 36 weeks with up to three HCCP treatments. Initial treatment (visit V0) was followed by two telephone contacts (T1, T2) and subsequent face-to-face visits every 12 weeks or upon retreatment (visits V1-V3). 73 female patients with painful CIPN post neoadjuvant/adjuvant breast cancer therapy were enrolled. Primary endpoint was the reduction of neuropathic pain symptom score (painDETECT®). Secondary endpoints included improvements in CIPN-specific QoL (QLQ-CIPN20), reductions in pain intensity (numeric pain rating scale, NPRS), and achievement of ≥ 30% and ≥ 50% pain reduction. Median age was 61 years, with 52.0% of patients experiencing peripheral neuropathic pain for > 1 year (> 2 years: 34.2%). The painDETECT® score significantly decreased from baseline (19.71 ± 4.69) to 15.80 ± 6.20 after initial treatment (p < 0.0001) and continued to decrease at follow-up visits. The NPRS indicated significant pain intensity reduction at each time point, particularly pronounced in patients receiving three HCCP treatments. Clinically significant pain relief of ≥ 30% increased from 25.0% at week 4 (T2) to 36.2%, 43.5%, and 40.0% at weeks 12 (V1), 24 (V2), and 36 (V3), respectively. The percentage of patients achieving pain relief of ≥ 50% increased from 14.7% at T2 to 15.5%, 21.7% and 32.5% at V1, V2 and V3, respectively. Patients further reported a significant improvement in their CIPN-related QoL throughout the study. Adverse drug reactions (ADRs) mainly included application site reactions. In this study, HCCP shows benefit in managing CIPN in real-world settings. The data demonstrate a sustained and progressive reduction in neuropathic pain and symptomatology, confirming the clinical benefit of repeated treatment observed in former clinical trials. HCCP treatment has also the potential to significantly improve the QoL associated with CIPN. The safety profile of HCCP was confirmed, supporting its use in clinical practice.

Improvement of Pain Symptoms in Musculoskeletal Diseases After Multimodal Spa Therapy in the Austrian Gastein Valley-A Study Based on Longitudinal Registry Data.

Objective: The study aim was to investigate the course of pain in rest and motion in seven different rheumatic diseases (RMD), prior and after multimodal spa therapy including low-dose radon treatment and at 3-, 6-; and 9-month follow up. Methods: Complete data from the radon indication registry including information on 561 subjects with RMD were analysed to explore the association of timepoint of measurement with pain in rest and motion. For this purpose, linear regression models adjusted for RMD-type, age, sex and body mass index (BMI) were applied. Results: The mean age of the sample was 55years, the average body mass index was 26.8, and 275 subjects were women. Pain scores were significantly improved at all-time points compared to baseline. Pain courses were different for each RMD with the largest improvement seen in fibromyalgia. Conclusion: Timing spa facility visits according to RMD-specific pain courses may result in sustained pain reduction.

Successful Treatment of a Painful Neuroma Using Fascicular Shifting in the Ulnar Nerve: A Case Report

Abstract Objective We report the case of a 40-year-old man with an inveterate ulnar nerve neuroma following a laceration injury of his left wrist twenty-three years ago. The patient presented with a typical ulnar claw-hand deformity and debilitating neuropathic pain in his hand (VAS 8.4). Pre-operative imaging revealed a neuroma of the ulnar nerve at the Guyon's canal. Moreover, a complete atrophy of all intrinsic hand muscles innervated by the ulnar nerve was present. Methods A Zancolli lasso procedure was performed to reduce the clawing effect. The neuroma was resected producing a nerve defect of five centimeters. Since the injury dated back more than two decades and any motor recovery was deemed impossible at that point, the motor fascicle of the ulnar nerve, i.e. the deep branch, was selectively neurolysed and harvested as an autologous nerve graft. Then the graft was shifted into the defect to be coapted with the superficial branch fascicle in an end-to-end fashion. Results The presented fascicular shift procedure resulted in satisfying and sustained pain reduction. At the six-month follow-up, the VAS decreased to 1.2, and two years post-operatively, the patient reported 2.5 on the VAS. Conclusion The fascicular shift procedure offers an alternative approach to conventional nerve grafts. If nerve grafting is required, using a locally harvested graft avoids additional donor site morbidity. Assuming the clinical scenario allows for fascicular grafting, we strongly suggest considering the fascicular shift procedure as a cost-effective alternative to expensive conduits and processed nerve allografts in sensory nerve reconstruction.

Feasibility and acceptability of perioperative application of biofeedback-based virtual reality versus active control for pain and anxiety in children and adolescents undergoing surgery: protocol for a pilot randomised controlled trial

IntroductionCurrent clinical applications of virtual reality (VR) provide patients with transient pain relief during acutely painful events by redirecting attention. Biofeedback (BF) is a mind–body therapy that effectively produces sustained...

Long-Term Clinical Outcomes of a Remote Digital Musculoskeletal Program: An Ad Hoc Analysis from a Longitudinal Study with a Non-Participant Comparison Group.

Digital solutions have emerged as an alternative to conventional physiotherapy, particularly for chronic musculoskeletal pain (CMP) management; however, its long-term effects remain largely unexplored. This study focuses on patients reporting CMP, assessing 1-year clinical outcomes after a multimodal digital care program (DCP) versus non-participants, who enrolled in the program but never engaged in a single exercise session or partook of the educational content made available to them. In this longitudinal study ad-hoc analysis, pain and functionality outcomes at 1-year reassessment were studied, focusing on the odds of reaching minimal clinically important difference (MCID) and, overall average reduction in both outcomes. Healthcare utilization was additionally studied within the same period. From 867 individuals allocated to the study, 460 completed the 1-year reassessment (intervention group: 310; comparison group: 150). The intervention group presented sustained and greater pain reduction until 1-year reassessment than the comparison group, reflecting greater odds ratio of achieving the MCID both in pain and functionality (1.90 95% CI: 1.27-2.86, p = 0.002 and 2.02 95% CI: 1.31-3.12, p = 0.001, respectively). A lower healthcare utilization during the 1-year follow-up was observed in the intervention group than in the comparison group. This study suggests that a digital CMP program may have a lasting impact on improved pain and functionality in patients with CMP.

EGFR Signaling Is Overactive in Pachyonychia Congenita: Effective Treatment with Oral Erlotinib

Pachyonychia congenita (PC) is a rare keratinizing disorder characterized by painful palmoplantar keratoderma for which there is no standard current treatment. PC is caused by dominant mutations in keratin (K) K6A, K6B, K6C, K16, or K17 genes involved in stress, wound healing, and epidermal barrier formation. Mechanisms leading to pain and painful palmoplantar keratoderma in PC remain elusive. In this study, we show overexpression of EGFR ligands epiregulin and TGF-α as well as HER1‒EGFR and HER2 in the upper spinous layers of PC lesions. EGFR activation was confirmed by upregulated MAPK/ERK and mTOR signaling. Abnormal late terminal keratinization was associated with elevated TGM1 activity. In addition, the calcium ion permeable channel TRPV3 was significantly increased in PC-lesional skin, suggesting a predominant role of the TRPV3/EGFR signaling complex in PC. We hypothesized that this complex contributes to promoting TGM1 activity and induces the expression and shedding of EGFR ligands. To counteract this biological cascade, we treated three patients with PC with oral erlotinib for 6‒8 months. The treatment was well-tolerated and led to an early, drastic, and sustained reduction of neuropathic pain with a major improvement of QOL. Our study provides evidence that targeted pharmacological inhibition of EGFR is an effective strategy in PC.

Long-term Clinical Outcomes Following Endoscopic Foraminoplasty for Patients With Single-Level Foraminal Stenosis of the Lumbar Spine.

The aim of this study is to evaluate the safety and long-term clinical outcomes of transforaminal endoscopic foraminoplasty using local anesthesia and total intravenous analgesia (TIVA) in patients with single-level lumbar foraminal stenosis and unilateral leg pain. Postoperative pain relief was self-evaluated by 46 consecutive patients using a visual analog scale (VAS) and Oswestry Disability Index (ODI). Patient scores were obtained before the procedure and at 6, 12, 24, and 60 months after surgery. Pain reduction of at least 50% in the VAS score and a decrease of at least 50% or more in ODI score was achieved in 37 of 46 patients throughout the follow-up period. Median VAS score decreased from 7.5 preoperatively to 2.5 postoperatively. Median ODI score decreased from 62% preoperatively to 15% postoperatively. All patients reached 24-month follow-up and 37 patients reached 60-month follow-up. There were no surgery-related complications. Transforaminal endoscopic foraminoplasty performed under local anesthesia and TIVA produces sustained reduction in pain and improves functionality in patients with single-level lumbar foraminal stenosis without complications even in patients with comorbidities. Endoscopic foraminoplasty may be a useful adjunct to open micro decompressive surgery for patients with foraminal stenosis of the lumbar spine LEVEL OF EVIDENCE: 4.

Genicular artery embolization as a novel treatment for mild to moderate knee osteoarthritis: protocol design of a randomized sham-controlled clinical trial

IntroductionKnee osteoarthritis is a common disease with pain as the most prevalent symptom. Previous cohort studies have shown genicular artery embolization to reduce pain symptoms in patients with mild to moderate knee osteoarthritis. Patients resistant to conservative therapy but not eligible yet for surgical treatment due to young age or comorbidities may profit from an effective and sustained pain reduction treatment. This study is a randomized sham-controlled trial to evaluate the efficacy of genicular artery embolization in patients with knee osteoarthritis.Methods and analysisFifty-eight patients with mild-to-moderate knee osteoarthritis will be recruited and randomly allocated to the treatment or control group in a 1:1 ratio. Participants in the treatment group will undergo genicular artery embolization. Patients in the control group will undergo sham treatment. Outcome measurements will be assessed at baseline and after 1, 4, 8, and 12 months with questionnaires, pressure pain threshold testing, and MR imaging. The MR imaging protocol is designed to (semi)quantitatively assess osteoarthritis in the knee joint. The primary outcome is the change from baseline of the Knee injury and Osteoarthritis Outcome Score (KOOS) pain subscale after 4 months. Secondary outcomes include change in osteoarthritis-related questionnaires, pressure pain threshold, and OA-related MRI features, particularly synovitis and bone marrow lesions.Ethics and disseminationThis trial will determine the efficacy of genicular artery embolization compared to a sham treatment. This is of importance to assess before proceeding to larger-scale efficiency studies and, ultimately, implementing this treatment into day to day clinical practice.Trial registrationClinicalTrials.gov NCT03884049. Registered on 21 March 2019

Analgesic efficacy of remifentanil patient-controlled analgesia versus combined spinal-epidural technique in multiparous women during labour

To compare the analgesic profile of remifentanil patient-controlled analgesia (RPCA) and combined spinal-epidural analgesia technique (CSEA) in multiparous women during the entire labour. We hypothesized that CSEA would provide a better and more sustained pain reduction than RPCA. A prospective observational trial under ID NCT02963337 at a university hospital in Slovenia 2017-2018. Analgesic efficacy, satisfaction with pain-relief, adverse effects, labour progress, and outcomes between RPCA (80) and CSEA (81) were compared. CSEA provided significantly lower pain scores during the entire labour. Compared to baseline, significant pain reduction was recorded in both groups after 15 min. No difference was recorded compared to baseline with RPCA and CSEA after 45 and 90 mins, respectively. CSEA provided higher satisfaction than RPCA (5 [5-5] vs 5 [4-5], p < 0.0001). More patients with CSEA opted for the same technique for the next labour [CSEA; 77 (95%) vs RPCA; 65 (81%), p = 0.003]. No crossovers were observed. RPCA was associated with desaturation (34%), bradypnea (21%) and apnoea (25%), which were transitional and easily managed. None had severe sedation. No differences were recorded in labour progress and outcomes. Apgar scores were reassuring in all neonates (> 8). None had umbilical artery pH < 7.0. In multiparas, CSEA provided superior analgesia and satisfaction than RPCA. Nevertheless, RPCA provided a satisfactory experience, suggesting it could be used when neuraxial analgesia is not available, preferred, or contraindicated. In that case, constant presence of midwife is mandatory for management of clinically significant hypoventilation.

Five-Year Outcomes After Transforaminal Endoscopic Foraminotomy and Discectomy for Soft and Calcified Thoracic Disc Herniations.

The aim of this study was to evaluate the safety and long-term clinical outcomes of transforaminal full endoscopic discectomy and foraminotomy performed with manual reamers under local anesthesia on soft and calcified herniated discs in the mid and lower thoracic spine. Postoperative pain relief was self-evaluated by 16 patients using a visual analog scale (VAS) and Oswestry Disability Index (ODI). Patients were scored at 6, 12, 24, and 60 months after surgery. Significant pain reduction of more than 50% in the VAS score was achieved in 15 out of 16 patients at all review points throughout this study. Similarly, a decrease of more than 50% in ODI scores was achieved in 15 out of 16 patients in all 4 review points. There were no surgical complications. Good postoperative results were achieved in patients regardless of the consistency of the disc herniation. Transforaminal full endoscopic discectomy and foraminotomy with manual reamers performed under local anesthesia produces sustained reduction in pain and improves functionality in patients with mid and lower thoracic spine soft and calcified disc herniations. The surgery is safe and straightforward to perform with the correct training. 4. Thoracic transforaminal endoscopic discectomy and foraminotomy, performed in TIVA, may be a useful adjunct for treatment of patients with soft and calcified disc herniations in thoracic spine.