Painful knee osteoarthritis (KOA) is common, pharmacological treatment, however, is often hampered by limited tolerability. Cannabidiol, which preclinically showed anti-inflammatory, analgesic activity, could supplement established analgesics, but robust clinical trials are lacking. The aim of our study was to investigate the effects of oral high-dose CBD administered over 8 weeks on pain, function and patient global assessment as an add-on to continued paracetamol in chronic symptomatic KOA. Prospective, randomized, placebo-controlled, double-blind, parallel-group study. Single center, Outpatient Clinic, Department of Special Anaesthesia and Pain Therapy at Medical University of Vienna, Austria. Eligibility criteria included: age: 18–98 years; painful KOA; score ≥5 on the pain subscale of the Western Ontario and McMasters Universities Osteoarthritis (WOMAC) Index; KOA confirmed by imaging. Participants were on continued dosage of paracetamol 3 g/d and randomly assigned by web-based software 1:1 to oral cannabidiol 600 mg/d (n = 43) or placebo (n = 43). Study period: 8 weeks. Primary outcome: Change in WOMAC pain subscale scores (0 = no pain, 10 = worst possible pain) from baseline to week 8 of treatment. Trial Registration: ClinicalTrials.gov Identifier: NCT04607603. Trial is completed. The trial was conducted from October 1, 2020 to March 29, 2022. 159 patients screened, 86 randomized. Among 86 participants (mean age, 62.8 [SD 20.3] years; 60 females [69.8%]), 58 (67.4%) completed the trial. Mean baseline WOMAC pain subscale was 6.0 ± 1.1. Analysis: Intention-to-treat principal. Mean reduction in WOMAC pain subscale was 2.5 (95% CI: 1.8–3.3) in the cannabidiol group and 2.4 (95% CI: 1.7–3.2) in the placebo group with no significant group difference (p = 0.80). Adverse events were significantly more frequent with cannabidiol (cannabidiol: 135 [56%]; placebo: 105 [44%]) (p = 0.008). Rise above baseline of liver aminotransferases and gamma-glutamyltransferase was significantly more common in the cannabidiol (n = 15) than the placebo group (n = 5) (p = 0.02). In KOA patients, oral high-dose add-on cannabidiol had no additional analgesic effect compared to adding placebo to continued paracetamol. Our results do not support the use of cannabidiol as an analgesic supplement in KOA. Trigal Pharma GmbH.

Background and Objectives: Chronic neck pain and low back pain are common conditions in high-income countries leading to social and medical problems such as invalidity and decreased quality of life. The aim of this study was to investigate the effect of supra-threshold electrotherapy on pain level, subjective feeling of disability, and spinal mobility in patients with chronic pain in the spinal cord. Materials and Methods: 11 men and 24 women with a mean age of 49 years were randomly divided into three groups: group 1, “therapy”: supra-threshold electrotherapy was applied on the whole back after electrical calibration; group 2, “control”: electrical calibration without successive electrotherapy; group 3, “control of control”: no stimulation. Sessions were performed once a week and six times in total, each lasting 30 min. The numeric pain rating scale (NRS), cervical and lumbar range of motion (ROM), as well as disability in daily live were investigated before and after the sessions using questionnaires (Neck Disability Index, Roland Morris Questionnaire, Short-form Mc Gill Pain Questionnaire (SF-MPQ)). Results: Spinal mobility improved significantly in the lumbar anteflexion (baseline mean, 20.34 ± SD 1.46; post session mean, 21.43 ± SD 1.95; p = 0.003) and retroflexion (baseline mean, 13.68 ± SD 1.46; post session mean, 12.05 ± SD 1.37; p = 0.006) in the group receiving electrotherapy. Pain levels measured by the NRS and disability-questionnaire scores did not differ significantly before and after treatment in any of the groups. Conclusions: Our data indicate that regular supra-threshold electrotherapy for six times has a positive effect on lumbar flexibility in chronic neck pain and low back pain patients, whereas pain sensation or subjective feeling of disability remained unchanged.

Background and Objectives: Pain is a multidimensional phenomenon with a wide range regarding the location, intensity and quality. Patients with chronic pain, in particular those suffering from mixed pain, often present a special challenge. The PainDETECT questionnaire (PD-Q) is a screening instrument designed to classify whether a patient has neuropathic pain (NP), often rated as more distressing compared to nociceptive pain. The objective of this study was to investigate whether the PD-Q score correlates with pain intensity, measured with the numeric rating scale (NRS), in chronic pain patients in an outpatient setting. Materials and Methods: A questionnaire-based study was conducted to identify the associations between the unidimensional NRS scale for pain intensity and the PD-Q score for screening of an NP component in an outpatient setting. Participants were asked to fill in the questionnaire themselves. Results: One hundred seventy-six participants completed the PD-Q questionnaire and rated pain on the NRS scale at the baseline visit. The PD-Q and NRS scores significantly correlated at the baseline visit and the 1-month follow-up visit in chronic pain patients. The identification of a neuropathic component in chronic pain may permit more targeted and effective pain management. Conclusions: The findings of our questionnaire suggest that a significant proportion of chronic pain patients had manifested features of NP at the first visit to the outpatient clinic. The PD-Q is a useful screening tool to alert clinicians of NP that may need further diagnostic evaluation or therapeutic intervention and may also help to predict treatment response. Further research is needed to investigate if a correlation is predictive of treatment response when pain therapy targets NP.

Inflammatory pain is a major clinical challenge, yet appropriate human models mimicking local infection are lacking. We established a novel human pain model based on intradermal administration of lipopolysaccharide (LPS), a component of Gram-negative bacteria, and investigated the time course and underlying molecular mechanisms of inflammatory pain hypersensitivity. In a placebo-controlled pilot study with 12 healthy subjects, the intradermal LPS injection induced hyperaemia peaking at 4.5 h and mechanical hypersensitivity peaking at 6 h. Hypersensitivity to increasingly acidic injections and mechanical pinch lasted longer than hyperaemia. The double-blind, randomized, placebo-controlled full crossover main study was completed by 40 subjects and investigated the role of the Receptor for Advanced Glycation End-products (RAGE). Co-injection of the RAGE antagonist azeliragon largely reduced LPS-induced hyperaemia (-87%) and significantly attenuated hypersensitivity to mechanical (-55%) and increasingly acidic stimuli (-40%). In contrast, the Toll-like receptor 4 antagonist resatorvid had no effect on any readout. In both naïve and inflamed skin, TRPV1 antagonist BCTC inhibited the majority of acid-induced pain. LPS-induced inflammation caused a substantial shift in the pH sensitivity of pain, suggesting that even mild tissue acidification contributes to inflammatory pain. The human LPS skin inflammation model is largely RAGE-dependent, highlighting its potential as a target in inflammation.

In Reply Sibylle Pramhas;Regina Schukro;Angelika Geroldinger;Georg Heinze;Hans-Georg Kress; Anesthesiology

Background/Objectives: Before permanent implantation of a Spinal Cord Stimulation (SCS) system for treatment of chronic pain conditions a trial phase is standard, though its utility is increasingly disputed. Comparisons of long-term to trial-phase pain levels are sparse, and whether trial pain scores predict system explantation risk is unclear. We compare long-term and trial-phase pain levels in SCS treatment and investigate association between trial numeric rating scale (NRS) pain score and explantation. Methods: This retrospective, single-centre study analysed patients who underwent SCS implantation with long-term follow-up. Patients were included if baseline and trial NRS diaries were available and trial phase was successful. Missing follow-up NRS values were extracted from patient files, multiple imputation addressing remaining gaps. ROC analysis, log-rank test, logistic regression, and Cox proportional hazards models evaluated association between trial-phase NRS and explantation. Results: 71 patients (49.3% female, mean age 53.1 ± 13.0 SD years) were included. NRS reduction during trial was −3.52 from baseline [95% CI: −2.94, −4.09] (p < 0.0001). NRS reduction from baseline to long-term follow-up was −1.94 [95% CI: −1.1, −2.74] (p < 0.0001). NRS increased by 1.58 [95% CI: 0.78, 2.38] from trial to follow-up (mean follow-up at 4.42 years [95% CI: 3.53, 5.30]) (p < 0.0002). Higher trial NRS was associated with higher odds of explantation. (Odds Ratio: 1.38 per one-point NRS increase (95% CI: 1.01–2.04, p = 0.0458). Conclusions: In SCS there is significant attrition of pain reduction from trial to long-term follow-up. Higher trial NRS showed a possible association with higher odds of explantation. Therefore, pain reduction during trial phase does not necessarily reflect long-term results and utility of trial-phase pain levels for estimation of explantation risk warrants further investigation.