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Context: We designed this study to investigate the effects of 2 myofascial release techniques, Instrument-Assisted Soft Tissue Mobilization (IASTM) and Foam Roller (FR), on pain, joint range of motion, and muscle strength in athletes suffering from iliotibial band (ITB) tightness. Design: A total of 39 male soccer players were enrolled in this randomized controlled trial, aged between 18 and 23 years who were divided into 3 groups: Only Exercise, IASTM, and FR. Methods: All participants performed daily strengthening and stretching exercises, while 1 group added IASTM, and the other added FR to the exercise program. We evaluated ITB tightness with the Ober test and an inclinometer, pressure pain threshold, using an algometer, and we evaluated muscle strength with the Cybex Norm Isokinetic device. Results: We found that all 3 groups exhibited an increase in the Ober inclination angle after the interventions (P =.001), but the increase was greater for participants in the IASTM and FR groups, compared with exercise alone. Additionally, both the IASTM and FR groups displayed an increased pressure pain threshold (P =.001), whereas there was no change in the control group. Moreover, while all 3 groups experienced an increase in hip muscle strength (P =.001), the IASTM and FR groups exhibited a greater increase compared with exercise alone (P =.001). Conclusions: Based on these findings, exercise improves pain, range of motion, and muscle strength in athletes with ITB tightness, and IASTM, and FR techniques enhanced exercise effects but did not differ from one another. While our study demonstrated that both IASTM and FR techniques significantly enhance the benefits of exercise for athletes with ITB tightness, further research could delve into the long-term effects of these interventions. [ABSTRACT FROM AUTHOR]

OBJECTIVE: To determine i) pain phenotypes (PP) in people with early-stage knee osteoarthritis (EKOA); ii) the longitudinal association between the phenotypes and pain worsening at two years. DESIGN: We studied participants with EKOA from the Multicenter Osteoarthritis Study defined as pain intensity ≤3/10, Kellgren and Lawrence grade ≤2, intermittent pain none to sometimes, and no constant pain. Two models of PP were explored. Model A included pressure pain thresholds, temporal summation, conditioned pain modulation, pain catastrophizing, sleep quality, depression, and widespread pain (WSP). In Model B, gait characteristics, quadriceps strength, comorbidities, and magnetic resonance imaging features were added to Model A. Latent Class Analysis was used to create phenotypes, and logistic regression was used to determine their association with pain worsening. RESULTS: 750 individuals (60% females), mean age [standard deviation (SD)]: 60.3 (9.4) were included in Model A and 333 individuals (60% females), mean age (SD): 59.4 (8.1) in Model B. 3-class and 4-class solutions were chosen for Model A and Model B. In Model A, the most severe phenotype was dominated by psychosocial factors, WSP, and measures of nervous system sensitization. Similarly in Model B, the Model A phenotype plus gait variables, quadriceps strength, and comorbidities were dominant. Surprisingly, none of the phenotypes in either model had a significant relationship with pain worsening. CONCLUSION: Phenotypes based upon various factors thought to be important for the pain experience were identified in those with EKOA but were not significantly related to pain worsening. These phenotypes require validation with clinically relevant endpoints.

AbstractPurposeMaterials and methodsResultsConclusionsTo evaluate the efficacy of an immersive movement visualization intervention in patients with hemophilia and hemophilic knee arthropathy.Randomized, single-blind clinical study. Twenty-eight patients with hemophilia were recruited. Patients were randomized to an experimental group (four weeks of immersive movement visualization) and a control group (no intervention). The intensity of pain, pressure pain threshold in the knee, tibialis anterior muscle, lower back level, conditioned pain modulation, range of knee motion, and lower limb functionality were evaluated.There were statistically significant differences in the intergroup effect on knee pain intensity (F = 23.71; p < 0.001) and lower limb functionality (F = 7.11; p = 0.003). 42.86% of the patients in the experimental group exhibited changes greater than the minimum detectable change (MDC) in functionality. 39.29% of the patients subject to the intervention experienced changes greater than the MDC in the knee pressure pain threshold.Immersive motion visualization can improve the intensity of joint pain and functionality in patients with hemophilic knee arthropathy. Functionality, pressure pain threshold, and pain intensity improved in those patients who conducted immersive movement visualization.Implications for rehabilitationImmersive visualization of movement significantly improves intensity of joint pain, functionality, pressure pain threshold, joint health, and conditioned pain modulation in patients with hemophilic knee arthropathy.The fact that it is a therapy without potential aversive stimuli makes it a possible access pathway for patients with high levels of kinesiophobia and/or catastrophism.This low-cost, home-based technology allows its use in patients far from hemophilia reference centers or with difficult access to physiotherapy treatments.The immersive visualization of movement influences the democratization of treatment, in accordance with the WHO's Sustainable Development Goal 3 (health and well-being for all).Immersive visualization of movement significantly improves intensity of joint pain, functionality, pressure pain threshold, joint health, and conditioned pain modulation in patients with hemophilic knee arthropathy.The fact that it is a therapy without potential aversive stimuli makes it a possible access pathway for patients with high levels of kinesiophobia and/or catastrophism.This low-cost, home-based technology allows its use in patients far from hemophilia reference centers or with difficult access to physiotherapy treatments.The immersive visualization of movement influences the democratization of treatment, in accordance with the WHO's Sustainable Development Goal 3 (health and well-being for all). [ABSTRACT FROM AUTHOR]

Introduction: Previously, we had observed that immediate pain reduction after one acupuncture treatment was associated with high temporal summation of pain (TS) at a pain free control site and younger age in a mixed population of chronic pain patients. The aim of the present study was to verify these results in chronic non-specific low back pain (LBP) and to collect pilot data on the association between TS and the response to an acupuncture series. Methods: TS at a pain free control site (back of dominant hand) and at the pain site was quantified by the pin-prick induced wind-up ratio (WUR) in 60 LBP patients aged 50 years or younger. Response to one acupuncture treatment was assessed by change in pain intensity and pressure pain threshold (PPT) at the pain site. The primary hypothesis was that a high TS (WUR > 2.5) would be associated with a clinically relevant reduction in pain intensity of at least 30%. In study part two, 26 patients received nine additional treatments. Response to the acupuncture series was assessed by the pain intensity during the last week, the PPT and the Hannover functional ability questionnaire (FFbH-R). Results: An immediate reduction in pain intensity of at least 30% was frequent irrespective of TS at the control site (low vs. high TS 58% vs. 72%, p = 0.266). High TS at the pain site was also not significantly associated with a clinically relevant immediate reduction in pain intensity (low vs. high TS 46% vs. 73%, p = 0.064). The PPT was not changed after one acupuncture treatment. Study part two did not reveal a consistent association between TS at the control site and any of the outcome measures but also a trend toward a higher chance for a clinically relevant response along with low TS at the pain site. Conclusion: Our results do not suggest an important role of TS for predicting a clinically important acupuncture effect or the response to a series of 10 acupuncture treatments in patients with chronic non-specific LBP. Overall high response rates imply that acupuncture is a suitable treatment option for LBP patients irrespective of their TS. [ABSTRACT FROM AUTHOR]

Background: Keen Osteoarthritis (KOA) is a common chronic disabling disease characterized by joint pain and dysfunction, which seriously affects patients' quality of life. Recent studies have shown that transcranial direct current stimulation (tDCS) was a promising treatment for KOA. Purpose: Investigate the effects of tDCS on pain and physical function in patients with KOA. Methods: Randomized controlled trials related to tDCS and KOA were systematically searched in the PubMed, Embase, Medline, Cochrane Library, CINHL, and Web of Science databases from inception to July 23, 2024. The pain intensity was evaluated using the visual analog scale or the numeric rating scale, and the pain sensitivity was assessed using conditioned pain modulation, pressure pain threshold, heat pain threshold, or heat pain tolerance. The physical function outcome was evaluated using the Western Ontario and McMaster Universities Osteoarthritis Index or the Knee injury and Osteoarthritis Outcome Score. Statistical analysis was performed using Review Manager 5.4. Results: Seven studies with a total of 503 participants were included. Compared to sham tDCS, tDCS was effective in reducing the short-term pain intensity (SMD: -0.58; 95% CI: -1.02, -0.14; p = 0.01) and pain sensitivity (SMD: -0.43; 95% CI: -0.70, -0.16; p = 0.002) but failed to significantly improve the long-term pain intensity (SMD: -0.26; 95% CI: -0.59, 0.08; p = 0.13) in KOA patients. In addition, tDCS did not significantly improve the short-term (SMD: -0.13; 95% CI: -0.35, 0.08; p = 0.22) and long-term (SMD: 0.02; 95% CI: -0.22, 0.25; p = 0.90) physical function in patients with KOA. Conclusions: The tDCS can reduce short-term pain intensity and sensitivity but fails to significantly relieve long-term pain intensity and improve the physical function in patients with KOA. Thus, tDCS may be a potential therapeutic tool to reduce short-term pain intensity and pain sensitivity in patients with KOA. [ABSTRACT FROM AUTHOR]

Background: The motor neuron survival protein performs numerous cellular functions; hence, spinal muscular atrophy (SMA) is considered to be a multi-organ disease with possible sensory system damage. The controversy surrounding the presence of sensory disturbances, prompted us to conduct standard electrophysiological studies and assess the sensory thresholds for different modalities in adults with SMA types 2 and 3. The study group consisted of 44 adult SMA patients (types 2 and 3). All patients underwent neurological examination using the Hammersmith Functional Motor Scale – Expanded (HFMSE). Standard sensory electrophysiological studies in the ulnar nerve and the estimation of vibratory, temperature, and warm- and cold-induced pain thresholds with temperature dispersion assessment were performed using quantitative sensory testing (QST). Results: The most repeatable result was the high amplitude of the sensory nerve action potentials (SNAP) in SMA patients compared to controls. This was higher in type 2 patients compared to type 3a and 3b patients and patients with low HFSME scores. Patients with SMA, especially type 3b presented a longer sensory latency and slower conduction velocity than did controls. Cold pain threshold was higher and warm dispersion larger in SMA. The vibratory limit was higher in patients with high HFSME scores. Conclusions: A high SNAP amplitude suggests sensory fibre hyperactivity, which may be based on overactivation of metabolic pathways as an adaptive mechanism in response to SMN protein deficiency with additionally coexisting small C- and A-delta fibre damage. SMA patients seem to have a concomitant, mild demyelinating process present at the early SMA stage. [ABSTRACT FROM AUTHOR]

Objective: The aim of the study is to evaluate whether the application of an interfascial injection with dextrose water could result in reduced pain and improved shoulder function and range of motion. Design: This is a double-blind randomized controlled trial. Thirty-five patients with chronic shoulder pain were randomly assigned to receive either an interfascial injection of 10 mL of 10% dextrose water guided by ultrasound or a sham injection of 0.5 mL of 10% dextrose water into the subcutaneous layer. All patients received education on a home program of self-massage and self-stretching. Shoulder pain, shoulder range of motion, and neck and shoulder function were measured before injection and at 4 and 12 wks after injection. Results: Both groups showed significant improvements in visual analog scale scores at 12-wk follow-up. The interfascial injection group exhibited a significant pain reduction compared with the sham group at the 12-wks follow-up. No between-group differences were observed in shoulder range of motion, pain threshold, and neck and shoulder function. Conclusions: Interfascial injection is effective in decreasing pain in patients with myofascial pain syndrome. [ABSTRACT FROM AUTHOR]

Objectives: Effective posttonsillectomy analgesia is crucial for patient comfort and recovery. Fentanyl, notable for its potency, rapid action, and lipophilicity, has been successfully used in various procedures through multiple administration routes. However, the use of its nebulized form for posttonsillectomy pain has not been extensively explored. This study sought to compare the analgesic efficacy, onset time, and complications between nebulized and intravenous fentanyl in posttonsillectomy patients. Methods and Methods: In this randomized controlled trial, adult patients who underwent tonsillectomy were assigned to either an intravenous fentanyl group (1 mcg/kg) or a nebulized fentanyl group (4 mcg/kg). In both groups, fentanyl was administered when pain scores exceeded three. Pain levels were monitored every 5 minutes until they fell below four. The study also recorded the duration until the next analgesia request and noted complications (such as respiratory depression, bradycardia, chest tightness, drowsiness, nausea, pruritus, sweating, and flushing) within 24 hours. Patient exclusions were based on predetermined criteria. Results: From an initial cohort of 59 patients, 22 in the intravenous group and 27 in the nebulizer group were eligible for analysis after applying the exclusion criteria. The nebulizer group exhibited a significantly prolonged period before the next analgesia request, with a median of 683.5 minutes (interquartile range 260-1440), in contrast to the 326.7 minutes (145.0-504.7) observed in the intravenous group (P =.009). The time to achieve a pain score less than 4 and the incidence of side effects did not differ significantly between the groups. Conclusion: Nebulized fentanyl provided a longer duration of analgesia than intravenous fentanyl in posttonsillectomy pain management, with similar onset times and side effect profiles. These findings underscore the potential of nebulized fentanyl as an effective alternative for pain control in posttonsillectomy patients. [ABSTRACT FROM AUTHOR]

Depression and chronic pain frequent co-occur, exacerbating each other's symptoms and hindering treatment. Emerging studies have highlighted abnormal gut microbiota in both conditions. Previous studies have demonstrated the clinical effectiveness of electro-acupuncture (EA) in managing these conditions, yet the underlying mechanisms remain elusive. Spared nerve injury (SNI) was employed to induce chronic pain and depression-like behavior. Rats were randomly assigned to sham SNI (SS), SNI, and EA groups. SNI surgery was performed on all rats, except those in SS group, which underwent sham SNI surgery. Then EA group received 5 weeks of EA treatment. Pain and depression-like behavior were assessed through paw withdrawal threshold, sucrose-preference test, and forced swim test. Gut microbiota composition was analyzed via 16S rDNA sequencing. Brain-Derived Neurotrophic Factor (BDNF) and acetylation-related proteins in the medial prefrontal cortex (mPFC) were evaluated through enzyme-linked immunosorbent assay and western blot. EA treatment significantly ameliorated pain and depression-like behavior. The 16S rDNA sequencing showed EA modulated gut microbiota composition, increased short-chain fatty acids (SCFAs)-producing bacteria, including Akkermansi, Ruminococcaceae and Lachnospiraceae family, particularly Akkermansia. Furthermore, EA increased BDNF, AcH3 and decreased HDAC2 in mPFC. Notably, SCFAs-producing bacteria exhibited a negative correlation with HDAC2 levels. This study exclusively investigated microbiota differences resulting from EA stimulation, without delving into the functional variations brought about by these microbial distinctions. The therapeutic effects of EA on the comorbidity of chronic pain and depression may involve the modulation of the gut microbiota, resulting in histone acetylation changes and upregulation of BDNF. • EA ameliorated pain and depression-like behaviors in SNI rats. • EA modulated the gut microbiota, increased the abundance of SCFAs-producing bacteria, particularly Akkermansia- muciniphila. • EA inhibited histone deacetylase in SNI rats. [ABSTRACT FROM AUTHOR]

In the diagnosis of migraine, which is a neurovascular disease, gadolinium-based contrast agents (GBCAs) are used to rule out more serious conditions. On the other hand, it remains unclear as a scientific gap whether GBCAs may trigger migraine-related pain. The aim of this study was to investigate the effect of GBCAs on mechanical and thermal pain behaviour in a nitroglycerin (NTG)-induced migraine model in mice. NTG (10 mg/kg) was administered intraperitoneally to adult (6–8 weeks old) BALB/c mice 2 h before behavioral tests 5 times every other day on days 1st, 3rd, 5th and 9th to induce migraine model (N = 50). As GBCAs, gadobenate dimeglumine (linear-ionic), Gadodiamide (linear-nonionic), and gadobutrol (macrocyclic-nonionic) were delivered intravenously through the tail vein of mice for 5 days on test days. Mechanical pain threshold (plantar and facial withdrawal threshold) was evaluated by plantar von Frey and periorbital von Frey tests on days 1st, 5th, and 9th, and thermal pain threshold (latency) was evaluated by hot plate and cold plate tests on days 3rd and 7th. There was a statistically significant increase in mechanical and thermal hyperalgesia in NTG administered groups compared to the control group. Gadodiamide, gadobutrol and gadobenate dimeglumine administration significantly decreased latency, paw and facial withdrawal threshold (0.18 ± 0.05, 0.17 ± 0.07, 0.16 ± 0.09; 9th day values respectively) compared to NTG group (0.27 ± 0.05). The results of this in vivo study show that GBCAs produce effects that may trigger migraine attacks in migraine. It is recommended that these effects be further investigated and supported by further clinical studies. [ABSTRACT FROM AUTHOR]

Preoperative pain sensitivity (PPS) can be associated with postsurgical pain. However, estimates of this association are scarce. Confirming this correlation is essential to identifying patients at high risk for severe postoperative pain and for developing analgesic strategy. This systematic review and meta-analysis summarises PPS and assessed its correlation with postoperative pain. PubMed, Scopus, Cochrane Library, and PsycINFO were searched up to October 1, 2023, for studies reporting the association between PPS and postsurgical pain. Two authors abstracted estimates of the effect of each method independently. A random-effects model was used to combine data. Subgroup analyses were performed to investigate the effect of pain types and surgical procedures on outcomes. A total of 70 prospective observational studies were included. A meta-analysis of 50 studies was performed. Postoperative pain was negatively associated with pressure pain threshold (PPT; r =–0.15, 95% confidence interval [CI] –0.23 to –0.07]) and electrical pain threshold (EPT; r =–0.28, 95% CI –0.42 to –0.14), but positively correlated with temporal summation of pain (TSP; r =0.21, 95% CI 0.12–0.30) and Pain Sensitivity Questionnaire (PSQ; r =0.25, 95% CI 0.13–0.37). Subgroup analysis showed that only TSP was associated with acute and chronic postoperative pain, whereas PPT, EPT, and PSQ were only associated with acute pain. A multilevel (three-level) meta-analysis showed that PSQ was not associated with postoperative pain. Lower PPT and EPT, and higher TSP are associated with acute postoperative pain while only TSP is associated with chronic postoperative pain. Patients with abnormal preoperative pain sensitivity should be identified by clinicians to adopt early interventions for effective analgesia. PROSPERO (CRD42023465727). [ABSTRACT FROM AUTHOR]

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• The PFC is a target for the treatment of NPP. • Two weeks of 10 Hz rTMS of PFC can relief CCI-induced NPP. • 10 Hz rTMS can induce microglia polarization to M2 in the PFC and sciatic nerve. • 10 Hz rTMS can reduce the pro-inflammatory and increase the anti-inflammatory factors. • The abscopal effect of rTMS relates to microglial polarization and neuroinflammation. The study aimed to assess the analgesic effect of 10 Hz repetitive transcranial magnetic stimulation (rTMS) targeted to the prefrontal cortex (PFC) region on neuropathic pain (NPP) in rats with chronic constriction injury (CCI) of the sciatic nerve, and to investigate the possible underlying mechanism. Rats were randomly divided into three groups: sham operation, CCI, and rTMS. In the latter group, rTMS was applied to the left PFC. Von Frey fibres were used to measure the paw withdrawal mechanical threshold (PWMT). At the end of the treatment, immunofluorescence and western blotting were applied to detect the expression of M1 and M2 polarisation markers in microglia in the left PFC and sciatic nerve. ELISA was further used to detect the concentrations of inflammation-related cytokines. The results showed that CCI caused NPP in rats, reduced the pain threshold, promoted microglial polarisation to the M1 phenotype, and increased the secretion of pro-inflammatory and anti-inflammatory factors. Moreover, 10 Hz rTMS to the PFC was shown to improve NPP induced by CCI, induce microglial polarisation to M2, reduce the secretion of pro-inflammatory factors, and further increase the secretion of anti-inflammatory factors. Our data suggest that 10 Hz rTMS can alleviate CCI-induced neuropathic pain, while the underlying mechanism may potentially be related to the regulation of microglial M1-to-M2-type polarisation to regulate neuroinflammation. [ABSTRACT FROM AUTHOR]

BACKGROUND: Patients with degenerative cervical spondylosis often suffer from changed varicosity of the cervical spine, unbalanced neck-shoulder muscular strength, and descending power. OBJECTIVE: To probe into the correlation between sagittal curvature parameters and pain threshold for neck-shoulder muscles in degenerative cervical spondylosis. METHODS: Totally 50 patients with degenerative cervical spondylosis received treatment at the 3D Printed Outpatient Center of Shanghai Ninth People's Hospital, Shanghai Jiao Tong University School of Medicine from January 2022 to March 2023 were included in the study. After excluding the 10 patients of cervical lateral projection that failed to meet the measurement conditions, the cervical lateral projections were shot to measure the following iconography parameters: Borden value and C2-7 Cobb angle as well as pain thresholds on the midpoint of the superior trapezius muscle in bilateral bundles and at 1 cm beside the C5-6 interspike. The correlation between sagittal curvature parameters and pain threshold of neck-shoulder muscles in degenerative cervical spondylosis was analyzed. RESULTS AND CONCLUSION: (1) The Borden value of sagittal curvature showed a moderately positive correlation with the bundle pain threshold in the left upper trapezius muscle, the bundle pain threshold in the right upper trapezius muscle, and the pain threshold at the 1 cm of the left side beside the C5-6 interspike (r=0.498, P < 0.01; r=0.448, P < 0.05; r=0.405, P < 0.05) and a weak positive correlation with the pain threshold at the 1 cm of the right side beside the C5-6 interspike (r=0.322, P < 0.05). (2) The C2-7 Cobb angle showed a weak positive correlation with the left squared myalgia threshold (r=0.355, P < 0.05), and there was no correlation with the pain threshold of the left trapezius muscle and the pain threshold at the 1 cm of both sides beside the C5-6 interspike. (3) There was a correlation between the pain threshold of the neck-shoulder muscles, and a high correlation between the pain threshold of the left and right muscles and the pain threshold within the left and right side muscles, indicating that the neck-shoulder muscles are consistent and may be related to the coordination of the neck-shoulder movements. [ABSTRACT FROM AUTHOR]

Background: Temporomandibular joint has biomechanical and neurological interactions with cervical region in a complex functioning that is addressed as cranio-cervical mandibular system. Subjects and methods: In a prospective cohort study of 67 patients, their mean age 24.3 ± 5.6 years of both genders with temporomandibular disorder "bruxism," patients had fulfilled a questionnaire regarding bruxism manifestations. Pain pressure algometer was used to assess pain pressure threshold for trigger point in masseter, temporalis, sternocleidomastoid, and trapezius, and bubble inclinometer was used to assess cervical proprioception for all cervical ranges. Results: There was a statistical significant indirect weak correlation between proprioception error of cervical flexion and pain pressure threshold of masseter (r = − 0.333) (p = 0.006), between proprioception error of cervical flexion and pain pressure threshold of trapezius (r = − 0.363) (p = 0.003), and also between proprioception error of cervical left-side bending and pain pressure threshold of trapezius (r − 0.298; p 0.014), while there was significant direct weak correlation between proprioception error of cervical left rotation and cervical bending to left (r 0.315; p 0.009), where the p-value was < 0.05. Conclusion: The study proved that temporomandibular joint pain was correlated with impaired neck proprioception in whom with bruxism. Trial registration: NCT05657353. Registered 28 November 2022 — prospectively registered, https://register.clinicaltrials.gov/prs/app/action/LoginUser?ts=1&cx=-jg9qo4. [ABSTRACT FROM AUTHOR]

Introduction: Chronic muscle pain is common in myotonic dystrophies (DM). Little is known about its pathophysiology. We aimed to investigate the characteristics of the neuropathic pain component contributing contributes to the pathogenesis of chronic pain in DM. Methods: Twenty-one DM1 and 32 DM2 patients completed pain questionnaires (Brief pain inventory--BPI, PAIN-DETECT, pain disability index--PDI) and underwent neurological examination, nerve conduction studies (NCS), quantitative sensory testing (QST, dorsum of the right hand and right thigh) and skin biopsy to determine the intraepidermal nerve fiber density (IENFD, distal and proximal site of lower extremity). NCS and QST results at the thigh were compared to 27 healthy controls and IENFD and QST at the dorsum of the hand to published reference values. Results: The sensory profile of DM2 patients was characterized by a loss in thermal and mechanical detection, while DM1 patients showed reduced mechanical and heat pain thresholds and higher mechanical pain sensitivity. Both DM groups showed pressure hyperalgesia. IENFD was reduced in 63% of DM1 patients and 50% of DM2. The slightly higher pain interference and disability found in DM2 was rather due to age difference than disease. Conclusion: Similar pain mechanisms likely occur in both DM1 and DM2, even though a tendency toward more pain sensitivity was observed in DM1 and more sensory loss in DM2. Both QST and reduced IENFD highlight the presence of peripheral nerve damage in DM. This must be considered for the best pain management strategies. [ABSTRACT FROM AUTHOR]

Introduction: Post-activation performance enhancement (PAPE) cannot be clearly distinguished from and may be explained in large by warm-up effects. To disentangle PAPE from a systemic warm-up effect, we conducted three randomized crossover trials (RCT). Methods: Each RCT consisted of a familiarization/one-repetition-maximum (1RM) assessment session followed by two interventional sessions (random order). In Study I, 18 participants (age: 26 ± 4 years; height: 1.84 ± 0.06 m; mass: 83.7 ± 8.7 kg; Squat-1RM: 146 ± 19 kg) performed either a 3-s isometric squat at 130%1RM or a 6-s isometric squat at 65%1RM. In Study II, 28 participants (11 female; age: 23 ± 3 years; height: 1.77 ± 0.08 m; mass: 76.5 ± 10.4 kg; Squat-1RM: 109 ± 38 kg) completed either Squat (3 × 3 repetitions, 85%1RM) or local electromyostimulation of the quadriceps muscle (85% of individual pain threshold). In Study III, 20 participants (6 female, age: 25.0 ± 3.5 years, mass: 78.5 ± 15.8 kg, height: 1.75 ± 0.08 m; SQ-1RM: 114 ± 33 kg, chest-press-1RM: 74 ± 29 kg) performed either squats or chest press (4 repetitions, 80%1RM). Counter-Movement-Jump height (CMJ) was assessed after a general (PRE) and/or muscle-specific warm-up (POST_WU) and for up to 11 min after the PAPE protocols. To identify possible differences in CMJ between the experimental conditions, mixed-design ANOVA models were used for each study individually, with condition and timemodelled as fixed effects, while participants were included as a random effect blocking factor. The level of statistical significance was set at a = 5%. Results: In studies I and II, significant effects for time (p < 0.05, p 2 = 0.06 and p < 0.001, p 2 = 0.43) were found with the highest CMJ compared to all other time points at PRE (=8.2 ± 4.6%, standardized mean difference: =0.39), regardless of condition. In study III, no significant effects were observed. Discussion: Thus, PAPE protocols do not further improve jumping performance compared to a general and muscle-specific traditional warm-up. Prior to tasks requiring explosive strength, general and sport-specific warm-up strategies should be used. [ABSTRACT FROM AUTHOR]

Background: Acute physical activity often induces an acute reduction in pain sensitivity known as exercise induced hypoalgesia (EIH). The aim of this study was to investigate the effects of a high intensity functional training (HIFT) on EIH compared to a control session. Methods: 50 (age: 26.0 ± 2.7; 23 female) participants successfully conducted this study consisting of a pre-experimental test as well as a 12-minute HIFT (body-weight exercises) and a 12-minute control (supervised breathing) session in a randomized crossover design. Pre and post, pressure pain thresholds (PPT) were measured at the ankles, knees, elbows, and forehead. Results: The HIFT resulted in a relative maximum and average heart rate of 96.2% (± 3.6%) and 91.1% (± 4.2%), respectively, and maximum and average RPE values of 19.1 (± 1.2) and 16.2 (± 1.4), respectively. Results reveal a significant 'Intervention' × 'Time point' interaction (p < 0.001) for PPT (pooled for one average value) with hypoalgesia observed following the HIFT (p < 0.001; pre: 56.0 ± 16.8, post: 61.6 ± 19.0 [Newton]) and no change following the control (p = 0.067; pre: 56.6 ± 18.4, post: 55.3 ± 18.9 [Newton]). Further, a significant 'Time' × 'Intervention' × 'Landmark' interaction effect (p = 0.024) is observed and all landmarks showed significant hypoalgesia following HIFT (p < 0.01), except for the right elbow and forehead. Following control, no hypoalgesia was observed at any landmark. Analysing male and female participants separately, it was observed that EIH occured only in men. Conclusion: A HIFT using bodyweight exercises reduces pain sensitivity. Hence, combining strength and aerobically demanding exercises in a short but high intensity manner, as done in HIFT, can be seen as a usable tool to induce hypoalgesia. Yet, these results were observed only in male participants, necessitating future sex-specific research. Trial registration: DRKS00034391, retrospectively registered on the 4th of June 2024. [ABSTRACT FROM AUTHOR]

We used light-sensitive drugs to identify the brain region-specific role of mGlu5 metabotropic glutamate receptors in the control of pain. Optical activation of systemic JF-NP-26, a caged, normally inactive, negative allosteric modulator (NAM) of mGlu5 receptors, in cingulate, prelimbic, and infralimbic cortices and thalamus inhibited neuropathic pain hypersensitivity. Systemic treatment of alloswitch-1, an intrinsically active mGlu5 receptor NAM, caused analgesia, and the effect was reversed by light-induced drug inactivation in the prelimbic and infralimbic cortices, and thalamus. This demonstrates that mGlu5 receptor blockade in the medial prefrontal cortex and thalamus is both sufficient and necessary for the analgesic activity of mGlu5 receptor antagonists. Surprisingly, when the light was delivered in the basolateral amygdala, local activation of systemic JF-NP-26 reduced pain thresholds, whereas inactivation of alloswitch-1 enhanced analgesia. Electrophysiological analysis showed that alloswitch-1 increased excitatory synaptic responses in prelimbic pyramidal neurons evoked by stimulation of presumed BLA input, and decreased BLA-driven feedforward inhibition of amygdala output neurons. Both effects were reversed by optical silencing and reinstated by optical reactivation of alloswitch-1. These findings demonstrate for the first time that the action of mGlu5 receptors in the pain neuraxis is not homogenous, and suggest that blockade of mGlu5 receptors in the BLA may limit the overall analgesic activity of mGlu5 receptor antagonists. This could explain the suboptimal effect of mGlu5 NAMs on pain in human studies and validate photopharmacology as an important tool to determine ideal target sites for systemic drugs. [ABSTRACT FROM AUTHOR]

The nociceptive withdrawal reflex (NWR) is a protective limb withdrawal response triggered by painful stimuli, used to assess spinal nociceptive excitability. Conventionally, the NWR is understood as having two reflex responses: a short-latency Aβ-mediated response, considered tactile, and a longer-latency Aδ-mediated response, considered nociceptive. However, nociceptors with conduction velocities similar to Aβ tactile afferents have been identified in human skin. In this study, we investigated the effect of a preferential conduction block of Aβ fibers on pain perception and NWR signaling evoked by intradermal electrical stimulation in healthy participants. We recorded a total of 198 NWR responses in the intact condition, and no dual reflex responses occurred within our latency bandwidth (50–150 ms). The current required to elicit the NWR was higher than the perceptual pain threshold, indicating that NWR did not occur before pain was felt. In the block condition, when the Aβ-mediated tuning fork sensation was lost while Aδ-mediated nonpainful cooling was still detectable (albeit reduced), we observed that the reflex was abolished. Further, short-latency electrical pain intensity at pre-block thresholds was greatly reduced, with any residual pain sensation having a longer latency. Although electrical pain was unaffected at suprathreshold current, the reflex could not be evoked despite a two-fold increase in the pre-block current and a five-fold increase in the pre-block pulse duration. These observations lend support to the possible involvement of Aβ-fiber inputs in pain and reflex signaling. [ABSTRACT FROM AUTHOR]

Background: Fibromyalgia (FM) is a complex multidimensional disorder primarily characterized by chronic widespread pain, significantly affecting patients' quality of life. FM is associated with some clinical signs found with quantitative sensory testing (QST), sleep disturbance, or psychological problems. This study aims to explore the associations between pressure pain thresholds (PPTs), conditioned pain modulation (CPM), clinical status, and sleep quality in FM patients, offering insights for better clinical management and assessment tools. Methods: This secondary analysis utilized data from a clinical trial involving 129 FM patients. Various assessments, including the Fibromyalgia Impact Questionnaire (FIQ), Pain Catastrophizing Scale (PCS), State-Trait Anxiety Inventory (STAI), and Jenkins Sleep Scale (JSS), were employed to evaluate the clinical and psychological status and sleep quality. PPTs and CPM were measured to understand their relationship with clinical parameters. Results: Our findings revealed that PPTs and CPM are not significantly associated with the clinical status or sleep quality of FM patients. Instead, pain catastrophizing and anxiety state showed a stronger correlation with the impact of fibromyalgia and sleep disturbances. These results highlight the importance of psychological and cognitive factors in managing FM. Conclusions: The study suggests that while PPTs and CPM may not be reliable biomarkers for clinical status in FM, the use of comprehensive assessments including FIQ, PCS, STAI, and JSS can provide a more accurate evaluation of patients' condition. These tools are cost-effective, can be self-administered, and facilitate a holistic approach to FM management, emphasizing the need for personalized treatment plans. [ABSTRACT FROM AUTHOR]

Oxaliplatin (OXA) as the platinum-based agent induces the cumulative neuropathy including functional impairment and neuropathic pain. OXA treatment triggered oxidative stress and inflammatory reaction in the spinal cord. Puerarin as a natural product has the neuroprotective effect on neuropathic pain. Hence, the roles and mechanisms of Pue on OXA induced neuropathic pain were studied. In this study, OXA-induced neuropathic pain mouse model was constructed by oxaliplatin injection for 5 consecutive days and two cycles. Pue (10 mg/kg) was administered intraperitoneally for seven consecutive days. The changes of behavior, morphology and levels of related proteins were detected. As a result, OXA-induced mice exhibited as the increased pain hypersensitivity, the impaired motor coordination, the activated NLRP3 inflammasome mediated inflammation and the suppressed nuclear factor erythroid 2-related factor 2 (Nrf2) mediated antioxidative reaction in the spinal cord (P<0.05 vs Control). After Pue administration, the mechanical pain threshold, thermal pain latency, spontaneous pain number and motor latency were improved (P<0.05 vs OXA). In the spinal cord, Pue administration reduced the levels of inflammatory elements, increased the levels of antioxidative elements and decreased the levels of oxidative factors (P<0.05 vs OXA). Furthermore, Pue also bind with Nrf2 and increased the association of Nrf2 to glutathione peroxidase 4 (GPX4). In summary, Pue alleviates oxaliplatin induced neuropathic pain by enhancing Nrf2/GPX4-mediated antioxidant response and suppressing inflammatory reaction in the spinal cord. [ABSTRACT FROM AUTHOR]

The purpose of this study was to determine: (1) whether physically active virtual reality (VR) games exert an acute hypoaglesic effect on the thigh and bicep compared to a non-active VR game and an exercise only condition matched for exercise intensity in healthy individuals, and (2) whether movement variables during gameplay are associated with the hypoalgesic effect of the games. Twenty young adults completed five separate study sessions, with each session devoted to playing one head-mounted display VR game or stationary cycling for 15 minutes. The games included Holopoint at level 2 and level 3, Hot Squat, and Relax Walk. Pressure pain thresholds at the thigh and bicep were measured pre and post VR gameplay and cycling. Participants wore a heart rate monitor and accelerometers on the wrist and thigh during play to measure the intensity and quantity of movement. Repeated measures ANOVAs revealed that pressure pain thresholds on the bicep increased from pre to posttest for each condition. The results also revealed that pressure pain thresholds on the thigh increased only for the conditions eliciting the greatest cardiovascular response, which included Holopoint at level 3, Hot Squat, and cycling. Bivariate correlations indicated that moderate to vigorous physical activity of the thigh was associated with pain reduction at the thigh during Holopoint. These results revealed that active VR games and exercise exerted a more widespread hypoalgesic effect compared to the non-active VR game, which was likely driven in part by the intensity and quantity of movement during gameplay. [ABSTRACT FROM AUTHOR]

Background: The neurodegenerative process in Parkinson's disease (PD) affects both dopaminergic and non-dopaminergic structures, which determine the wide range of motor and non-motor symptoms (NMS), including different types of pain. Diverse mechanisms contribute to pain in PD. Abnormal nociceptive processing is considered a distinctive feature of the disease. Objective: In the present study, we used a validated PD-specific pain assessment tool to investigate self-reported pain in PDpatients and to analyze the association with the objective pain threshold. Methods: The RIII component of the nociceptive flexor reflex was assessed in 35 patients with PD and was compared to 40 healthy controls. Self-reported pain was measured using the Bulgarian version of the King's Parkinson's Disease Pain Scale (KPPS-BG). A correlation analysis was used to investigate the relationship between the objective nociceptive threshold and PD pain as assessed by KPPS-BG. Results: PD patients had a significantly lower RIII threshold than control individuals (the mean SD value was 6.24 ± 1.39 vs. 10.33 ± 1.64) when assessed in the "off" state. A statistically significant (p < 0.05) fairly negative Spearman's correlation was observed between the decreased spinal nociceptive threshold and fluctuation-related pain (-0.31). Domain 4, "nocturnal pain" (-0.21), and the KPPS-BG total score (-0.21) showed a weak negative correlation. An insignificant positive correlation was found between domain 6--"discoloration, edema/swelling"--and the RIII threshold. A higher Movement Disorders Society Unified Parkinson's Disease Rating Scale (MDS-UPDRS) part III score and modified Hoehn and Yahr (H&Y) scale are associated with a decreased nociceptive flexor reflex threshold. Conclusion: The results of the present study demonstrate the important role of increased spinal nociception in the occurrence of pain, which is associated with fluctuations and, to a lesser extent, nocturnal pain. [ABSTRACT FROM AUTHOR]

Background: The center of pressure (COP) excursion parameters are recognized as risk factors for the etiology and development of patellofemoral pain (PFP). The purpose of the present study measures the effect of pain exacerbation on COP excursion, and the correlation between pain intensity and COP excursion in women with PFP during single leg squat (SLS). Methods: Sixty patients with PFP participated in this cross-sectional study. The outcome measures were included pain intensity and COP excursion which evaluated in pre and post pain exacerbation during SLS. The COP parameters were evaluated during single leg squat in 60° of knee flexion. A paired t-test and MANOVA was used to compare pain intensity and COP excursion between the two conditions, respectively. Furthermore, A Pearson's correlation matrix was used to examine the relationship between pain intensity with COP excursion. Results: Statistical analysis showed that pain intensity (t = − 16.655, p < 0.001) and COP excursion (Wilks' Lambda = 0.225, p < 0.001) with medium effect size increased after PFJ loading. In addition, an excellent positive correlation was observed between increased in pain intensity and COP excursion (P < 0.001, r > 0.80). Conclusion: After PFJ loading, women with PFP presented increases in the pain intensity, COP excursions, and sway velocity. In addition, there was an association between the increase in pain intensity and COP excursions. Clinicians aiming to improve postural control of patients with PFP could use kinesio taping as a short-term intervention and balance training to improvements in postural control at medium and long-term. Furthermore, emphasizing psychological factors to reducing kinesiophobia can be useful to restoring proper movement pattern, reducing pain and improving symptoms. [ABSTRACT FROM AUTHOR]

Introduction: Dysmenorrhea is associated with increased risk of chronic pain and hyperalgesia. Menstruating individuals with dysmenorrhea are more likely to have elevated pain reactivity when experiencing experimental pain, than those without. However, no study has examined intragroup differences in reactions to experimentally induced pain for individuals with dysmenorrhea. The main aim of this study was to examine the relative roles of dysmenorrhea severity and interference in the experience of experimentally-induced pain. Methods: Participants were 120 menstruating individuals involved in a larger research study examining the influence of expectations on experimentallyinduced pain. As part of the study, participants completed an online questionnaire regarding demographic and menstrual information and participated in a cold pressor task. Participants were randomized into four groups based on the manipulation of two independent variables: (1) high vs. low expectations about pain severity (pain-expectations); (2) and high vs. low expectations about one's pain tolerance (self-expectations). Participants verbally rated their pain severity throughout the cold pressor task using a 0-10 scale. Regression analyses were conducted examining the relationships between dysmenorrhea experience (i.e., average severity and interference) and cold pressor data [pain severity ratings and pain tolerance (i.e., total time in the cold pressor)], controlling for the manipulated expectations and age. Then, moderation analyses were conducted examining expectation group differences. Results: When controlling for manipulated expectations and age, dysmenorrhea severity significantly predicted initial pain severity rating (p = 0.022) but did not predict final pain severity rating (p = 0.263) or pain tolerance (p = 0.120). Dysmenorrhea interference did not predict initial pain severity rating (p = 0.106), final pain severity rating (p = 0.134), or pain tolerance (p = 0.360). A moderation analysis indicated that the relationship between dysmenorrhea severity and initial pain severity rating was not moderated by painexpectations, χ²(1) = 0.412, p = 0.521. Discussion: During an experimentally-induced pain task, dysmenorrhea severity but not interference predicted initial pain severity rating, such that higher levels of dysmenorrhea severity predicted greater initial pain severity rating. This suggests individuals with more severe dysmenorrhea pain may experience greater initial sensitivity to pain and be at risk for increased sensitivity to acute pain and potentially the development of chronic pain. [ABSTRACT FROM AUTHOR]

Facial expressions of pain play an important role in pain diagnostics and social interactions. Given the prominent impact of sex on various aspects of pain, it is not surprising that sex differences have also been explored regarding facial expressions of pain; however, with inconclusive findings. We aim to further investigate sex differences in facial expressions of pain by using a large, combined sample to maximize statistical power. Data from 7 previous studies of our group were merged, combining in total the data of 392 participants (male: 192, female: 200). All participants received phasic heat pain, with intensities being tailored to the individual pain threshold. Pain intensity ratings were assessed, and facial responses were manually analyzed using the Facial Action Coding. To compare facial and subjective responses between sexes, linear mixed-effects models were used, with study ID as a random effect. We found significant sex differences in facial responses, with females showing elevated facial responses to pain, although they received lower physical heat intensities (women had lower pain thresholds). In contrast, pain intensity ratings did not differ between sexes. Additionally, facial and subjective responses to pain were significantly associated across sexes, with females showing slightly stronger associations. Although variations in facial expressions of pain are very large even within each sex, our findings demonstrate that women facially communicate pain more intensively and with a better match to their subjective experience compared with men. This indicates that women might be better in using facial communication of pain in an intensity-discriminative manner. [ABSTRACT FROM AUTHOR]

Substantial interindividual variability characterizes osteoarthritis (OA) pain. Previous findings identify quantitative sensory testing (QST), psychological factors, and health-related quality of life as contributors to OA pain and predictors of treatment outcomes. This exploratory study aimed to explain baseline OA pain intensity and predict OA pain after administration of a nonsteroidal antiinflammatory drug in combination with paracetamol for 3 weeks. The Knee Injury and Osteoarthritis Outcome Score (KOOS) pain score was used to estimate OA pain presentation. One hundred one patients were assessed at baseline and follow-up using QST (pressure pain thresholds and temporal summation of pain [TSP]), symptoms of depression and anxiety, pain catastrophizing scales (PCSs), and health-related quality of life. Linear regression with backward selection identified that PCS significantly explained 34.2% of the variability in baseline KOOS pain, with nonsignificant contributions from TSP. Pain catastrophizing score and TSP predicted 29.3% of follow-up KOOS pain, with nonsignificant contributions from symptoms of anxiety. When assessed separately, PCS was the strongest predictor (32.2% of baseline and 24.1% of follow-up pain), but QST, symptoms of anxiety and depression, PCS, and quality of life also explained some variability in baseline and follow-up kneeOA pain. Further analyses revealed that only TSP and PCS were not mediated by any other included variables, highlighting their role as unique contributors to OA pain presentation. This study emphasizes the importance of embracing a multimodal approach to OA pain and highlights PCS and TSP as major contributors to the baseline OA pain experience and the OA pain experience after OA treatment. [ABSTRACT FROM AUTHOR]

Significant gaps remain in the understanding of the etiology and pathogenesis of fibromyalgia (FM), and the COVID-19 pandemic has introduced even more unknowns. Social factors specific to that period, the viral infection itself, and/or vaccination are additional elements that can complicate the progression of the disease or the response to treatment. Aim: The primary hypothesis to be evaluated in this study is that an acute COVID-19 infection, even when considered recovered, may induce changes in the response to non-pharmacological treatment in FM patients, particularly concerning pain. Results: We included 128 patients diagnosed with FM before the pandemic began. The patients were divided based on their history of acute SARS-CoV-2 infection and COVID-19 vaccination status. All patients followed the same rehabilitation program (cognitive therapy, kinesitherapy). Perceived pain: The non-COVID-19 patient groups showed a statistically significant reduction in pain at the final evaluation compared to patients with a history of acute SARS-CoV-2 infection (p < 0.001). Algometric evaluation: Patients without COVID-19 infection and that were vaccinated exhibited the best improvement in pain threshold, both across evaluation times (p < 0.001) and compared to any of the other three groups studied (p < 0.001). Using the WHYMPI questionnaire, the same group of patients (those not having experienced acute COVID-19 and who were vaccinated) was the only group with a statistically significant improvement in pain severity (p = 0.009). In conclusion, to control and improve FM pain symptoms, in addition to appropriate medication, we propose paying additional attention to the history of acute SARS-CoV-2 infection and the COVID-19 vaccination status. [ABSTRACT FROM AUTHOR]

Background: the aim of this study was to investigate the neurophysiological effect of anti-CGRP monoclonal antibodies on central and peripheral levels in migraine patients. Methods: An observational cohort study in patients with migraine was performed. All subjects underwent Single-Pulse and Paired-Pulse Transcranial Magnetic Stimulation, as well as a Pressure Pain Threshold assessment. The same protocol was repeated three and four months after the first injection of anti-CGRP monoclonal antibodies. Results: A total of 11 patients with a diagnosis of migraine and 11 healthy controls were enrolled. The main findings of this study are the significant effects of anti-CGRP mAb treatment on the TMS parameters of intracortical inhibition and the rise in the resting motor threshold in our group of patients affected by resistant migraine. The clinical effect of therapy on migraine is associated with the increase in short-interval intracortical inhibition (SICI), resting motor threshold (RMT), and Pressure Pain Threshold (PPT). In all patients, all clinical headache parameters improved significantly 3 months after the first injection of mAbs and the improvement was maintained at the 1-month follow-up. At baseline, migraineurs and HCs had significant differences in all TMS parameters and in PPT, while at follow-up assessment, no differences were observed on RMT, SICI, and PPT between the two groups. After anti-CGRP monoclonal antibody injection, a significant increase in the intracortical inhibition, in the motor threshold, and in the Pressure Pain Threshold in critical head areas was observed in patients with migraine, which was related to significant clinical benefits. Conclusions: Anti-CGRP monoclonal antibodies improved clinical and neurophysiological outcomes, reflecting a normalization of cortical excitability and peripheral and central sensitization. By directly acting on the thalamus or hypothalamus and indirectly on the trigeminocervical complex, treatment with anti-CGRP monoclonal antibodies may modulate central sensorimotor excitability and peripheral sensitization pain. [ABSTRACT FROM AUTHOR]

Depression is a growing public health concern, and exercise is an adjunctive treatment modality to improve depression, but the optimal form of exercise and the optimal dose are still unclear. This systematic review examined the efficacy of four major types of exercise (aerobic, resistance, mixed, and mind-body) on depression, as well as the dose-response relationship between total and specific exercise and depressive symptoms. We included randomized controlled trials that included participants aged 18 years or older with a diagnosis of major depressive disorder or a depressive symptom score above a threshold as determined by a validated screening measure, implemented one or more exercise therapy groups, and assessed depressive symptoms at baseline and follow-up. Forty-six studies (3164 patients) were included in the meta-analysis. Aerobic (standardised mean difference (SMD) = -0.93; 95% CI: -1.25 to -0.62) and mind-body exercise (SMD) = -0.81; 95% CI: -1.19 to -0.42) improved depressive symptoms better compared to controls, followed by mixed (SMD = -0.77; 95% CI: -1.20 to -0.34) and resistance exercise (SMD = -0.76; 95% CI: -1.24 to -0.28). This dose-response meta-analysis showed a U-shaped curve between exercise dose and depressive symptoms. The minimum effective dose was estimated to be 320 metabolic equivalent (METs) -min per week and the optimal response was 860 METs-min per week. These findings lead us to advocate that clinicians carefully select the appropriate dose of exercise based on the patient's individual characteristics and needs, in conjunction with psychological care interventions. • Aerobic, resistance, mixed and mind-body exercise interventions have significant and comparable benefits in improving clinical depressive symptoms in patients with MDD. • There was a U-shaped dose-response relationship between overall exercise volume and depression level, with the maximum significant response occurring at 860 METs-min, and a minimal clinically meaningful difference (MCID) in depression improvement with 477 METs-min of exercise per week. [ABSTRACT FROM AUTHOR]

Background: Tension-type headache (TTH) is the most prevalent primary headache. Pressure pain thresholds (PPTs) reflect the pressure pain sensitivity of the tissues. Women with TTH have showed greater pressure hypersensitivity in some muscles compared to men. The aim of this study was to compare the PPTs from myofascial trigger points in cervical and cranial muscles which might contribute to headaches between men and women with TTH. Methods: An observational and correlation cross-sectional study was performed. PPTs were evaluated bilaterally and compared between men and women in the following muscles: upper trapezius, splenius capitis and cervicis, semispinalis, rectus capitis posterior major, obliquus capitis superior and inferior, occipitofrontalis posterior and anterior, temporalis, masseter, clavicular and sternal head of sternocleidomastoid, zygomaticus major, and levator scapulae. The mean PPT was calculated as well. Results: Significant differences showing lower PPTs in women compared to men were found in the mean PPT (p = 0.000) and in all the points except in the left clavicular head of the sternocleidomastoid (p = 0.093) and in the left masseter (p = 0.069). Conclusions: Lower PPTs from myofascial trigger points in cervical and cranial muscles, which might contribute to headaches, were observed in women compared to men with TTH. The mean PPT was also lower in women than in men, suggesting the need for gender-specific approaches in the treatment of TTH. [ABSTRACT FROM AUTHOR]

Background: Central and peripheral sensitization are characterized by widespread hyperalgesia that is manifested by larger pain extent area and reduction in pressure pain threshold (PPT). PPT decreases in patients with migraine not only over the trigeminal cervical complex but also throughout the body. Methods: A cross-sectional study was adopted to assess the local and widespread hyperalgesia in chronic and episodic migraine patients respect to healthy controls. The guidelines of Andersen's were used to evaluate the PPT bilaterally over 3 muscles in the trigemino-cervical complex (temporalis, sub-occipitalis, trapezius) and over 1 muscle far from this area (tensor fasciae latae). Results: Thirty subjects with episodic migraine (35.8 ± 2.82 years), 30 with chronic migraine (53.03 ± 19.79 years), and 30 healthy controls (29.06 ± 14.03 years) were enrolled. The interaction effect was present for the trapezius muscle with a significant difference between the right and the left side in episodic group (p = 0.003). A group effect was highlighted in all four muscles analyzed such as suboccipital (p < 0.001), temporalis (p > 0.001), trapezius (p < 0.001), and TFL (p < 0.001). PPT was usually higher in the control group than in the episodic group which in turn was characterized by higher PPT values than the chronic group. Conclusions: People with chronic and episodic migraine presented lower PPT than healthy controls both in the trigeminal and in the extra-trigeminal area. People with chronic migraine presented lower PPT than episodic migraine only in the trigeminal area. Temporalis and sub-occipitalis are the most sensitive muscles in people with chronic and episodic migraine. [ABSTRACT FROM AUTHOR]

Background: Rheumatoid arthritis is an autoimmune inflammatory disorder that mainly affects bone and cartilage architecture. The continuous use of NSAIDs and DMARDs is associated with severe toxic effects. Therefore, the current study was designed to scrutinize herb-based therapy for the treatment of RA. Aim: To evaluate the anti-arthritic activity of ethanol extract of Ziziphus nummularia using formaldehyde-induced arthritic model in rats and elucidate the possible mechanism for anti-arthritic activity. Materials and methods: Anti-arthritic activity of ETZN was studied at three oral doses, i.e., 200, 400, and 600 mg/kg. Selected doses were studied using various clinical parameters viz. paw volume, inflammatory index, motility test, stair test, anti-nociceptive efficacy, walking track analysis, and motor activity) from day 1 to day 10. On the last day, the animals were killed for the evaluation of hematological parameters, oxidative stress biomarkers, and histological and radiographic studies of the hind paw. Results: Treatment with ETZN 400 mg/kg and 600 mg/kg markedly elicited a significant reduction in paw volume, inflammatory index, and nociceptive action compared to diseased animals. Furthermore, the anti-inflammatory activity was confirmed by increased latency of pain threshold in thermal and mechanical algesia models. The anti-arthritic activity is mainly attributed to a reduction in oxidative stress biomarkers as well as restoration of haematological profile in treated animals when compared to diseased animals. Lastly, the anti-arthritic potential was confirmed by histological and radiological analysis which revealed a marked reduction in inflammatory cells and bone destruction as compared to diseased animals. Conclusion: The study revealed that ETZN exhibits significant anti-arthritic activity via modulation of oxidative stress biomarkers, restoration of hematological profile, and reduction in bone erosion. [ABSTRACT FROM AUTHOR]

Sexual dimorphism among mammals includes variations in the pain threshold. These differences are influenced by hormonal fluctuations in females during the estrous and menstrual cycles of rodents and humans, respectively. These physiological conditions display various phases, including proestrus and diestrus in rodents and follicular and luteal phases in humans, distinctly characterized by varying estrogen levels. In this study, we evaluated the capsaicin responses in male and female mice at different estrous cycle phases, using two murine acute pain models. Our findings indicate that the capsaicin-induced pain threshold was lower in the proestrus phase than in the other three phases in both pain assays. We also found that male mice exhibited a higher pain threshold than females in the proestrus phase, although it was similar to females in the other cycle phases. We also assessed the mRNA and protein levels of TRPV1 in the dorsal root and trigeminal ganglia of mice. Our results showed higher TRPV1 protein levels during proestrus compared to diestrus and male mice. Unexpectedly, we observed that the diestrus phase was associated with higher TRPV1 mRNA levels than those in both proestrus and male mice. These results underscore the hormonal influence on TRPV1 expression regulation and highlight the role of sex steroids in capsaicin-induced pain. [ABSTRACT FROM AUTHOR]

Purpose: To investigate pain hypervigilance in individuals suffering from chronic neck and shoulder pain (CNSP) and its underlying brain mechanism. Methods: The evaluation of pain vigilance was conducted through the utilization of pain vigilance and awareness questionnaires. Voxel-wise regional homogeneity (ReHo) from 60 CNSP patients and 60 healthy controls (HCs) using resting-state fMRI data. Voxel-wise two-sample T-test was conducted to reveal the ReHo variations between CNSP and HC. Correlation analyses were utilized to reveal the connection between brain abnormalities and medical measurements. Furthermore, a mediation analysis was conducted to elucidate the pathway-linking changes in brain function with medical measurements. Results: Our present study revealed three main findings. Firstly, patients with CSNP demonstrated a heightened vigilance of pain in comparison to healthy adults, a common occurrence among individuals with chronic pain conditions. Secondly, we observed brain abnormalities in various brain regions in CSNP patients, and these alterations were associated with the extent of pain vigilance. Lastly, the pain hypervigilance impact on the severity of pain was found to be controlled by regional neural activity in the anterior cingulate cortex (ACC) in subjects with CSNP. Conclusion: Our findings suggested that long-term repetitive nociceptive input caused by chronic pain further aggravates the pain intensity by impairing the vigilance-related pain processing within the anterior cingulate cortex in CNSP patients. [ABSTRACT FROM AUTHOR]

Objectives: Irritability is a foundational clinical reasoning concept in rehabilitation to evaluate reactivity of the examination and treatment. While originally theorized to reflect tissue damage, a large body of evidence supports pain is a biopsychosocial experience impacted by pain sensitivity and psychological factors. Therefore, the purpose of this study was to examine biopsychosocial contributors to irritability. Methods: 40 patients with shoulder (n = 20) and low back (n = 20) pain underwent Quantitative Sensory Testing (QST) (Pressure Pain Threshold, Heat Pain Threshold, Conditioned Pain Modulation, Temporal Summation), completed pain-related psychological questionnaires, an Exercise-Induced Hypoalgesia protocol, and standardized irritability assessment based on Clinical Practice Guidelines. Participants were then categorized as irritable or not irritable based on Maitland's criteria and by irritability level based on Clinical Practice Guidelines. An independent samples t-test examined for differences in QST and psychological factors by irritability category. A MANOVA examined for differences in QST and psychological factors by irritability level (high, moderate, low). Results: Significantly lower heat and pressure pain thresholds at multiple locations (p < 0.05), as well as less efficient conditioned pain modulation (p = 0.02), were demonstrated in individuals categorized as irritable. Heat and pressure pain thresholds were also significantly lower in patients with high irritability compared to other levels. Significantly higher depression and anger, as well as lower self-efficacy, were reported in individuals with an irritable presentation. Discussion/Conclusion: Biopsychosocial factors, including widespread hyperalgesia and elevated psychological factors, may contribute to an irritable presentation. [ABSTRACT FROM AUTHOR]

• Women with Endometriosis and CPP have more musculoskeletal disorders of the PLC than women without Endometriosis. • Women with Endometriosis and CPP have a lower pressure pain threshold than women without Endometriosis. • There is a decrease in the range of motion in the muscles of the PLC of women with Endometriosis compared to healthy women. • There is a higher score in the kinesiophobia questionnaire in the presence of low back pain. • There is a higher index of physical disability in the presence of low back pain. Use clinical pain measurement tools to investigate and compare the prevalence of pelvic loin disoders in women with and without endometriosis. Chronic pelvic pain (CPP) associated with endometriosis has diverse origins, including musculoskeletal factors. Musculoskeletal dysfunction in the pelvic region is theorized to result from sustained muscular contraction, triggered by altered visceral stimuli and adoption of antalgic postures, causing secondary damage to muscles, ligaments, and joints. CPP significantly impacts quality of life, relationships, sexuality, and mental health. However, limited data exists on musculoskeletal impacts of endometriosis and CPP. It was made a case-control study at Maternidade Escola Assis Chateaubriand from August 2017 to January 2021. Evaluated 71 women: 41 in endometriosis group (EG) and 30 in control group (CG). Data collection included sociodemographic questionnaires, musculoskeletal physiotherapeutic evaluations, pain mapping, pressure pain thresholds, kinesiophobia, and disability measurements. Statistical analysis was performed using Spearman's Rho test to determine correlations. Mean age of participants was 31 years. EG exhibited lower pain threshold variations in lumbopelvic trigger points than CG (P <.05). Significant muscle flexibility differences between groups were observed; EG had reduced flexibility (P <.05). Most common pain areas were hypogastrium in EG (48.78 %) and left lumbar in CG (30 %). EG had higher kinesiophobia values (P =.009). There was a weak association between kinesiophobia-pressure threshold association observed in CG's lumbar pelvic region. Women with Endometriosis and CPP exhibit higher prevalence of musculoskeletal disorder, lower pain thresholds, decreased lumbopelvic muscle range of motion, higher kinesiophobia scores, and increased disability indices with low back pain compared to healthy women. [ABSTRACT FROM AUTHOR]

Objective: To compare the immediate effects of shockwave therapy using two different tips in patients with chronic non-specific low back pain. Design: Randomised placebo-controlled study with three intervention groups. Setting: The patients recruited for this study were sent for physiotherapy treatment at primary care between May and July 2022. Participants: Eighty-one patients with chronic non-specific low back pain aged 18–80 years with pain for ≥3 months and pain intensity ≥3 were randomly recruited for the study. Intervention: The patients received a single intervention of radial shockwave therapy with 2000 discharges at 100 mJ energy and 5 Hz frequency using concave or convex tips or placebo treatment. Main measures: The primary outcome was pain intensity immediately post-intervention. The secondary outcomes were pressure pain threshold, temporal summation of pain, and functional performance. Data were collected at baseline and post-intervention. Results: The post-intervention pain intensity in the concave tip group is an average of two points lower (95% CI = −3.6, −0.4; p < 0.01) than that in the placebo group. The post-intervention pressure pain threshold for the concave tip group was an average of 62.8 kPa higher (95% CI = 0.4, 125.1; p < 0.05) than for the convex tip group and 76.4 kPa higher (95% CI = 14, 138.7; p < 0.01) than in the placebo group. Conclusion: The concave tip shockwave therapy is effective in reducing pain and local hyperalgesia in patients with chronic non-specific low back pain. [ABSTRACT FROM AUTHOR]

Wide-range thermoreceptive neurons (WRT-EN) in monkey cortical area 7b that encoded innocuous and nocuous cutaneous thermal and threatening visuosensory stimulation with high fidelity were studied to identify their multisensory integrative response properties. Emphasis was given to characterizing the spatial and temporal effects of threatening visuosensory input on the thermal stimulus-response properties of these multisensory nociceptive neurons. Threatening visuosensory stimulation was most efficacious in modulating thermal evoked responses when presented as a downward ("looming"), spatially congruent, approaching and closely proximal target in relation to the somatosensory receptive field. Both temporal alignment and misalignment of spatially aligned threatening visual and thermal stimulation significantly increased mean discharge frequencies above those evoked by thermal stimulation alone, particularly at near noxious (43°C) and mildly noxious (45°C) temperatures. The enhanced multisensory discharge frequencies were equivalent to the discharge frequency evoked by overtly noxious thermal stimulation alone at 47°C (monkey pain tolerance threshold). A significant increase in behavioral mean escape frequency with shorter escape latency was evoked by multisensory stimulation at near noxious temperature (43°C), which was equivalent to that evoked by noxious stimulation alone (47°C). The remarkable concordance of elevating both neural discharge and escape frequency from a nonnociceptive and prepain level by near noxious thermal stimulation to a nociceptive and pain level by multisensory visual and near noxious thermal stimulation and integration is an elegantly designed defensive neural mechanism that in effect lowers both nociceptive response and pain thresholds to preemptively engage nocifensive behavior and, consequently, avert impending and actual injurious noxious thermal stimulation. NEW & NOTEWORTHY: Multisensory nociceptive neurons in cortical area 7b are engaged in integration of threatening visuosensory and a wide range of innocuous and nocuous somatosensory (thermoreceptive) inputs. The enhancement of neuronal activity and escape behavior in monkey by multisensory integration is consistent and supportive of human psychophysical studies. The spatial features of visuosensory stimulation in peripersonal space in relation to somatic stimulation in personal space are critical to multisensory integration, nociception, nocifensive behavior, and pain. [ABSTRACT FROM AUTHOR]

Background: Psychosocial function of Chinese temporomandibular disorders (TMD) pain patients and the correlation with somatosensory function has not been sufficiently studied. Objective: The study aims at assessing the psychosocial function of Chinese TMD pain patients by visualisation method and evaluating the correlations with somatosensory function quantitatively. Methods: The Symptom Checklist 90 (SCL‐90) questionnaire and standardised quantitative sensory testing (QST) were administered to 70 Chinese TMD pain patients and age‐ and gender‐matched healthy controls (HCs). Of these, 40 TMD arthralgia patients received QST before and after medication. Psychosocial and somatosensory parameters were transformed into standardised scores. Differences within groups were assessed through t tests. Correlations between psychosocial and somatosensory profiles were explored through correlation analyses with Bonferroni correction for multiple comparisons. Results: 100% of the Chinese TMD pain patients exhibited psychosocial distress in contrast to HCs. Anger and hostility showed negative correlation with the thermal nonnociceptive parameter (thermal sensory limen, p =.002) and nociceptive parameters (cold pain threshold and pain pressure threshold, p<.001). Correlation analysis indicated that cold detection threshold was negatively correlated with somatization and mechanical pain sensitivity had a negative correlation with anger and hostility through medical treatment (p <.001). Conclusions: Visual psychosocial profiles provided an easy overview of psychosocial function in Chinese TMD pain patients. Anger and hostility was associated with increased thermal nonnociceptive and nociceptive sensitivity to stimuli. Psychosocial distress might be negatively associated with TMD treatment response which indicated a possible need for psychological intervention during treatment. [ABSTRACT FROM AUTHOR]

Background: Symptomatic irreversible pulpitis often results in heightened reactions to thermal stimuli such as pain evoked by a cold stimulus, and spontaneous odontogenic pain (unprovoked pain). Objective: This study primarily compared the clinical manifestations of odontogenic spontaneous pain and pain provoked by cold stimulus specifically focusing on their sensory discriminative characteristics (intensity, duration and quality) between symptomatic irreversible pulpitis patients with and without referred pain. Methods: Twenty‐three patients with symptomatic irreversible pulpitis with referred pain and 12 patients without referred pain were included in this cross‐sectional study. The following outcomes were assessed: odontogenic spontaneous pain and its descriptors; pain evoked by cold stimulus and qualitative sensory testing before and after local anaesthesia; referred pain location; use of analgesic medication; complementary anaesthesia efficacy. T‐test, chi‐squared and McNemar tests were applied to the data (p <.50). Results: Patients with referred pain presented a greater odontogenic pain intensity (p <.05) when considered the average of the last 24 h. These patients also showed higher pain rating and pain descriptors (p <.05). Intensity and duration of the pain evoked by cold stimulus in the non‐affected contralateral tooth at baseline were higher for patients with referred pain (p <.05). Conclusion: Symptomatic irreversible pulpitis patients with referred pain present greater odontogenic spontaneous pain and a heightened pain sensitivity. Therefore, patients with referred pain seem more complex from a pain severity perspective, supporting the clinical utility of discriminating symptomatic irreversible pulpitis with and without referred pain. [ABSTRACT FROM AUTHOR]

Background: Transcutaneous electrical nerve stimulation (TENS) is a non-invasive modality that utilizes electrical currents to modulate pain in populations with acute and chronic pain. TENS has been demonstrated to produce hypoalgesic effects in postoperative pain, fibromyalgia, knee osteoarthritis, and healthy subjects. Transcutaneous auricular vagus nerve stimulation (TaVNS) is a non-invasive modality that modulates the vagus nerve by stimulating its auricular branches. The effects of the combination of TENS and TaVNS on producing an analgesic response have not been studied. Considering that TENS and TaVNS both stimulate similar analgesic pathways but through different means of activation, we can hypothesize that a combination of both methods can produce a more pronounced analgesic response. Therefore, the objective of this study is to assess the hypoalgesic effect of a combination of TENS and TaVNS in pain-free subjects. Methods/design: The study will be a simple crossover design conducted at the University of Hartford. Subjects will be recruited from the University of Hartford population via oral communication, digital flyers, and posters on campus. Thirty participants will undergo two sessions in a crossover manner with one week in between. During one session, the participants will receive TENS with active TaVNS and the other session will be a placebo procedure (TENS with placebo TaVNS). The order of these sessions will be randomized. Importantly, the pressure pain threshold (PPT) and heat pain threshold (HPT) assessors will be blinded to the treatment category. For active TaVNS, a frequency of 25 Hz will be applied with a pulse duration of 200 µs. For placebo TaVNS, the intensity will be increased to a sensory level and then decreased to 0 mA. High-frequency TENS of 100 Hz will be applied in both sessions, with a pulse duration of 200 µsec, asymmetrical biphasic square waveform, and intensity of maximal tolerance without pain. TENS and TaVNS will be turned on for 30 min after a baseline measurement of outcomes. TENS and TaVNS will then be turned off, but the electrodes will remain on until completion of post-treatment assessment. Pressure pain threshold, heat pain threshold, blood pressure, oxygen saturation, and heart rate will be tested 4 times: Once pre-intervention, once during intervention, once immediately after the intervention, and once 15 min post-intervention. Statistical analysis of the data obtained will consider a significance level of p < 0.05. Discussion: This study will provide evidence concerning the combined effects of TENS and TaVNS on pain threshold in pain-free participants. Based on the outcomes, a greater understanding of how TENS and TaVNS, when used in conjunction, can modulate pain pathways. Trial registration: ClinicalTrials.gov NCT06361381. Registered on 09 April 2024. [ABSTRACT FROM AUTHOR]

Summary Viscosity–vaso‐occlusion (VVO) and haemolysis–endothelial dysfunction (HED) are pathophysiological mechanisms and clinical subphenotypes of sickle cell disease (SCD). Recurrent vaso‐occlusive crises (VOC) may lead to neuroplastic changes and pain sensitization. Among 257 SCD participants, we assessed the relationship of subphenotypes with pain sensitivity using quantitative sensory testing to identify heat pain thresholds (HPT) and pressure pain thresholds (PPT). VOC history and sleep, social and emotional functioning were assessed using the adult sickle cell quality of life measurement information system. The ‘elbow method’ determined the optimal number of clusters as three. Clustering was performed using K‐prototypes. Among clusters 2 and 3, VOC frequency and severity were higher. Clusters 1 and 3 had lower haemoglobin, higher reticulocytes and lactate dehydrogenase and more leg ulcers. In multivariate regression, cluster 3 was associated with approximately 13.6% lower PPT compared to cluster 1, and female sex was associated with decreases in PPT and HPT at the hands and feet (p < 0.001). Hydroxyurea use and unit increases in sleep functioning and age were associated with approximately 20.1% higher foot‐PPT, 6.8% higher hand‐PPT and 2.5% higher hand‐HPT and foot‐HPT respectively. Findings suggest that a third subphenotype with mixed VVO and HED features and worse pain sensitization may exist. [ABSTRACT FROM AUTHOR]

IntroductionMethodsResultsConclusionsSmall fibre neuropathy (SFN) is an early manifestation of diabetic polyneuropathy. Although oxidative stress, inflammation and change of intestinal bacterial population are assumed to be their pathogenesis, the effects of dietary nutrition have not been evaluated. The relationship between dietary nutrition intake and pain sensation was evaluated in the Japanese population.We conducted the Iwaki project, a population-based study recruiting 1,028 individuals, in 2018. The relationships between the pain threshold from intraepidermal electrical stimulation (PINT) and the amount of dietary nutrition evaluated by a brief-type self-administered diet history questionnaire were examined. The odds ratio was further explored after categorizing subjects based on low (< 63.7 μg/day), intermediate (63.7-159.2 μg/day), and high cryptoxanthin levels (> 159.2 μg/day).Univariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake even after adjustments for other nutritional intakes (ß = 0.107, p < 0.01). Multivariate logistic regression analysis revealed low and high cryptoxanthin intake as significant risk factors for abnormal PINT (≥ 0.20 mA). Multivariate linear regression analyses showed significant correlations between PINT and cryptoxanthin intake levels after adjustment for other clinically PINT-related factors (ß = 0.09, p < 0.01).Adequate intake of cryptoxanthin is recommended to maintain the pain threshold in the Japanese population. [ABSTRACT FROM AUTHOR]

Background: Quantitative sensory tests (QST) are frequently used to explore alterations in somatosensory systems. Static and dynamic QST like pain threshold and temporal summation (TS) and conditioned pain modulation (CPM) are commonly used to evaluate excitatory and inhibitory mechanisms involved in pain processing. The aim of the present study was to document the reliability and the minimal detectable change (MDC) of these dynamic QST measurements using a standardized experimental paradigm. Material and methods: Forty-six (46) pain-free participants took part in 2 identical sessions to collect TS and CPM outcomes. Mechanical (pressure pain threshold [PPT]) and thermal (constant 2-minute heat pain stimulation [HPS]) nociceptive stimuli were applied as test stimuli, before and after a cold-water bath (conditioning stimulus). TS was interpreted as the change in pain perception scores during HPS. CPM were determined by calculating the difference in pain perception between pre- and post- water bath for both PPT and HPS. Relative and absolute reliability were analyzed with intra-class correlation coefficient (ICC2, k), standard error of the measurements (SEMeas) and MDC. Results: Results revealed a good to excellent relative reliability for static QST (ICC ≥ 0.73). For TS, a poor to moderate relative reliability depending on the calculation methods (ICC = 0.25 ≤ ICC ≤ 0.59), and a poor relative reliability for CPM (ICC = 0.16 ≤ ICC ≤ 0.37), both when measured with mechanical stimulation (PPT) and thermal stimulation (HPS). Absolute reliability varied from 0.73 to 7.74 for static QST, 11 to 22 points for TS and corresponded to 11.42 points and 1.56 points for thermal and mechanical-induced CPM, respectively. MDC analyses revealed that a change of 1.58 to 21.46 point for static QST, 31 to 52 points for TS and 4 to 31 points for CPM is necessary to be interpreted as a real change. Conclusion: Our approach seems well-suited to clinical use. Although our method shows equivalent relative and absolute reliability compared to other protocols, we found that the reliability of endogenous pain modulation mechanisms is vulnerable, probably due to its dynamic nature. [ABSTRACT FROM AUTHOR]

While interactive distractors are predicted to be more effective in reducing acute pain than passive distractors, the underlying mechanisms remain poorly understood. Previous work using Virtual-Reality (VR) has suggested that interactive distraction may be enhanced by increasing the person’s sense of immersion. Despite the possible utility of immersive VR in reducing pain, some people report being disoriented and motion sick, and it doesn’t allow for interactions with environment (e.g., following instructions from medical staff). Here, we explore the role of the immersion in the effectiveness of interactive distraction by employing an alternative technology, a Mixed-Reality (MR) headset that limits disorientation by projecting virtual objects into the real world. Healthy volunteers (18–35 years) participated in two experiments employing either a between (N = 84) or a within-subject (N = 42) design to compare Interactive and Passive distraction tasks presented via MR or a standard computer display. For both experiments, a cold-pressor task was used to elicit pain, with pain tolerance and pain perception being recorded. Analysis revealed that whilst interactive distraction was more effective in reducing pain perception and increasing pain tolerance than passive distraction, the interpretation of results was sensitive to experimental design. Comparison of devices did not reveal significant differences in pain tolerance or pain intensity, while pain unpleasantness was significantly reduced during the MR task using a withinsubject design. Our findings add to existing VR studies reporting little additional analgesic benefit of new, immersive technologies compared to traditional computers, but underscores the important impact the choice of experimental design can have on the interpretation of results. [ABSTRACT FROM AUTHOR]

Introduction: The aim of the present study was to determine the effectiveness of simultaneous bilateral visual diaphragm biofeedback (BFB) from ultrasonography in conjunction with inspiratory muscle training (IMT) on diaphragmatic thickness during normal breathing and respiratory and clinical outcomes in patients with non-specific low back pain (NSLBP) and determine the influence of age and sex. Methods: A single-blind randomized clinical trial was carried out (NCT04582812). A total sample of 96 patients with NSLBP was recruited and randomized by sexbased stratification into IMT (n = 48) and BFB + IMT (n = 48) interventions over 8 weeks. Bilateral diaphragmatic thickness at maximum inspiration (Tins) and expiration (Texp), respiratory pressures, lung function, pain intensity, bilateral pressure pain threshold (PPT), disability, and quality of life were measured at baseline and after 8 weeks. Results: The BFB + IMT group showed significant differences (p < 0.05) with increased left hemidiaphragm thickness at Tins and Tins-exp (d = 0.38-053), and right and left PPT (d = 0.71-0.74) versus the IMT group. The interaction with sex was statistically significant (p = 0.007; F(1,81) = 7.756; ηp 2 = 0.087) and higher left hemidiaphragm thickness at Tins was predicted by the BFB + IMT group (R² = 0.099; β = 0.050; F(1,82) = 8.997; p = 0.004) and male sex (R2 = 0.079; β = 0.045; F(1,81) = 7.756;p = 0.007). Furthermore, greater left hemidiaphragm thickness at Tins-exp was predicted by younger age (R² = 0.052; β = -0.001; F(1,82) = 4.540; p = 0.036). Discussion: The simultaneous bilateral visual diaphragm biofeedback by ultrasonography in conjunction with IMT was effective in both increasing the left diaphragmatic thickness during inspiration, which was positively influenced and predicted by male sex and younger age, and increasing the bilateral PPT of the paraspinal muscles in patients with NSLBP. [ABSTRACT FROM AUTHOR]

Coix seed is a nutrient-rich food and traditional Chinese medicine with anti-inflammatory and analgesic properties. Polysaccharides from Coix seed have been rarely investigated for structure and activities. In this study, the analgesic and anti-inflammatory effects were investigated in vivo and in vitro. The results showed that Coix seed had a significant influence on reducing the number of writhing, increasing the pain threshold and alleviating the swelling degree caused by acute inflammation. Column chromatography was used to obtain two active compounds of Coix seed. Compound 1 was (1→6)-α-glucan with a molecular weight of 6.81 × 105 Da. The chemical connection of compound 2 was as follows: α-Frup (2→ [1)-α-Glcp (6]5→1)-α-Glcp (4→1)-α-Glcp, which was isolated in Coix seed for the first time. LPS-induced inflammation in RAW264.7 cells was well inhibited by compounds. These findings offered a preliminary investigation into the analgesic and anti-inflammatory properties of Coix seed, which may be helpful for application. [ABSTRACT FROM AUTHOR]