Search Results (270)

Pain following orthodontic treatment is the chief complaint of patients undergoing this form of treatment. Although the use of diode lasers has been suggested for pain reduction, the mechanism of laser-induced analgesic effects remains unclear. Neuropeptides, such as substance P (SP) and calcitonin gene-related peptide (CGRP), contribute to the transmission and maintenance of inflammatory pain. Heat shock protein (HSP) 70 plays a protective role against various stresses, including orthodontic forces. This study aimed to examine the effects of diode laser irradiation on neuropeptides and HSP 70 expression in periodontal tissues induced by experimental tooth movement (ETM). For inducing ETM for 24 h, 50 g of orthodontic force was applied using a nickel–titanium closed-coil spring to the upper left first molar and the incisors of 20 male Sprague Dawley rats (7 weeks old). The right side without ETM treatment was considered the untreated control group. In 10 rats, diode laser irradiation was performed on the buccal and palatal sides of the first molar for 90 s with a total energy of 100.8 J/cm². A near-infrared (NIR) laser with a 808 nm wavelength, 7 W peak power, 560 W average power, and 20 ms pulse width was used for the experiment. We measured the number of facial groomings and vacuous chewing movements (VCMs) in the ETM and ETM + laser groups. Immunohistochemical staining of the periodontal tissue with SP, CGRP, and HSP 70 was performed. The number of facial grooming and VCM periods significantly decreased in the ETM + laser group compared to the ETM group. Moreover, the ETM + laser group demonstrated significant suppression of SP, CGRP, and HSP 70 expression. These results suggest that the diode laser demonstrated analgesic effects on ETM-induced pain by inhibiting SP and CGRP expression, and decreased HSP 70 expression shows alleviation of cell damage. Thus, although further validation is warranted for human applications, an NIR diode laser can be used for reducing pain and neuropeptide markers during orthodontic tooth movement. Full article

Background: Inflammation abrogates cellular organization and tissue homoeostasis, resulting in redness, swelling, heat, pain, and loss of function. A model of carrageenan-induced paw edema (CIE) is commonly utilized to test anti-inflammatory substances. Based on the ability of Lepisanthes alata (LA), a tropical plant that is rich in phytochemicals like polyphenols, this study assessed the optimal dose and the health benefits of LA in rats that had been induced with carrageenan to develop paw swelling. Methods: Twenty-four male Wistar rats were divided into four groups to which carrageenan was administered, after which, distilled water at oral dose (C + DW), sodium diclofenac 25 mg/kg (C + DS), LA extract in 250 mg/kg (C + LA250), and 500 mg/kg (C + LA500) was given, respectively. Paw edema was assessed in 24 h. Pain was assessed using the Rat Grimace Scale (RGS), cytokines, antioxidant activity, and tissue changes. Results: LA at 250 and 500 mg/kg significantly decreased paw edema and inflammatory markers in the results of both studies. Remarkably, LA 250 mg/kg significantly decreased RGS scores as well as IL-1β, TNF-α, and histological inflammation but had a positive effect on T-SOD levels. Conclusions: LA extract, especially at 250 mg/kg, shows potent anti-inflammatory, analgesic, and antioxidant properties in CIE rats. Full article

Background: Heat therapy (HT) and electroacupuncture (EA) are widely utilized pain relief methods, but the analgesic mechanisms of their combined application remain unclear. Methods: In acetic acid (AA)-induced writhing test and complete Freund’s adjuvant (CFA)-induced inflammatory pain tests, mice received one of three treatments: EA at bilateral ST36, HT via a 45 °C heating pad, or the combination (EA + HT). To probe underlying pathways, separate groups were pretreated with caffeine, DPCPX (a selective adenosine A₁ receptor antagonist), or naloxone (an opioid receptor antagonist). Spinal expression of glial fibrillary acidic protein (GFAP) and phosphorylated p38 (p-p38) was examined by Western blot and immunofluorescence. Results: Both EA and HT individually reduced AA-induced writhing, with the combination (EA + HT) exhibiting the greatest analgesic effect. EA’s analgesic effect was reversed by caffeine and DPCPX and partially by naloxone, while HT’s effect was reversed by caffeine and DPCPX but was unaffected by naloxone. AA injection elevated spinal p-p38 and GFAP expression, which were attenuated by either EA or HT, with the most substantial suppression observed in the EA + HT group. In the CFA model, both treatments alleviated mechanical allodynia, while the combined treatment resulted in significantly greater analgesia compared to either treatment alone. Conclusions: EA combined with HT synergistically enhances analgesia in both AA and CFA pain models, accompanied by reduced spinal inflammation and astrocyte activation. EA’s analgesic effects appear to involve adenosine A₁ receptor pathways and, to a lesser extent, opioid receptor mechanisms, whereas HT’s effects involve adenosine A₁ receptor pathways. Full article

Background and Objective: Intervertebral disc degeneration (IVDD) is a leading cause of lower back pain with limited regenerative treatments. Among emerging regenerative approaches, growth factor-based therapies, such as recombinant human transforming growth factor-beta (Rh-TGF-β), have shown potential for disc regeneration but are hindered by rapid degradation and uncontrolled release by direct administration. Additionally, mechanical stress elevates heat shock protein 90 (HSP-90), impairing cell function and extracellular matrix (ECM) production. This study aimed to investigate a dual self-cross-linked alginate di-aldehyde (ADA) hydrogel system for the sustained delivery of Rh-TGF-β and epigallocatechin gallate (EGCG) to enhance protein stability, regulate release, and promote disc regeneration by targeting both regenerative and stress-response pathways. Methods: ELISA and UV-Vis spectrophotometry assessed Rh-TGF-β and EGCG release profiles. A rat tail IVDD model was established with an Ilizarov-type external fixator for loading, followed by hydrogel treatment with or without bioactive agents. Disc height, tissue structure, and protein expression were evaluated via radiography, histological staining, immunohistochemistry, and Western blotting. Results: The hydrogel demonstrated a biphasic release profile with 100% Rh-TGF-β released over 60 days and complete EGCG release achieved within 15 days. Treated groups showed improved disc height, structural integrity, and proteoglycan retention revealed by histological analysis and elevated HSP-90 expression by immunohistochemistry. In contrast, Western blot analysis confirmed that EGCG effectively downregulated HSP-90 expression, suggesting a reduction in mechanical stress-induced degeneration. Conclusions: ADA hydrogel effectively delivers therapeutic agents, offering a promising strategy for IVDD treatment. Full article

Pulsed radiofrequency (PRF) current applied to peripheral nerves is a modality used in interventional pain medicine, but its underlying mechanisms remain unclear. This study aimed to investigate whether ex vivo exposure of human monocytic THP-1 cells to PRF current or to heat induces β-endorphin production. Methods: THP-1 cells were exposed to PRF current for 15 min or incubated at elevated temperatures (42 °C to 50 °C) for 3 or 15 min. Flow cytometry was used to assess cell viability, and β-endorphin concentrations in culture supernatants were quantified by ELISA. In a separate experiment, cells were stimulated with lipopolysaccharide (LPS) to compare its effects on β-endorphin release. Results: A 3 min exposure to temperatures ≥ 46 °C reduced THP-1 cell viability, whereas a 15 min exposure to PRF current or to heat at 42 °C did not impair viability. Both PRF current and mild heat significantly enhanced β-endorphin release. β-Endorphin levels in the supernatant of LPS-stimulated cells were comparable to those of cells exposed to PRF current. Conclusions: Ex vivo application of PRF current or mild heat enhanced β-endorphin production from THP-1 cells without significant cytotoxicity. These preliminary findings warrant further investigation using primary human monocytes and in vivo models to assess therapeutic potential. Full article

Scorpion envenomation is a public health issue in tropical and subtropical regions. Currently, there is limited data on the biological effects of Hottentotta judaicus scorpion venom (HjSV) in mammals. This study aims to analyze the effect of HjSV on lipopolysaccharide (LPS)-induced hyperalgesia in mice and its potential modulation of the immunological inflammatory response. Hyperalgesia is characterized by an increased response to pain, accompanied by heightened sensitivity that ranges from mild discomfort to intense pain. A series of tests were conducted, including heat resistance testing in BALB/c mice injected subcutaneously with LPS to induce hyperalgesia and intraperitoneally with HjSV. The hot plate test, used to assess pain endurance in mice, showed that LPS-injected mice, particularly females, exhibited heightened pain sensitivity. This suggests possible sex-based differences in pain perception. When HjSV was administered alone, a reduction in pain sensitivity was observed in both sexes. Additionally, ELISA tests were performed to assess changes in the secretion of inflammatory cytokines IL-4, IL-10, IL-6, IFN-γ, and TNF-α. A consistent increase in both pro- and anti-inflammatory cytokines was observed at early time points in females injected with HjSV alone. Moreover, the hyperalgesia induced by LPS was significantly reduced when HjSV was co-administered, indicating an anti-inflammatory effect at early stages. These findings suggest that HjSV has a significant immunomodulatory effect, potentially exerting anti-inflammatory action during acute inflammation. This effect appears to be time-dependent, diminishing as the immune response transitions toward its adaptive phase. Full article

Background/Objectives: Fibromyalgia (FM) is a chronic pain condition that includes symptoms of hyperalgesia and has an unknown etiology. This study aimed to further investigate the underlying neural signaling mechanisms and their relation to observed blood oxygenation-level dependent (BOLD) signal increases at the onset of functional magnetic resonance imaging (fMRI) runs. Methods: The possible neural mechanisms were first explored by reviewing the current literature. The second component of this study involved a voxel-by-voxel analysis of BOLD responses in all regions of the brain. The fMRI data were obtained from a previous study of participants with and without fibromyalgia during fMRI runs involving either a noxious heat pain stimulus or no stimulus. Results: The literature review indicates that no single factor can explain the initial BOLD signal rise observed in FM but that there are likely multiple interacting influences. These include physiological dysregulation via mechanisms, such as oxidative stress, mitochondrial dysfunction, and cytokine activity, and may involve the sympathetic nervous system. The analysis of BOLD responses demonstrated that the initial BOLD rises occur specifically in gray matter regions and are largest in regions involved with pain processing, including the right insular cortex and periaqueductal gray region. Moreover, the BOLD rise is significantly larger in people with FM prior to the application of a noxious stimulus. Conclusions: The initial rise in BOLD response demonstrates heightened metabolic demand that is exaggerated in people with FM. It appears to be influenced by cognitive factors such as anticipation and may reflect neural dysregulation, possibly involving autonomic signaling. Full article

Background/Objectives: Rates of depression, anxiety, sleep disturbances, and chronic pain are higher in people with spinal cord injury (SCI) compared with able-bodied individuals. Passive heat therapy (PHT), which raises core body temperature, may be an accessible therapeutic intervention. The effects of PHT on mental health, sleep, and pain in persons with SCI are unknown. Methods: We performed a time-controlled pre–post intervention pilot study in which ten veterans with chronic SCI underwent an 8-week supervised PHT intervention to raise oral temperature by 1 °C each session. Outcome measures were the 5-item Mental Health Inventory, Epworth Sleepiness Scale, and International Spinal Cord Injury Pain Extended Data Sets version 1.0. Results: There were no adverse events related to the intervention and nine out of ten participants completed all their intervention sessions. There was a reduction in pain intensity (p = 0.039) upon completing the intervention (from a median (IQR) of 2.0 (0.0, 3.5) to 1.0 (0.0, 4.5) on a 0–10 scale). However, there were no improvements in self-reported mental health or sleep outcomes (p > 0.339). Conclusions: This pilot study suggests that supervised repeated passive heat therapy may confer benefits for chronic pain in veterans with chronic SCI. Follow-up studies with larger sample sizes and more extensive sets of chronic pain outcomes are needed to confirm these findings. Full article

Pain assessment is a challenging task for clinicians due to its subjective nature, particularly in individuals with communication difficulties, cognitive impairments, or severe disabilities. Traditional methods such as the Visual Analogue Scale (VAS), Numerical Rating Scale (NRS), and Verbal Rating Scale (VRS) rely heavily on patient feedback, which can be inconsistent and subjective. To address these limitations, developing objective and reliable pain assessment tools that incorporate advanced technologies, such as multimodal data integration from video and fNIRS, is important for improving clinical outcomes. However, challenges such as noise susceptibility in fNIRS signals must be carefully addressed to realize their full potential. Recent studies have explored automatic pain assessment using machine learning and deep learning techniques, which require high-quality data that can accurately represent pain categories. In response to the introduction of a new dataset in the AI4Pain Challenge, we proposed a multimodal neural network model utilizing attention-based fusion to improve overall accuracy (MMAPA). Our model leverages video and fNIRS modalities as well as manually extracted statistical features. We also implemented fNIRS signal preprocessing and artifact noise filtering, which significantly improved performance on both the fNIRS and statistical feature branches. On the hidden test set, our model achieved an accuracy of 51.33%, outperforming the official baseline of 43.33%. To evaluate generalizability, we further tested our method on the BioVid Heat Pain Database, where our fusion model achieved the highest accuracy in the 10-fold cross-validation setting, outperforming PainAttNet and unimodal variants. These results highlight the effectiveness of our multimodal attention-based approach in improving pain classification performance across datasets. Full article

Musculoskeletal disorders represent one of the most pervasive health concerns that drive frequent medical consultations and pharmacy encounters. Community pharmacies are well placed to help address this demand as they are accessible settings for healthcare advice and support for patients with musculoskeletal disorders complaining of pain. Heat therapy stands as a valuable component of a multimodal approach to the management of musculoskeletal pain by virtue of multiple effects: pain relief, reduction of muscle spasms and stiffness, and enhanced muscle flexibility and range of motion. However, there is limited guidance on heat therapy use in routine practice, particularly on indications and contraindications, mode of application, and precautions. Such an educational gap has been documented among pharmacists. Therefore, it is paramount that pharmacists gain knowledge about when and how to effectively integrate superficial heat therapy with both pharmacological and physical therapy, to provide patients with a comprehensive, multimodal approach to alleviating musculoskeletal pain. A multidisciplinary panel of experts gathered to develop practical guidance on heat therapy-appropriate application in patients with musculoskeletal pain. In this work, we provide actionable suggestions to build pharmacists’ competency in managing musculoskeletal pain and empower them in effectively using heat therapy as a single therapeutic option or in combination with over-the-counter analgesics. Full article

Background: A large number of patients suffer from neuropathic pain, and systemic therapy often remains ineffective while inducing severe side effects. Topical therapy with the TRPV1-agonist capsaicin is an established alternative, and the identification of co-therapeutics that modulate TRPV1 may be a promising approach to reduce the dose of capsaicin while maintaining efficacy. Here, we aimed to determine if the antidepressant amitriptyline displays properties rendering it a potential co-therapeutic agent. Methods: We performed patch clamp and calcium imaging experiments on HEK293T cells expressing human (h) TRPV1 as well as on dorsal root ganglion (DRG) neurons from adult mice. Results: Amitriptyline induced an increase in intracellular calcium in both HEK293T and mouse DRG neurons expressing TRPV1. Patch clamp experiments revealed a concentration-dependent activation of hTRPV1 by amitriptyline that was also evident in cell-free inside-out patches. When hTRPV1 was fully activated by capsaicin, amitriptyline induced concentration-dependent and partly reversible current inhibition. In contrast, amitriptyline potentiated small responses to capsaicin, heat and protons. We also found that amitriptyline desensitized hTRPV1 to capsaicin. This effect was reduced by the intracellular application of the strong calcium chelator BAPTA. Furthermore, the non-desensitizing mutant hTRPV1-Y672K displayed a reduced amitriptyline-induced desensitization. Conclusions: Our data showed that amitriptyline can activate, sensitize, desensitize and even inhibit TRPV1. Together with its property as a strong local anesthetic, our data suggest that amitriptyline may be a promising adjunct to topical capsaicin. Full article

Background/Objectives: The repetitive overhead throwing of baseball stresses the posterior shoulder, including the rotator cuff and capsule, causing stiffness, tissue thickening, and dysfunction. Previous studies on collegiate baseball players have linked these changes to glenohumeral internal rotation deficits, pain, and injuries. However, these studies primarily used acoustic radiation force impulse-based shear wave elastography (SWE), which has limitations, including tissue heating and lack of portability. The acute effects of pitching on infraspinatus (ISP) muscle elasticity in high school pitchers remain unclear. Therefore, this study aimed to evaluate the acute impact of pitching on ISP muscle elasticity in high school baseball pitchers using continuous SWE (C-SWE), which is a safer and more portable method. The relationship between ISP muscle elasticity and pitching load was also examined. Methods: ISP muscle shear wave velocity (SWV), shoulder range of motion, and strength were evaluated in high school baseball pitchers. The participants were categorized into pitching and non-pitching groups based on whether they pitched with full effort on the day of their medical checkup. C-SWE was used to assess ISP muscle elasticity. Results: The pitching group had considerably higher ISP muscle SWV on the dominant side than the non-pitching group (p = 0.008). A significant positive correlation was observed between pitch and ISP muscle SWV (r = 0.467, p = 0.003). Conclusions: Repetitive pitching acutely increases ISP muscle stiffness in high school pitchers, contributing to posterior shoulder tightness. C-SWE is a safe and practical method for assessing tissue elasticity and developing injury prevention strategies. Full article

Hemophilic arthropathy (HA) is a complication of hemophilia, which is a genetic disorder characterized by a deficiency in blood clotting factors. HA is characterized by joint damage with inflammatory responses, pain, and movement limitations due to recurrent bleeding in the joints. The inflammatory reactions contribute to the activation of coagulation factors, which can exacerbate bleeding and further damage the affected joints. Therefore, the interaction between inflammation and coagulation plays a crucial role in the progression and complications of HA. Management strategies often focus both on inflammation and coagulation to alleviate symptoms and preserve joint function. Temperature can influence the inflammatory response and coagulation. The aim of this work was to understand how temperature management can positively or negatively influence the HA. We have carried out a narrative review of the available literature. This review explores the impacts of temperature on biological processes, and it discusses the possible clinical implications for the HA treatment. Our research shows that cold exposure has anti-inflammatory and analgesic effects, while heat is linked to pro-inflammatory cytokine release. Both hot and cold treatments are ill-advised for hemophilia patients. Heat stimulates neo-angiogenesis, and cold hampers coagulation, posing risks for increased bleeding in individuals with hemophilia. Full article

Background/Objectives: Wildland firefighters (WFFs) are subjected to significant physical and physiological demands that expose them to substantial occupational risks, including thermal stress, prolonged physical exertion, and exposure to harmful substances. These factors not only affect their immediate performance but also have long-term implications for their health. This narrative review seeks to analyze the main factors influencing the health and performance of WFFs, with a particular focus on physical, environmental, and psychological challenges. Methods: A narrative review was performed, synthesizing data from diverse sources. The analysis centered on studies addressing the physiological, environmental, and psychological aspects of WFF performance. Specific topics included physical workload, exposure to environmental stressors, use of protective equipment, hydration, sleep patterns, and mental health. Results: The review highlights several critical challenges faced by WFFs, including the extreme physical demands of carrying heavy equipment during extended interventions, elevated physiological strain induced by protective gear, and significant health risks associated with smoke inhalation and dehydration. Additionally, inadequate sleep and heightened mental stress were found to impair both cognitive and physical performance. Variations in injury prevalence and patterns of chronic pain were observed, often influenced by factors such as sex, age, and professional experience. Conclusion: To mitigate these risks and enhance the health and performance of WFFs, targeted interventions are essential. These include tailored physical training programs, heat acclimatization strategies, and improved resource management. Future research should aim to integrate these measures comprehensively and address existing knowledge gaps to ensure the long-term well-being of these professionals. Full article

Osteoarthritis (OA), caused by the long-term use of joints, is a representative degenerative disease in the elderly. However, recently, the age of onset has been decreasing owing to excessive activities among young people in their 20s and 30s. Gynostemma pentaphyllum (Thunb.) Makino (GP), a perennial herb of the Cucurbitaceae family, has been used since the Ming dynasty as a medicinal material to treat various ailments, such as rheumatism, liver disease, and diabetes. In this study, we investigated the anti-arthritic effects of heat-processed Gynostemma pentaphyllum extract (Actiponin (AP)) and its derivatives, damulin A (DA) and damulin B (DB), using in vitro (primary rat chondrocytes and SW1353 cells) and in vivo (destabilization of the medial meniscus (DMM)-induced OA model) systems. Histological analysis results from the in vivo study showed that the group that underwent DMM surgery induced degeneration by the loss of proteoglycan and the destruction of cartilage (OARSI score 14 ± 0.57), whereas the group that received AP daily for 8 weeks maintained an intact condition (OARSI score 5 ± 0.28 at 200 mg/kg, p < 0.001). In addition, cartilage thickness and chondrocytes were reduced in the DMM group, but were restored in the AP-administered group. Furthermore, the von Frey analysis results showed that the pain threshold of the DMM group was considerably low (54.5 g at 8 weeks), whereas that of the AP group was dose-dependently increased (65.5, 69.5, 70.3, and 71.8 at 8 weeks for 30, 50, 100, and 200 mg/kg, respectively). In vitro studies showed that AP, DA, and DB reduced the expression of interleukin-1β alone-induced nitrite; inducible nitric oxide synthase; cyclooxygenase-2; matrix metallopeptidase 1/3/13; and a disintegrin and metalloproteinase with thrombospondin motifs 4/5. They also restored the expression of collagen type II and aggrecan, which are components of the extracellular matrix. The anti-arthritic effects of AP, DA, and DB were confirmed to be mediated by the mitogen-activated protein kinase and nuclear factor kappa-light-chain-enhancer of activated B cell signaling pathways. Collectively, these results suggest that AP is a potential therapeutic agent for mitigating OA progression and chondroprotection. Full article