Search Results (325)

Background/Objectives: Chemotherapy-induced neuropathic pain (CINP) represents a critical challenge in oncology, emerging as a common and debilitating side effect of widely used chemotherapeutic agents, such as paclitaxel (PTX). Current therapeutic interventions and preventive strategies for CINP are largely insufficient, as they fail to address the underlying peripheral nerve damage, highlighting an urgent need for the development of new drugs. This study aimed to investigate the dual-function effects on normal cell protection and tumor suppression of BMX-001, a redox-active manganese metalloporphyrin that has demonstrated antioxidant and anti-inflammatory properties, which offers potential in protecting central nervous system tissues and treating CINP. Methods: This study assessed BMX-001’s different roles in protecting normal cells while acting as a pro-oxidant and pro-inflammatory molecule in cancer cells in vitro. We also evaluated its neuroprotective effect in preclinical PTX-induced CINP models in vivo. Results: Our results showed significant reductions in mechanical and cold allodynia, decreased pro-inflammatory cytokine levels, and restored antioxidant capacity in peripheral nerves and dorsal root ganglia (DRGs) following BMX-001 treatment. Conclusions: Overall, our study highlights the therapeutic potential of BMX-001 to mitigate CINP and enhance anticancer efficiency. Its dual-selective mechanism supports the future clinical investigation of BMX-001 as a novel adjunct to chemotherapeutic regimens. Full article

Objective: The aim of this study was to assess the effects of vestibular stimulation (semicircular canals/utricles) compared to cochlear stimulation on phantom pain and depersonalization/derealization symptoms after ≥3 months since traumatic amputation of hand-finger(s). Methods: A total of 125 adults (38.2 ± 8.1 years old) with phantom pain after amputation of one to four fingers agreed to participate. None of them wore prosthetic devices or had history of otology/audiology/vestibular/neurology/rheumatology/orthopedic/psychiatry disorders or psychopharmacological treatment. After a preliminary assessment, in a random order, they were exposed to caloric stimulation (right/left 44 °C/30 °C), centrifuge (right/left), and transient evoked otoacoustic emissions (TOAEs, right/left) with a follow-up of three days in between. Immediately before and after each stimulus, they reported on their pain characteristics and depersonalization/derealization symptoms. Results: After vestibular stimulation, a decrease in pain intensity was reported by at least one-third of the participants, which persisted for at least one day in the majority of them. Less than one-sixth of the participants reported pain decrease after cochlear stimulation. No influence was observed based on the side of the stimulation or the temperature, but the stimuli sequence had an effect. The centrifuge and TOAE effects were related to anxiety/depression symptoms and mainly observed when they were the first stimulus used. After caloric stimulation, pain decrease was independent from the sequence of the stimuli, and it was related to reports of feeling estrangement from the body. Conclusions: Mild caloric vestibular stimulation, whether applied to the right or left side and using warm or cold temperature, can modulate phantom pain after amputation of hand-finger(s) in patients with altered bodily sensations. However, individual cofactors may influence one’s susceptibility to experiencing this effect. Full article

Background: Effective pain management in children is essential, particularly when administering local anaesthesia. This study was undertaken to compare pain perception in children after application of pre-cooled and plain topical anaesthetic gel during local anaesthetic administration. Methods: A randomised, single-blinded controlled trial was conducted among 51 children between the ages of 6 and 12, visiting the paediatric clinic, Jazan (REC-45/10/1070). Children were allocated into one of the following three groups using a simple randomisation having a 1:1:1 allocation ratio into Group I (n = 17): Plain topical anaesthetic gel, Group II (n = 17): Pre-Cooled topical anaesthetic gel, and Group III (n = 17). An ice pack was applied for a period of 1 min at the injection site. The intensity of pain and the behaviour of the children were assessed using Face, Leg, Activity, Cry, Consolability (FLACC), the Modified Wong–Baker Scale (WBS) and the Frankel Behaviour Rating Scale (FBRS). Results: A significant difference in FBRS scores was observed during anaesthesia, with the highest median score [3 (3,3)] in the pre-cooled topical anaesthetic gel group (p value < 0.001). FLACC scores varied significantly among groups, with the ice pack group [3 (3, 3)] and [4 (4, 5)] showing the highest median score (p value < 0.001). WBS scores also differed significantly between groups (p value < 0.001) with a lower value in the pre-cooled topical gel group [0 (0, 0), 2 (0, 2)]. Conclusions: This study concluded that, the use of a pre-cooled topical anaesthetic gel before LA administration reduced the pain better than that of plain anaesthetic gel and ice pack application at the injection site during infiltration. Full article

Background and Objectives: Chronic pain is a significant global health issue, with conventional treatment strategies often proving insufficient or causing undesirable side effects. Interventional pain management techniques, including neuromodulation, have gained increasing interest as alternative therapeutic options. Cryoneurolysis, a technique leveraging extreme cold to modulate pain pathways, has emerged as a promising tool in chronic pain management. However, its efficacy and role within current clinical practice remain under evaluation. Methods: A narrative review was conducted by searching PubMed, Scopus, Embase, and Web of Science databases for studies published between 2010 and 2024 using the keywords “Cryoneurolysis”, “Cryoanalgesia”, “Cryoablation”, and “Chronic pain.” Only English-language studies were included. Studies that examined intraoperative cryoablation or lacked statistical analyses (except case reports) were excluded. Results: A total of 55 studies were included: 4 randomized controlled trials (RCTs), 16 retrospective studies, 4 prospective observational studies, and 31 case reports or small case series. The studies displayed significant heterogeneity in patient selection, targeted nerves, procedural protocols, and follow-up durations. While two RCTs demonstrated a significant pain reduction compared to control groups, other RCTs reported no significant improvement. Observational studies and case reports frequently report positive outcomes, with some achieving complete pain relief. Cryoneurolysis appears to be most effective in treating neuropathic pain, particularly in patients with peripheral nerve involvement. Conclusions: Cryoneurolysis is a safe technique for chronic pain management, which has been successfully applied, particularly for selected neuropathic pain conditions. However, the current evidence is limited by study heterogeneity and a lack of high-quality comparative trials. Further well-designed randomized studies are necessary to define its long-term efficacy and its potential role relative to other interventional pain therapies, such as radiofrequency ablation. Full article

Chemotherapy-induced peripheral neuropathy (CIPN) is a painful condition recalcitrant to current available therapies. CIPN pain can be severe and dose-limiting or dose-reducing for life-extending chemotherapeutics and, to date, there is no treatment to alter the progression of CIPN. For these experiments we used docetaxel, a first-line therapy for metastatic prostate cancer in humans and investigated the soluble epoxide hydrolase inhibitor EC5026 for its analgesic efficacy against this CIPN pain. Male SD rats (n = 10/group) were pretreated with 1 mg/kg EC5026 in formulated drinking water or vehicle for one week prior to docetaxel injections. The rats continued the formulated drinking water during three once-a-week docetaxel 10 mg/kg i.p. injections and were maintained on treatment until the end of week 5 when all groups were transitioned to normal drinking water. Nociceptive testing occurred throughout the entire experiment including after transitioning to normal drinking water. EC5026 increased mechanical withdrawal thresholds and latencies on the cold plate compared to docetaxel-treated controls. There were no motor effects of the compound, and the formulated drinking water provided favorable exposure. These results demonstrated that EC5026 administered prophylactically was both analgesic and able to limit the severity of mechanical and cold sensitivities in the docetaxel CIPN rat model. Full article

Background and Objectives: The common cold (acute rhinopharyngitis) and acute rhinosinusitis are highly prevalent conditions that significantly impact quality of life, often leading to nasal congestion, inflammation, and discomfort. Given the growing demand for non-pharmacological treatment options, particularly for vulnerable populations such as children and pregnant women, alternative therapies are increasingly being explored. NESOSPRAY HE-C, a nasal spray formulated with a glycerol-based filmogenic solution, acts by forming a protective osmotic film on the nasal mucosa. This mechanism facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Its purely topical and mechanical mode of action provides a non-systemic alternative for symptom management. Materials and Methods: This randomized, double-blind, parallel-group clinical trial evaluated the efficacy and safety of NESOSPRAY HE-C (n = 29) compared to a placebo nasal spray (n = 26) in patients aged ≥ 3 years diagnosed with the common cold or acute rhinosinusitis. Participants had a baseline Rhinosinusitis Symptom Severity Score (RSSS) of ≥25/50. Treatment consisted of administering 2–3 sprays per nostril, four times daily, every 4 to 6 h, for up to 8 days or until symptom resolution. The primary outcomes included changes in total RSSS, Wisconsin Upper Respiratory Symptom Survey (WURSS) score, and individual symptom scores (rhinorrhea, nasal congestion, cough, poor sleep, facial pain, and fever). Safety assessments included adverse event monitoring and treatment tolerability, with subgroup analyses performed for children and pregnant women. Results: Baseline demographics were comparable between the treatment groups. NESOSPRAY HE-C demonstrated a significantly greater reduction in total RSSS from Day 3 onward (p = 0.0008), with sustained superiority through Day 8 (p < 0.0001). Significant improvements in rhinorrhea and nasal congestion were observed within 2 h of administration (p = 0.0089), while reductions in cough (p = 0.0052), poor sleep (p = 0.0005), and facial pain (p = 0.0111) emerged by Day 3. Fever reduction was most pronounced on Days 6 (p = 0.0001) and 8 (p = 0.0312), indicating a delayed but significant effect. In terms of the WURSS score, NESOSPRAY HE-C showed a significant improvement from Day 1, with a greater reduction in symptom severity compared to placebo. This trend of greater improvement continued through Day 8. The treatment was well tolerated, with no reports of serious adverse events or allergic reactions. Efficacy was consistent across all subgroups, including children, pregnant women, and adults. Conclusions: NESOSPRAY HE-C provides rapid and sustained symptom relief for the common cold and acute rhinosinusitis, serving as a safe and effective non-pharmacological alternative to conventional treatments. By leveraging its osmotic action and barrier-forming properties, it facilitates mechanical cleansing, enhances decongestion, and reduces inflammation while preserving mucosal integrity. Additionally, by forming a protective film on the nasal mucosa, it protects against future irritations, further supporting its role as a valuable therapeutic option, particularly for individuals seeking non-systemic symptom management. Full article

Objectives: The purpose of this study is to quantitatively evaluate the combined effects of sports massage, blood flow restriction (BFR), and cold therapy on quadriceps recovery in mixed martial arts (MMA) athletes following eccentric exercise, focusing on muscle biomechanical properties, pain, and strength. Methods: This randomized, single-blind clinical trial involved 36 men and women MMA-trained participants, divided into three groups: massage (n = 12) received massage, BFR/cool (n = 12) received combined BFR and cooling, and control (n = 12) received passive rest as a control. The fatigue protocol involved MMA fighters performing five sets of plyometric jumps on a 50 cm box until exhaustion, with 1-min breaks between sets. After that, the massage group received a 20-min massage overall using standardized techniques; BFR/cool underwent a 20-min alternating blood flow restriction (200 mmHg) and cooling treatment with ice bags on the quadriceps; and the final group served as the control group with passive rest and no intervention. Participants were assessed four times—before exercise, immediately after exercise, 24 h post-exercise (after two recovery sessions), and 48 h post-exercise (after four recovery sessions)—for perfusion unit (PU), muscle elasticity, pressure pain threshold (PPT), reactive strength index (RSI), and total quality recovery (TQR). Results: The statistical analysis revealed significant effects of both massage and BFR/cooling interventions across key recovery outcomes, with large effect sizes for time-related changes in RSI (p < 0.0001; η² = 0.87), elasticity (p < 0.0001; η² = 0.84), and PPT (p < 0.0001; η² = 0.66). Notably, post-exercise 48 h values for RSI, elasticity, PU, and TQR were significantly improved in both the massage and BFR/cool groups compared to control (p < 0.05)), while no significant group differences were observed for PPT. Conclusions: The study concludes that both massage and combined blood flow restriction with cooling interventions significantly enhance post-exercise recovery—improving muscle perfusion, elasticity, reactive strength, and perceived recovery—compared to passive rest. Full article

Fibromyalgia, one of the most challenging pains to treat, lacks impartial considerations for diagnosis and useful assessment. The core symptoms are persistent extensive pain accompanied by fatigue, psychological disorders, sleep disturbance, and obesity. This study aims to explore the role of cannabinoid receptor 1 (CB1) on transient receptor potential V1 (TRPV1) signaling pathways in a mouse model of fibromyalgia. This model was subjected to intermittent cold stress (ICS) to induce fibromyalgia, as measured by the nociceptive behavior determined by von Frey and Hargreaves’ tests. Our results showed a lower mechanical threshold (2.32 ± 0.12 g) and thermal latency (4.14 ± 0.26 s) in ICS-induced fibromyalgia mice. The hyperalgesia could be alleviated by 2 Hz electroacupuncture (EA) or by TRPV1 knockout. We found decreased CB1 receptors, upregulated TRPV1, and related kinases in the dorsal root ganglion, spinal cord, hypothalamus, and periaqueductal gray in fibromyalgia mice. EA reversed these effects associated with fibromyalgia, aligning with observations in Trpv1^−/− mice. Peripheral acupoint or the intracerebral ventricle injection of a CB1 agonist significantly attenuated mechanical and thermal hyperalgesia. The EA analgesic effect was reversed by a CB1 antagonist injection, suggesting the involvement of the CB1 signaling pathway. The accurate chemogenetic activation of paraventricular nucleus (PVN), which is a structure of the hypothalamus, initiated fibromyalgia pain. The chemogenetic inhibition of PVN attenuated fibromyalgia pain via the downregulation of TRPV1 pathway. Our discoveries shed light on the involvement of CB1 in the TRPV1 signaling pathway in the effects of EA in fibromyalgia, suggesting its potential as a treatment target. Full article

Background/Objectives: The aim of this study was to assess the effects of cold-water immersion (CWI) post-eccentric muscle contraction exercise on skin temperature, pain score, maximum voluntary isometric contraction (MVIC), muscle damage, and muscle mechanical properties. Methods: Twenty-seven male participants (age 20.6 ± 0.6; body mass 69.4 ± 8.1; body fat % 13.7 ± 4.3) were divided into three treatments: whole-body CWI treatment group (n = 9), lower-body CWI treatment group (n = 9), and control treatment group (n = 9). Results: MVIC did not show a significant interaction effect between group and time but demonstrated a significant main effect for time (p = 0.001). The pain scale demonstrated a significant interaction effect between group and treatment (p = 0.049), in addition to significant main effects for both time and treatment (both p = 0.001). While blood creatine kinase (CK) concentration revealed no significant interaction effect between group and time, a significant main effect was observed for time (p = 0.001). Blood lactate dehydrogenase (LDH) concentration showed both a significant interaction effect between group and time (p = 0.02) and a significant main effect for time (p = 0.001). The tensiomyography (TMG) results for Dm showed a significant interaction effect between group and treatment (p = 0.047), as well as a significant main effect for time (p = 0.001). Conclusions: Lower-body CWI is effective in reducing pain indices and blood LDH levels, a marker of muscle damage. It may serve as an effective method for preventing and minimizing pain and muscle damage, comparable to whole-body CWI. Full article

Background: Colds are widespread infectious diseases that affect daily life, increasing healthcare costs and limiting productivity. Objectives: The aim of this study was to investigate the effects of a dietary supplement containing specific probiotic strains (L. plantarum PBS067, L. acidophilus PBS066, B. lactis BL050) on cold symptom relief, immune response enhancement, and quality of life. Methods This randomized, double-blind, placebo-controlled trial included 65 healthy volunteers (age range: 18–44 years), divided into two groups: 40 received the probiotic treatment (with vitamins and bulking agents), and 25 received placebo (vitamins and bulking agents only) for 12 weeks. Cold symptoms and systemic inflammation were assessed at three time points (baseline T0, post-treatment T1, and 6 weeks after treatment T2). Results: Probiotics were associated with a shorter average duration of cold symptoms (4.5 vs. 6.7% for Placebo, p < 0.05). At T1, fever and muscle pain occurred in 20% of participants in the Probiotic group vs. 28% and 44% in the Placebo group, respectively (p < 0.05 for muscle pain vs. Placebo). For muscle pain, a trend was maintained also at T2 (17.5% vs. 20%). The pro-inflammatory cytokine IFN-γ levels significantly decreased in the Probiotic group vs. T0 (p < 0.0001 at T1 and p < 0.01 at T2), while they increased in the Placebo group (22.279 ± 3.538 vs. 19.432 ± 3.143 pg/mL, p = NS). Although not statistically significant, at T1 the Probiotic group had higher levels of IL-10 vs. T0 (266.98 ± 78.432 vs. 240.967 ± 70.238, pg/mL p = NS). Conclusions: The probiotic mix effectively alleviated cold symptoms and reduced pro-inflammatory cytokine levels, suggesting anti-inflammatory effects. Full article

This study investigated the mechanism underlying Paeonol’s therapeutic efficacy against neuropathic pain. GSE158892 dataset data were used to conduct a scRNA-seq analysis. In cell experiments, Schwann cells and macrophages were utilized to examine pain pathogenesis using specific inhibitors. Thirty-two SD rats were randomly divided into four groups: sham, chronic constriction injury (CCI), ibuprofen, and Paeonol. Behavioral tests combined with ELISA, PCR, western blot, immunohistochemistry, and immunofluorescence analyses were conducted. CellChat analysis demonstrated that, following peripheral nerve injury, Schwann cells secreted IL-34, which interacted with CSF1R on macrophages, leading to the infiltration and activation of macrophages. Paeonol reduced IL-34 production by Schwann cells induced with LPS. Conditioned medium from LPS-stimulated Schwann cells treated with Paeonol did not cause macrophage proliferation or migration, activation of the CSF1 pathway, or ROS production. In CCI rats, Paeonol alleviated mechanical and cold hyperalgesia, while reducing the production of serum inflammatory mediators. Additionally, Paeonol decreased the expression levels of IL-34, CSF1R, phosphorylated ERK (p-ERK), phosphorylated NF-κB (p-NF-κB), and components of the NLRP3 inflammasome in the dorsal root ganglia of CCI rats. Conclusion: Alleviation of neuropathic pain by Paeonol treatment may be achieved by inhibiting the IL-34–CSF1R interaction, suppressing Schwann cell–macrophage interactions, and reducing DRG neuroinflammation. Full article

Introduction: Patients in intensive care units (ICUs) face factors that cause anxiety, fear, pain, depression, and adverse health behaviors. This qualitative study aims to determine patients’ experiences when transferred from the ICU to the ward. Methods: Thirteen individuals who were transferred from the ICU to the ward were included in this study. Interviews were conducted using a face-to-face method in the patient’s room. The interviews were recorded with a voice recorder with the consent of the patients. Codes, categories, and themes were created, and content analysis and descriptive analysis were carried out after the audio recordings were converted into text. Results: Patients reported receiving adequate physical and personal care in the ICU and were satisfied with its continuity. They felt safe due to the close attention of healthcare professionals and continuous treatment. Although they received psychological and social support from nurses, they were negatively affected by constant lights, patient noises, and nursing conversations. Patients experienced anxiety about not knowing the health status and time of day, about their relatives, their homes, and other critically ill patients in intensive care. Some patients reported fear of not being able to leave the intensive care unit, relapse, disability, or death. Patients reported pain due to the cold environment, lighting, probes, drains, and positioning. Patients suggested that healthcare personnel communicate better with them, have a clock they can see, reduce noise, and have caregivers of the same gender. They emphasized the need for moral support. Conclusions: Constant light in the intensive care unit, sounds from other patients, nurses talking among themselves, not being able to see their relatives, not knowing what time of day it is, and wondering caused anxiety in the patients. It was determined that patients experienced pain due to catheter, drain, aspiration procedures, cold environment, and position in bed. Notably, patients reported that they needed moral support and wanted to receive care from caregivers of the same gender. Full article

The adaptation of the body when exposed to a lower-than-usual temperature is a challenge that involves neuro-endocrine–immune mechanisms and affects the pharmacokinetics and/or pharmacodynamics of drugs taken before or after cold exposure. The experiments presented in this study clearly show differences in the analgesic effect of an exogenously introduced model substance (C-terminal fragment of calcium-binding protein, spermatid-specific 1) before and after cold exposure compared to its effect at an ambient temperature. The model substance used for the experiments is an octapeptide, TDIFELLK, which was synthesized via standard solid-phase peptide synthesis. Preliminary studies proved TDIFELLK’s analgesic activity. The ANOVA analysis performed showed statistically significant differences in the pain thresholds, measured by a paw pressure test, in 109 rats distributed among 14 groups and subjected to cold exposure according to different set-ups. Cold exposure immediately after TDIFELLK administration appears to enhance its analgesic effect, while cold exposure before administration reduces the effect. In some of the set-ups, antagonists of the most significant for analgesia receptors, i.e., opioid, cannabinoid, and serotonergic, were also introduced. The results showed that cold exposure had a modulating influence on the effect of the exogenously administered substances. The modulating effect was manifested differently depending on whether the intake occurred before or after cold exposure. The results also showed that the interaction with individual mediator systems was also subjected to differences depending on intake occurring before and after cold exposure. Full article

This study investigates the role of p38 mitogen-activated protein kinase (MAPK) activation in dorsal root ganglion (DRG) neurons in the development and progression of chemotherapy-induced peripheral neuropathy (CIPN). This research evaluates whether inhibiting activation of p38 MAPK could reduce neuropathic outcomes in a transgenic breast cancer mouse model (C3TAg) and wild-type mice (FVB/N) treated with cisplatin. Cisplatin treatment stimulated p38 MAPK phosphorylation and nuclear translocation in DRG neurons. Neflamapimod, a specific inhibitor of p38 MAPK alpha (p38α), proven to be safe in clinical trials, inhibited neuronal cisplatin-induced p38 MAPK phosphorylation in vitro and in vivo. Neflamapimod also reduced cisplatin-induced oxidative stress, mitochondrial dysfunction, and cleaved caspase-3 expression in DRG neurons in vitro, protecting neuronal integrity and preventing axonal damage. Functionally, neflamapimod improved mechanical and musculoskeletal hyperalgesia, and cold sensitivity in cisplatin-treated mice, reversing neuropathic pain and neurotoxicity. This study identifies p38 MAPK activation as a critical driver of CIPN and highlights its potential as a therapeutic target for CIPN. Targeting p38 MAPK activation with neflamapimod offers a promising strategy to mitigate neurotoxicity and hyperalgesia without exacerbating cancer progression, positioning it as a novel intervention for CIPN. Full article