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

Introduction Knee 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 analysis Fifty-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 dissemination This 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 registration ClinicalTrials.gov NCT03884049. Registered on 21 March 2019

Immediate Effects of Spinal Manipulation on Painful Sensitivity and Postural Stability in Patients with Chronic Nonspecific Low Back Pain: Study Protocol for A Controlled Randomised Clinical Trial.

Background: Low back pain is one of the main public health concerns. Chronic low back pain (cLBP)reduces functional capacity and affects postural stability.Although health professionals widely use spinal manipulation, its immediate effect on painful sensitivity and postural stability is lacking. This study aims to verify the immediate effects of lumbar spinal manipulation on the pressure pain threshold and postural stability in individuals with cLBP. Methods: A two-arm, placebo-controlled clinical trial with parallel groups and examiner-blinded will be conducted with 80 participants with cLBPfrom an outpatient physical therapy department,randomly allocated at a 1:1 distribution. The experimental group will receive a lumbar spinal manipulation technique, and the placebo group will receive a simulated lumbar spinal manipulation. Both groups will receive one session of treatment and will be evaluated before and immediately after the intervention.The primary outcomes will be the pressure pain threshold and postural stability. Pain intensity and patient´s expectation will be assessed as a secondary outcome. The pressure pain threshold will be assessed using a pressure algometer in 6 different anatomical regions. The evaluation of postural stability will be performed in a baropodometry exam by displacing the centre of pressure. The pain intensity will be measuredusing the Numeric Pain Rating Scale. A Likert scale will be used for the patient´s expectationabout the treatment. A two-way analysis of variance will compare the effect of the interventions between groups. Discussion:This study will provide insights regarding the immediate effects of spinal manipulation in patients with cLBPagainst a simulated spinal manipulation using objective outcomes and considering patients’ expectations regarding the treatment.Trial registration: Brazilian Registry of Clinical Trials:RBR-3ksq2c; registered on 13 July 2020.

Efficacy of open-label counterconditioning for reducing nocebo effects on pressure pain

Nocebo effects can adversely affect the experience of physical symptoms, such as pain and itch. Nocebo effects on itch and pain have shown to be induced by conditioning with thermal heat stimuli and reduced by counterconditioning. However, open-label counterconditioning, in which participants are informed about the placebo content of the treatment, has not been investigated, while this can be highly relevant for clinical practice. Furthermore, (open-label) conditioning and counterconditioning has not been investigated for pain modalities relevant to musculoskeletal disorders, such as pressure pain. In a randomized controlled trial, we investigated in 110 healthy female participants whether nocebo effects on pressure pain combined with open-label verbal suggestions can be 1) induced via conditioning and 2) reduced via counterconditioning. Participants were allocated to either a nocebo or sham conditioning group. Next, the nocebo group was allocated to either counterconditioning, extinction, or continued nocebo conditioning; sham conditioning was followed by placebo conditioning. Nocebo effects were significantly larger after nocebo conditioning than sham conditioning (d = 1.27). Subsequently, a larger reduction of the nocebo effect was found after counterconditioning than after extinction (d = .99) and continued nocebo conditioning (d = 1.63), with effects similar to placebo conditioning (following sham conditioning). These results show that (counter)conditioning combined with open-label suggestions can modulate nocebo effects on pressure pain, which provides promise in designing learning-based treatments to reduce nocebo effects in patients with chronic pain disorders, particularly for musculoskeletal disorders.

The impact of gender of the examiner on orofacial pain perception and pain reporting among healthy volunteers

Objectives Pain on palpation of jaw muscles is a commonly used diagnostic criterion when examining patients with orofacial pain. It is not known, however, if pain reports are affected by the gender of the examiner. Our aim was to investigate if pressure pain threshold (PPT), pressure pain tolerance (PTol), and pain intensity assessed over the masseter muscles in healthy individuals are affected by the gender of the examiner. Materials and methods Healthy, pain-free individuals were recruited on a voluntary basis. PPT and PTol were assessed using pressure algometry. At the PTol level, participants also rated pain intensity on a 0–10 numeric rating scale. Assessments of PPT and PTol were conducted with six repeated measurements performed twice, separately by one female and one male examiner, on each participant. Results In total, 84 participants (43 women; median age 24, IQR 6) were included. With a female examiner, women reported higher pain intensity than men (Mann Whitney U, p = 0.005). In the multivariable analysis, significantly higher PTol was predicted by male examiner. Also, a higher ratio between PTol and reported pain intensity was predicted by male examiner. Conclusions The gender of the examiner influences pain reporting and perception in an experimental setting. This effect on pain perception related to gender of the examiner is probably related to normative gender behaviors rather than to biological alterations within the examined individual. Clinical relevance In clinical and experimental settings, gender of the examiner may affect not only pain perception but also pain reporting, with potential implications for diagnostics in patients with pain.

The importance of the local twitch response during needling interventions in spinal pain associated with myofascial trigger points: a systematic review and meta-analysis

Objective: To compare the clinical effects of needling interventions eliciting local twitch responses (LTRs) versus needling without eliciting LTRs when applied to muscle trigger points (TrPs) associated with spinal pain of musculoskeletal origin. Databases and data treatment: Electronic databases were searched for randomized or non-randomized clinical trials where one group received needling intervention where LTRs were elicited and was compared with another group receiving the same intervention without elicitation of LTRs in spinal pain disorders associated with TrPs. Outcomes included pain intensity, pain-related disability, and pressure pain thresholds. The risk of bias (RoB) was assessed using the Cochrane risk of bias tool or ROBINS-I tool, methodological quality was assessed with the PEDro score, and quality of evidence was evaluated using the GRADE approach. Results: Six trials were included. The application of a needling intervention eliciting LTRs was associated with a significant reduction in pain intensity immediately after treatment (mean difference (MD): −2.03 points, 95% confidence interval (CI): −3.77 to −0.29; standardized MD (SMD): −1.35, 95% CI: −2.32 to −0.38, p = 0.02) when compared to the same needling intervention without elicitation of LTRs. No effect at short-term follow-up (MD: −0.20 points, 95% CI: −1.46 to 1.06, p = 0.75) was observed. No significant differences based on elicitation or non-elicitation of LTRs were found in related disability (SMD: −0.05, 95% CI: −0.41 to 0.30, p = 0.77) or pressure pain thresholds (MD: 23.39 kPa, 95% CI: −13.68 to 60.47, p = 0.22). Discussion: Low-level evidence suggests an immediate effect of obtaining LTRs during needling interventions on pain intensity, with no significant effects on related disability or pressure pain sensitivity in spinal pain disorders associated with muscle TrPs. Registration number: OSF Registry— https://doi.org/10.17605/OSF.IO/5ZX9N

Active Virtual Reality Games Reduce Pain Sensitivity in Young, Healthy Adults

Separately, both physical activity and virtual reality can attenuate pain sensitivity in healthy adults. What is unknown is whether virtual reality combined with physical activity (active virtual reality) could have a greater hypoalgesic effect compared to non-active virtual reality distraction (passive virtual reality engagement).Objective: The purpose of this study was to determine whether playing physically active virtual reality games exert a greater hypoalgesic effect than a non-active virtual reality game.Methods: Participants (n = 36) played three different active virtual reality games (Beat Saber, Holopoint, and Hot Squat) and one non-active virtual reality game (Relax Walk) for 15 min on four different visits. During gameplay, participants wore accelerometers on the thigh, wrist, and waist to measure movement intensity and quantity. Pressure pain thresholds were measured on the forearm and thigh immediately prior to gameplay (pretest) and immediately following each gaming bout (posttest).Results: Analysis of the accelerometer data indicated that Hot Squat elicited greater whole-body and lower body moderate to vigorous physical activity compared to the other games. The ANOVA revealed an overall hypoalgesic effect of the virtual reality games on the forearm, regardless of game type. Results also showed a significant hypoalgesic effect on the thigh following gameplay for Hot Squat, Holopoint, and Relax Walk VR. The magnitude of pain reduction was significantly greater during Hot Squat compared to the other games.Conclusion: Virtual reality gameplay exerted a hypoalgesic effect on experimental pressure pain. Additionally, the data provided evidence of a potential enhanced hypoalgesic effect of physically active virtual reality compared to non-active VR on pressure pain sensitivity.

Pain thresholds and suprathreshold pain after sleep restriction in migraine – A blinded crossover study

Objective There is an unexplained association between disturbed sleep and migraine. In this blinded crossover study, we investigate if experimental sleep restriction has a different effect on pain thresholds and suprathreshold pain in interictal migraineurs and controls. Methods Forearm heat pain thresholds and tolerance thresholds, and trapezius pressure pain thresholds and suprathreshold pain were measured in 39 interictal migraineurs and 31 healthy controls after two consecutive nights of partial sleep restriction and after habitual sleep. Results The effect of sleep restriction was not significantly different between interictal migraineurs and controls in the primary analyses. Pressure pain thresholds tended to be lower (i.e., increased pain sensitivity) after sleep restriction in interictal migraineurs compared to controls with a 48-hour preictal-interictal cut-off (p = 0.061). We found decreased pain thresholds after sleep restriction in two of seven migraine subgroup comparisons: heat pain thresholds decreased in migraineurs with lower pain intensity during attacks (p = 0.005) and pressure pain thresholds decreased in migraineurs with higher severity of photophobia during attacks (p = 0.031). Heat pain thresholds tended to decrease after sleep restriction in sleep-related migraine (p = 0.060). Sleep restriction did not affect suprathreshold pain measurements in either group. Conclusion This study could not provide strong evidence for an increased effect of sleep restriction on pain sensitivity in migraineurs compared to healthy controls. There might be a slightly increased effect of sleep restriction in migraineurs, detectable using large samples or more pronounced in certain migraine subgroups.