Rejected

Araçá-verdadeiro is the popular name of (Myrtaceae), whose fruits and leaves are used in Brazilian folk medicine for treatment of inflammation and pain. The focus of the present research was an investigation of the anti-nociceptive, and anti-inflammatory effects of the essential oil from (EOPG) leaves, and of spathulenol. The anxiolytic and antidepressive effects associated with chronic pain were also investigated in models of acute or persistent nociception or/and inflammatory pain. Oral treatment with EOPG (10-100 mg/kg) or spathulenol (10 mg/kg) significantly inhibited formalin-induced nociceptive responses, both sensitivity to cold and edema. Oral treatment with EOPG (10 mg/kg) and spathulenol (10 mg/kg) did not reduce locomotor activity (open field test). Local administration of spathulenol (1000 µg/paw) significantly prevented formalin-induced nociceptive sensitivity to cold and paw edema, and carrageenan-induced mechanical hyperalgesia, paw edema and sensitivity to cold. In the Freund's complete adjuvant (CFA) model, oral treatment with EOPG (10 mg/kg) or spathulenol (10 mg/kg) for 21 days significantly inhibited all analyzed parameters. The percentage maximal inhibition by spathulenol was 76.00% (mechanical hyperalgesia), 71.90% (cold response), 85.00% (edema), 77.16% (myeloperoxidase activity), 97.72% (time in the closed arms in the elevated plus maze), and 49.00% (immobility time in the tail suspension test), in the CFA model. Models employed male mice, except for the CFA test, which employed C57bL6 male mice (=6 /group). This study demonstrates that EOPG is an anti-nociceptive and anti-hyperalgesic agent, in acute and continuous treatment, and an anxiolytic and antidepressive agent when tested with the chronic pain experimental state.

BACKGROUND The aim of this study was to assess inflammatory cytokines levels in synovial fluid (SF) before and after electroacupuncture (EA) treatment and to explore whether these biomarkers are associated with function of rotator cuff tear (RCT) patients. MATERIAL AND METHODS We recruited 54 patients with RCT and separated them into an EA group and a control group. The SF biomarker levels were detected at baseline and at 6-week and 6-month follow-up. The symptomatic severity was evaluated by visual analog scale (VAS), Constant-Murley score, and American Shoulder and Elbow Surgeons score (ASES). We also investigated the correlation between symptomatic severity and biomarker levels in SF of the shoulder joint. RESULTS The reductions in VAS and improved functional score (ASES and Constant-Murley score) were significantly different between the 2 groups, and SF biomarker concentrations were significantly lower in the EA group. IL-1ß levels were significantly negatively correlated with Constant-Murley score (r=-0.73, P=0.04) and ASES score (r=-0.59, P<0.001) and positively correlated with VAS scores (r=0.81, P=0.004). IL-6 levels were significantly negatively correlated with Constant-Murley score (r=-0.67, P=0.03) and positively correlated with VAS score (r=0.7, P=0.01). MMP-1 levels were significantly negatively correlated with ASES score (r=-0.57, P<0.001). CONCLUSIONS The biomarkers in SF were directly associated with shoulder pain and shoulder function in rotator cuff tear. EA, as a safe and effective conservative therapy, obviously decreased the level of inflammatory cytokines in RCT patients, accompanied by a reduction in shoulder pain and improved function.

To describe the prevalence, location and impact of moderate to severe pain experienced on most days in community-dwelling older (≥70 years) adults who were ASPirin in Reducing Events in the Elderly (ASPREE) clinical trial participants. Cross-sectional ASPREE Longitudinal Study of Older Persons (ALSOP) data were collected from self-reported questionnaires administered to 16,439 ASPREE participants. Of 14,155 respondents, 41% of males ( = 2651/6475) and 50% of females ( = 3803/7680) reported experiencing pain on most days. One quarter of respondents reported experiencing pain on most days that was moderate or severe in intensity ( = 3560/14,155), commonly located in the lower back, knees and upper back. Of those reporting moderate or severe pain, 51% reported taking analgesic medication on most days ( = 1812/3560), almost one-third also reported regular interference with sleep (29%, = 1024/3560), walking (35%, = 1239/3560) and daily activities (41%, = 1467/3560). Lower back, knee or upper back pain is a common accompaniment of ageing.

The Sedentary Behavior Questionnaire (SBQ) is a brief and easy instrument to measure time spent on sedentary activities; however, no study has investigated the reliability and validity of this questionnaire in people with chronic low back pain (LBP).

Given the importance of the cartilage endplate in low back pain, there is a need to characterize the humancartilage endplateatthe molecular, cell and tissue level in order to inform treatment strategies whichtarget it. The goal of this study was to characterize the structure, matrix composition, and cell phenotype of the human cartilage endplate compared to adjacent tissues within the intervertebral joint: thenucleus pulposus andannulus fibrosus,andarticular cartilage. Isolated cartilage endplate, nucleus pulposus, annulus fibrosus and articular cartilage tissue and cells were evaluated for cell morphology, matrix composition, collagen structure, glycosaminoglycan content, and gene and protein expression. Thecartilage endplate containedelongated cells which mainly produce a collagen rich interterritorial matrix and proteoglycan rich territorial matrix. The cartilage endplate contained significantly less glycosaminoglycans than the nucleus pulposus tissue. Significant differences in matrix and cell markergene expression were observed between cartilage endplate and nucleus pulposusorannulus fibrosus, with greatest differences between cartilage endplate and articular cartilage. We were able to distinguishnucleus pulposus from cartilage endplatecells using collagen-10, highlighting collagen-10 as a potential cartilage endplate marker. Our findings suggest that at the cell and tissue level, thecartilage endplatedemonstrates both similarities and differences when compared with nucleus pulposus, annulus fibrosus and hyaline articular cartilage. This work highlights a unique structure, matrix composition and cell phenotype for the human cartilage endplate and can help inform regenerative strategies that target the intervertebral disc joint in chronic low back pain. This article is protected by copyright. All rights reserved.

There are a number of options for the symptomatic treatment of peripheral neuropathy, but the overall treatment outcomes remain unsatisfactory.

Traumatic brain injury (TBI) is a frequent cause of chronic headache, fatigue, insomnia, hyperactivity, memory deficits, irritability and posttraumatic stress disorder. Recent evidence suggests beneficial effects of pro-cannabinoid treatments. We assessed in mice levels of endocannabinoids in association with the occurrence and persistence of comparable sequelae after controlled cortical impact in mice using a set of long-term behavioral observations in IntelliCages, motor and nociception tests in two sequential cohorts of TBI/sham mice. TBI mice maintained lower body weights, and they had persistent low levels of brain ethanolamide endocannabinoids (eCBs: AEA, OEA, PEA) in perilesional and subcortical ipsilateral brain tissue (6 months), but rapidly recovered motor functions (within days), and average nociceptive responses were within normal limits, albeit with high variability, ranging from loss of thermal sensation to hypersensitivity. TBI mice showed persistent non-goal directed nighttime hyperactivity, i.e. they visited rewarding and non-rewarding operant corners with high frequency and random success. On successful visits, they made more licks than sham mice resulting in net over-licking. The lower the eCBs the stronger was the hyperactivity. In reward-based learning and reversal learning tasks, TBI mice were not inferior to sham mice, but avoidance memory was less stable. Hence, the major late behavioral TBI phenotype was non-goal directed nighttime hyperactivity and "over-licking" in association with low ipsilateral brain eCBs. The behavioral phenotype would agree with a "post-TBI hyperactivity disorder". The association with persistently low eCBs in perilesional and subcortical regions suggests that eCB deficiency contribute to the post-TBI psychopathology.

Up to 50% of patients with symptomatic knee osteoarthritis (OA) present with neuropathic pain (NP) features. We assessed the impact of NP according to DN4 (Douleurs Neuropathiques 4 questions) score on the response to intra-articular (IA) hyaluronic acid (HA) injections and the effects of HA injections on NP.

To assess the comparative efficacy of traditional non-steroidal anti-inflammatory drugs (NSAIDs) and selective cyclo-oxygenase-2 inhibitors in patients with acute gout.

To review the pharmacology, pharmacokinetics, efficacy, safety, and place in therapy of rimegepant for treatment of migraine.