Amyotrophic Lateral Sclerosis and Pain: A Narrative Review from Pain Assessment to Therapy.

Amyotrophic lateral sclerosis (ALS) is the most frequent neurodegenerative disease of the motor system that affects upper and lower motor neurons, leading to progressive muscle weakness, spasticity, atrophy, and respiratory failure, with a life expectancy of 2-5 years after symptom onset. In addition to motor symptoms, patients with ALS have a multitude of nonmotor symptoms; in fact, it is currently considered a multisystem disease. The purpose of our narrative review is to evaluate the different types of pain, the correlation between pain and the disease's stages, the pain assessment tools in ALS patients, and the available therapies focusing above all on the benefits of cannabis use. Pain is an underestimated and undertreated symptom that, in the last few years, has received more attention from research because it has a strong impact on the quality of life of these patients. The prevalence of pain is between 15% and 85% of ALS patients, and the studies on the type and intensity of pain are controversial. The absence of pain assessment tools validated in the ALS population and the dissimilar study designs influence the knowledge of ALS pain and consequently the pharmacological therapy. Several studies suggest that ALS is associated with changes in the endocannabinoid system, and the use of cannabis could slow the disease progression due to its neuroprotective action and act on pain, spasticity, cramps, sialorrhea, and depression. Our research has shown high patients' satisfaction with the use of cannabis for the treatment of spasticity and related pain. However, especially due to the ethical problems and the lack of interest of pharmaceutical companies, further studies are needed to ensure the most appropriate care for ALS patients.

Electroacupuncture suppresses neuronal ferroptosis to relieve chronic neuropathic pain.

Growing evidence supports the analgesic efficacy of electroacupuncture (EA) in managing chronic neuropathic pain (NP) in both patients and NP models induced by peripheral nerve injury. However, the underlying mechanisms remain incompletely understood. Ferroptosis, a novel form of programmed cell death, has been found to be activated during NP development, while EA has shown potential in promoting neurological recovery following acute cerebral injury by targeting ferroptosis. In this study, to investigate the detailed mechanism underlying EA intervention on NP, male Sprague-Dawley rats with chronic constriction injury (CCI)-induced NP model received EA treatment at acupoints ST36 and GV20 for 14 days. Results demonstrated that EA effectively attenuated CCI-induced pain hypersensitivity and mitigated neuron damage and loss in the spinal cord of NP rats. Moreover, EA reversed the oxidative stress-mediated spinal ferroptosis phenotype by upregulating reduced expression of xCT, glutathione peroxidase 4 (GPX4), ferritin heavy chain (FTH1) and superoxide dismutase (SOD) levels, and downregulating increased expression of acyl-CoA synthetase long-chain family member 4 (ACSL4), malondialdehyde levels and iron overload. Furthermore, EA increased the immunofluorescence co-staining of GPX4 in neurons cells of the spinal cord of CCI rats. Mechanistic analysis unveiled that the inhibition of antioxidant pathway of Nrf2 signalling via its specific inhibitor, ML385, significantly countered EA's protective effect against neuronal ferroptosis in NP rats while marginally diminishing its analgesic effect. These findings suggest that EA treatment at acupoints ST36 and GV20 may protect against NP by inhibiting neuronal ferroptosis in the spinal cord, partially through the activation of Nrf2 signalling.

Nursing care for parents who have experienced fetal demise: integrative review.

OBJECTIVES: to identify scientific evidence regarding nursing care for parents who have experienced grief following fetal demise. METHODS: an integrative review of original studies was conducted across six databases. The studies were classified according to the level of evidence. RESULTS: the qualitative analysis of the nine studies comprising the sample involved thematic categories, exploring the impact of perinatal loss on families, inadequate communication by healthcare professionals, and the importance of a holistic approach in care. The role of the nurse is highlighted in making a positive contribution to the team, emphasizing participation in training and the provision of essential information. FINAL CONSIDERATIONS: grieving affects not only family dynamics but also the social environment, emphasizing the urgency of a more empathetic and comprehensive approach. Care should be holistic, going beyond technical nursing assistance, and addressing the biopsychosocial context of the parents.

The trends and hotspots of research on non-pharmacological interventions for labor pain management: a bibliometric analysis.

INTRODUCTION: This study aimed to examine important points of focus, trends, and depth of research on non-pharmacological interventions for the management of labor pain worldwide from a macro perspective and present an extensive definition of research fields regarding non-pharmacological interventions. METHODS: Bibliometric methods were used in this study. With comprehensive keyword lists, the Web of Science and PubMed databases were searched using different screening strategies for publications made until 25 February 2023. RESULTS: Studies on non-pharmacological interventions in the management of labor pain have continued to develop since 2003 with great momentum. In this study, the most productive country in research on non-pharmacological interventions was found to be Iran, while Australia, the USA, China, and the United Kingdom were the most notable ones in terms of collaboration. The most prevalently studied non-pharmacological interventions were hydrotherapy and acupuncture. The results of the co-word analysis revealed 5 main themes about this field of research. CONCLUSION: The results of this study showed that interest in studies on non-pharmacological interventions in the management of labor pain has increased, the quality of research in the field is high, international collaboration is increasingly higher, and technological approaches have started to emerge in relevant studies.

COMPARISON THE EFFICACY OF DRY NEEDLING AND ISCHEMIC COMPRESSION METHODS IN MIYOFASCIAL PAIN SYNDROME: A RANDOMIZED TRIAL.

Myofascial pain syndrome (MPS) is the most common in the musculoskeletal disease. Dry needling techniques and ischemic compression are the most common applications. We aimed to compare the efficacy of dry needling and ischemic compression methods on pain, cervical range of motion and disability in myofascial pain syndrome. This is a randomized, controlled study. 98 patients with MPS were randomly assigned into three groups. Group1 received dry needling (n=33), group 2 (n=33) received ischemic compression and group 3 (n=32) received combined with dry needling and ischemic compression inventions. Additionally, all patients were given neck exercise programs including isotonic, isometric, and stretching. The severity of the pain was measured by visual analog scale (VAS). The pressure pain threshold (PPT) and cervical range of motion (ROM) were also recorded. Disability was assessed by the Neck Pain Disability Scale. All assessments were performed before the treatment and one month and three months after the treatment. There were statistically significant improvements in VAS, PPT, cervical ROM, and disability scores after one and three months in all groups compared to pre-treatment results (p<0.05). After three months of follow-up, statistically significant differences were observed in all parameters between the groups (p<0.05) except cervical ROM (p>0.05). Myofascial pain syndrome in patients with ischemic compression and dry needling effective treatment methods are shown separately in our study to be more effective when used together.

EFFECTIVENESS OF ICE APPLICATION AT SELECTED ACUPOINT (LI-4) PRIOR TO INTRAMUSCULAR INJECTION ON LEVEL OF PAIN AMONG CHILDREN IN A SELECTED HOSPITAL, CHENNAI, TAMIL NADU, INDIA.

Immunization is an effective and safest way to prevent vaccine-preventable diseases and thereby reduce morbidity and mortality in children. Injections given for immunization are the most usual ground in order to abstract agony or pain, which is the fifth vital sign leading to long-term physically and psychologically detrimental effects. A basic experimental (control group only for post-test) design using the technique of probability of simple random sampling in order to obtain sample size 105 was conducted in an Immunization Clinic at a selected PHC, Tamil Nadu, India. Ice cube was applied for about 30 seconds that is enfolded with gauze and then injected intramuscularly to administer the IM vaccine. In order to assess the pain level, an observation checklist based on Children's Hospital Eastern Ontario pain scale and Wong Baker's Faces pain scale was used. The study results manifest the higher statistical difference in the level of children's pain between the control groups and the experimental groups at a significance level of p<0.001. In order to reduce the pain level, the application of ice at LI-4 acupoint is effective. The children who are being vaccinated pass through stressful events through the application of an intramuscular injection. The findings revealed that ice application at LI-4 acupoint was very effective in pain reduction, which is a simple, safe, non-invasive, very efficient, easy-to-administer intervention and cost-effective without side effects than any other pharmacological pain intervention.

Schisandrin B from Schisandra chinensis alleviated pain via glycine receptors, Nav1.7 channels and Cav2.2 channels.

ETHNOPHARMACOLOGICAL RELEVANCE: Schisandra chinensis, the dried and ripe fruit of the magnolia family plant Schisandra chinensis (Turcz.) Baill, was commonly used in traditional analgesic prescription. Studies have shown that the extract of Schisandra chinensis (SC) displayed analgesic activity. However, the analgesic active component and the exact mechanisms have yet to be revealed. AIM OF THE STUDY: The present study was to investigate the anti-nociceptive constituent of Schisandra chinensis, assess its analgesic effect, and explore the potential molecular mechanisms. MATERIALS AND METHODS: The effects of a series of well-recognized compounds from SC on glycine receptors were investigated. The analgesic effect of the identified compound was evaluated in three pain models. Mechanistic studies were performed using patch clamp technique on various targets expressed in recombinant cells. These targets included glycine receptors, Nav1.7 sodium channels, Cav2.2 calcium channels et al. Meanwhile, primary cultured spinal dorsal horn (SDH) neurons and dorsal root ganglion (DRG) neurons were also utilized. RESULTS: Schisandrin B (SchB) was a positive allosteric modulator of glycine receptors in spinal dorsal horn neurons. The EC50 of SchB on glycine receptors in spinal dorsal horn neurons was 2.94 ± 0.28 µM. In three pain models, the analgesic effect of SchB was comparable to that of indomethacin at the same dose. Besides, SchB rescued PGE2-induced suppression of α3 GlyR activity and alleviated persistent pain. Notably, SchB could also potently decrease the frequency of action potentials and inhibit sodium and calcium channels in DRG neurons. Consistent with the data from DRG neurons, SchB was also found to significantly block Nav1.7 sodium channels and Cav2.2 channels in recombinant cells. CONCLUSION: Our results demonstrated that, Schisandrin B, the primary lignan component of Schisandra chinensis, may exert its analgesic effect by acting on multiple ion channels, including glycine receptors, Nav1.7 channels, and Cav2.2 channels.

Efficacy and safety of extracorporeal shock wave therapy combined with sodium hyaluronate in treatment of knee osteoarthritis: a systematic review and Meta-analysis.

OBJECTIVE: To assess the efficacy and safety of extracorporeal shockwave therapy (ESWT) combined with sodium hyaluronate (HA) for the treatment of knee osteoarthritis (KOA). METHODS: PubMed, Embase, the Cochrane Library, Web of Science, China National Knowledge Infrastructure, Wanfang database, China Science and Technology Journal Database, and SinoMed were searched from inception to July 2020. The quality of the randomized controlled trials was evaluated independently by two reviewers according to the criteria in the Cochrane Collaboration for Systematic Reviews. The identified articles were then screened individually using EndnoteX9 for eligibility in this Meta-analysis. The heterogeneity among the articles was evaluated using I2. RESULTS: A total of 17 studies, comprising 2000 individuals, were included in this Meta-analysis. The results showed that a significant improvement was observed in knee pain and function based on the clinical efficacy of ESWT combined with HA. Statistical analysis of clinical efficacy showed that [relative risk (RR) = 1.21, 95% confidence interval (CI) (1.12, 1.30), P < 0.01]. Statistical analysis of visual analog scale showed that [standardized mean difference (SMD) = －2.84, 95%CI (－4.01, －1.66), P < 0.01]. Western Ontario and McMaster University osteoarthritis index statistical analysis showed that [SMD = －1.57, 95% CI (－2.52, －0.61), P < 0.01]. Lysholm score statistical analysis showed that [SMD = 1.71, 95% CI (0.98, 2.44), P < 0.01]. In addition, only minor side effects, such as redness and swelling of the skin, were observed. CONCLUSIONS: Medium to low quality evidence showed that ESWT combined with HA offers an inexpensive, well-tolerated, safe, and effective method to improve pain and functionality in patients with KOA. However, tightly controlled, randomized, large multicenter trials are warranted to validate the current findings.

Effectivenss of electroacupuncture for skeletal muscle pain in Parkinson's disease: a Clinical randomized controlled trial.

OBJECTIVE: To explore the effect of electroacupuncture on skeletal muscle pain in Parkinson's disease (PD). METHODS: A single-center randomized controlled trial was conducted with sixty patients with Parkinson's disease with skeletal muscle pain were randomly divided into electroacupuncture group and sham acupuncture control group with 30 patients each. The electric acupuncture group was treated with electric acupuncture, while the control group was treated with Park needle pseudoacupuncture. Both groups were treated 5 times a week for a total of 4 weeks, and both groups completed 20 treatments. King's Parkinson's Pain Scale (KPPS) and visual analog scale (VAS) were used before and after treatment to evaluate the pain degree of patients. Real-time shear wave elastography (SWE) and modified Ashworth score (MAS) were used to evaluate the changes of muscle tone. Parkinson's comprehensive Score Scale (MDS-UPDRS, including UPDRSⅡ and UPDRS Ⅲ) was used to evaluate exercise ability. Hamilton Depression Scale (HAMD) score was used to evaluate the emotional changes of patients. Spearman correlation analysis was used to explore the correlation between pain degree and muscle tone, exercise ability and emotion. RESULTS: During the study, one case fell off in the control group, and 30 cases were eventually included in the analysis and treatment group and 29 cases in the control group. After treatment, Young's modulus of biceps and quadriceps and shear wave velocity of biceps were decreased in electroacupuncture group compared with before treatment, while KPPS score, VAS score, UPDRSⅡ, UPDRS Ⅲ and modified Ashworth score were decreased, with statistical significance (P < 0.05). There was no statistical significance in control group (P > 0.05). After treatment, KPPS score, VAS score, UPDRSⅡ and UPDRS Ⅲ, MAS, HAMD score, Young's modulus of biceps and shear wave velocity in electroacupuncture group were significantly lower than those in control group (P < 0.05). Spearman correlation analysis showed that KPPS score was positively correlated with UPDRS Ⅲ (r = 0.414, P < 0.05). KPPS score was positively correlated with HAMD score (r = 0.576, P < 0.01). CONCLUSION: Electroacupuncture therapy can effectively improve skeletal muscle pain in patients with Parkinson's disease, reduce the muscle hardness of patients, improve patients' daily life ability, and improve patients' emotional disorders. The degree of skeletal muscle pain in PD patients is correlated with motor ability and emotional disorders, but there is no significant correlation between the degree of skeletal muscle pain and the muscle tone of PD patients.

Unlocking hypnotizability: Transcranial brain stimulation for enhanced impact in chronic pain.

Hypnosis provides a therapeutic option for health issues like chronic pain, but individual responsiveness, termed hypnotizability, varies. Faerman et al.'s1 study showed that transcranial magnetic stimulation (TMS) can significantly improve hypnotizability, offering potential for patients with limited response to hypnosis in pain management.

Electroacupuncture promotes macrophage/microglial M2 polarization and suppresses inflammatory pain through AMPK.

Inflammatory pain, the most prevalent disease globally, remains challenging to manage. Electroacupuncture emerges as an effective therapy, yet its underlying mechanisms are not fully understood. This study investigates whether adenosine 5'-monophosphate (AMP)-activated protein kinase (AMPK)-regulated silent information regulator 1 (SIRT1) contributes to electroacupuncture's antinociceptive effects by modulating macrophage/microglial polarization in the spinal dorsal horn of a mouse model of inflammatory pain. In this study, mice, introduced to inflammatory pain through subcutaneous injections of complete freund's adjuvant (CFA) in the plantar area, underwent electroacupuncture therapy every alternate day for 30-min sessions. The assessment of mechanical allodynia and thermal hyperalgesia in these subjects was carried out using paw withdrawal frequency and paw withdrawal latency measurements, respectively. Western blot analysis measured levels of AMPK, phosphorylation-adenosine 5'-monophosphate (AMP)-activated protein kinase, SIRT1, inducible nitric oxide synthase, cluster of differentiation 86, arginase 1, and interleukin 10. In contrast to the group treated solely with CFA, the cohort receiving both CFA and electroacupuncture demonstrated notable decreases in both thermal hyperalgesia and mechanical allodynia. This was accompanied by a marked enhancement in AMPK phosphorylation levels. AMPK knockdown reversed electroacupuncture's analgesic effects and reduced M2 macrophage/microglial polarization enhancement. Additionally, AMPK knockdown significantly weakened electroacupuncture-induced SIRT1 upregulation, and EX-527 injection attenuated electroacupuncture's facilitation of M2 macrophage/microglial polarization without affecting AMPK phosphorylation levels. Furthermore, combining electroacupuncture with SRT1720 enhanced the analgesic effect of SRT1720. Our findings suggest that AMPK regulation of SIRT1 plays a critical role in electroacupuncture's antinociceptive effect through the promotion of M2 macrophage/microglial polarization.

Observation of the efficacy of elongated needle therapy in treating patients with â ¢B prostatitis of stagnant dampness-heat syndrome. / 芒针治疗湿热瘀阻证⠢Båž‹å‰åˆ—è ºç‚Žæ‚£è€ çš„ç–—æ•ˆè§‚å¯Ÿ.

OBJECTIVES: To observe the clinical efficacy in patients with ⅢB prostatitis of stagnant dampness-heat syndrome treated with elongated needle therapy. METHODS: A total of 90 patients with ⅢB prostatitis of stagnant dampness-heat syndrome were selected and randomly divided into a treatment group(45 cases, 2 dropped out) and a control group(45 cases, 1 dropped out) using a random number table method. The control group was treated with oral administration of Qianlie Shutong Capsule, 3 capsules per dose, 3 times a day for a total of 4 weeks. The treatment group received elongated needle therapy at Qihai(CV6), Zhongji(CV3), bilateral Zhibian(BL54) and Shuidao(ST28), with one treatment per day for 4 weeks. Before and after treatment, the traditional Chinese medicine syndrome score, National Institutes of Health Chronic Prostatitis Symptom Index(NIH-CPSI) score were compared between the two groups, and the clinical efficacy was compared after treatment. RESULTS: Compared with that before treatment, the control group showed significant decrease in traditional Chinese medicine syndrome score, testicular pain, urinary frequency, unending remnants of urine, scrotal wetness, yellowish urine, urinary symptoms, and quality of life scores after treatment(P<0.05)；the treatment group showed significant decrease in traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain, scrotal wetness, yellowish urine scores, NIH-CPSI total score, pain symptoms, urinary symptoms, and quality of life scores after treatment(P<0.05). After treatment, the treatment group showed significantly lower traditional Chinese medicine syndrome score, and perineal pain, groin pain, pelvic pain, testicular pain scores, NIH-CPSI total score, pain symptoms, and quality of life scores than those of the control group(P<0.05). The effective rate in the treatment group (63.64%, 28/43) was significantly higher than that in the control group (88.37%, 38/44, P<0.05). CONCLUSIONS: Elongated needle therapy can significantly improve the traditional Chinese medicine syndrome score, NIH-CPSI total score, and pain symptom scores in patients with ⅢB prostatitis of stagnant dampness-heat syndrome. It can significantly improve the cure rate in these patients and is particularly effective in relieving pain.

Changes in pharmacist's recommendations of over-the-counter treatments for the common cold during the COVID-19 pandemic.

BACKGROUND: The common cold is one of the most frequently occurring illnesses worldwide. The aim of this study was to determine which OTC anti-common cold medications were most often recommended by pharmacists and if the COVID-19 pandemic affected such recommendations. METHODS: Non-interventional, observational research trial using a self-developed questionnaire to collect data on pharmacists' recommendations for anti-common cold OTC treatment. The data were collected during the COVID-19 pandemic (December 2021-February 2022) in four large community network pharmacies in Lodz (Poland) and then compared with an analogue period of time before the pandemic (December 2019-February 2020). RESULTS: During COVID-19 pandemic there was a significant (p < 0.05) reduction in paracetamol, acetylsalicylic acid, metamizole magnesium, inosines, alpha-mimetics, mucolytics, homeopathics, and sore throat products and an increase in other tablets/capsules and add-on product recommendations. There was a significant relationship (p < 0.05, OR > 1) between the recommended frequency of paracetamol, inosines, sore throat products (each symptom), metamizole magnesium (headache, fever), acetylsalicylic acid (headache, fever, fatigue), NSAIDs, alpha-mimetics (headache, rhinorrhea), pseudoephedrine (rhinorrhea), homeopathics (headache), herbal products (fatigue), antihistamines (rhinorrhea, cough), and mucolytics (headache, fever, cough). CONCLUSIONS: Favorable prices (before COVID-19 pandemic) and reports on common NSAIDs side effects (beginning of the pandemic) led to high sale of paracetamol. Increased awareness of clinical effectiveness of some medications or their reduced availability influenced their limited recommendations.

Symptom burden and relief in palliative care units of German Comprehensive Cancer Center and other hospitals.

PURPOSE: The National Hospice and Palliative Registry contains patient data from German hospice and palliative care facilities about symptoms. The aim of the study at hand is to differentiate symptom burden of patients in palliative care units between Comprehensive Cancer Center (CCC) and other hospitals regarding symptom burden and relief of patients in palliative care units. METHODS: The registry analysis provided data of patients in palliative care units (2014-2018). We analyzed characteristic and symptom-related data on 18 symptoms, with considerable symptom-burdened patients (moderate or severe). We followed a cancer (yes/no) and facility-specific descriptive analysis (f, %, µ, Mdn, SD, V, r) using SPSS. RESULTS: We evaluated 10,447 patient records (CCC: 4234 pts/non CCC 6,213 pts), 82% with a cancer diagnosis. For cancer patients, the mean age in CCC-affiliated palliative care units was 68 (SD 19-99) years, in others 73 (SD 23-104) years (p < 0.05; V = 0.2). The proportion of patients with significant symptom burden is lower in CCC-affiliated than in other palliative care units. The difference between facilities shows a significant weak effect in pain, vomiting and constipation, depressiveness, anxiety, and tension. The proportion of cases which symptom burden could be alleviated is higher in CCC-affiliated palliative care units with significant weak/medium effect in pain, nausea, vomiting, shortness of breath, constipation, wound care problems, depressiveness, anxiety, tension, confusion, and problems in organizing care. CONCLUSION: We found differences in symptom burden and symptom relief between CCC-affiliated and other palliative care units. CCCs should continue to feel responsible for sharing knowledge about symptom relief, such as through standard operating procedures and education.

Effect of Reflexology on Pain, Fatigue, Sleep Quality, and Lactation in Postpartum Primiparous Women After Cesarean Delivery: A Randomized Controlled Trial.

BACKGROUND: Mothers commonly experience pain, fatigue, sleep disruption, and breastfeeding problems after cesarean delivery. To date, no follow-up study has examined all of these variables to evaluate the utility of reflexology in reducing these problems and supporting breastfeeding. RESEARCH AIM: This study aimed to determine the effect of foot reflexology performed in the postpartum period on pain, fatigue, sleep quality, and lactation in primiparous women who underwent cesarean delivery. METHODS: This is a two-arm, parallel-group randomized controlled trial. Data were collected between January 1, 2020, and January 31, 2021, with a sample of 80 women who were randomly assigned to the reflexology (n = 40) and control (n = 40) groups. The reflexology group received 40 minutes of foot reflexology once a week for 8 weeks. The primary outcomes of the study were pain, fatigue, sleep quality, and breastfeeding efficacy. RESULTS: Pain scores in the reflexology group decreased by 90.9% in week 1, 90.2% in week 2, and 59.8% in week 3 compared to the control group. Pain resolved at week 4 in the reflexology group and week 7 in the control group. The reflexology group showed a 36.9% decrease in fatigue level, a 48.0% increase in energy level, a 70.7% increase in sleep quality, and a 20.2% increase in breastfeeding efficacy compared to the control group (p < 0.05). CONCLUSIONS: Foot reflexology reduces postpartum symptoms and positively affects breastfeeding and can be used safely in postnatal care practices.

Electroacupuncture attenuates nociceptive behaviors in a mouse model of cancer pain.

Pain is a major symptom in cancer patients, and cancer-induced bone pain (CIBP) is the most common type of moderate and severe cancer-related pain. The current available analgesic treatments for CIBP have adverse effects as well as limited therapeutic effects. Acupuncture is proved effective in pain management as a safe alternative therapy. We evaluated the analgesic effect of acupuncture in treatment of cancer pain and try to explore the underlying analgesic mechanisms. Nude mice were inoculated with cancer cells into the left distal femur to establish cancer pain model. Electroacupuncture (EA) treatment was applied for the xenograft animals. Pain behaviors of mice were evaluated, followed by the detections of neuropeptide-related and inflammation-related indicators in peripheral and central levels. EA treatment alleviated cancer-induced pain behaviors covering mechanical allodynia, thermal hyperalgesia and spontaneous pain, and also down-regulated immunofluorescence expressions of neuropeptide CGRP and p75 in the skin of affected plantar area in xenograft mice, and inhibited expressions of overexpressed neuropeptide-related and inflammation-related protein in the lumbar spinal cord of xenograft mice. Overall, our findings suggest that EA treatment ameliorated cancer-induced pain behaviors in the mouse xenograft model of cancer pain, possibly through inhibiting the expressions of neuropeptide-related and inflammation-related protein in central level following tumor cell xenografts.

Sodium butyrate alleviates experimental autoimmune prostatitis by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway.

BACKGROUND: Chronic prostatitis and chronic pelvic pain syndrome (CP/CPPS) leads to severe discomfort in males and loss of sperm quality. Current therapeutic options have failed to achieve satisfactory results. Sodium butyrate (NaB) plays a beneficial role in reducing inflammation, increasing antioxidant capacities, and improving organ dysfunction; additionally NaB has good safety prospects and great potential for clinical application. The purpose of the current research was to study the effect of NaB on CP/CPPS and the underlying mechanisms using a mouse model of experimental autoimmune prostatitis (EAP) mice. METHODS: The EAP mouse model was successfully established by subcutaneously injecting a mixture of prostate antigen and complete Freund's adjuvant. Then, EAP mice received daily intraperitoneal injections of NaB (100, 200, or 400 mg/kg/day) for 16 days, from Days 26 to 42. We then explored anti-inflammatory potential mechanisms of NaB by studying the effects of Nrf2 inhibitor ML385 and HO-1 inhibitor zinc protoporphyrin on prostate inflammation and pelvic pain using this model. On Day 42, hematoxylin-eosin staining and dihydroethidium staining were used to evaluate the histological changes and oxidative stress levels of prostate tissues. Chronic pelvic pain was assessed by applying Von Frey filaments to the lower abdomen. The levels of inflammation-related cytokines, such as interleukin (IL)-1ß, IL-6, and tumor necrosis factor were detected by enzyme-linked immunosorbent assay. The regulation of Nrf2/HO-1 signaling pathway and the expression of NLRP3 inflammasome-related protein in EAP mice were detected by western blot analysis assay. RESULTS: Compared with the EAP group, chronic pain development, histological manifestations, and cytokine levels showed that NaB reduced the severity of EAP. NaB treatment could inhibit NLRP3 inflammasome activation. Mechanism studies showed that NaB intervention could alleviate oxidative stress in EAP mice through Nrf2/HO-1 signal pathway. Nrf2/HO-1 pathway inhibitors can inhibit NaB -mediated oxidative stress. The inhibitory effect of NaB on the activation of NLRP3 inflammasome and anti-inflammatory effect can also be blocked by Nrf2/HO-1 pathway. CONCLUSIONS: NaB treatment can alleviates prostatic inflammation and pelvic pain associated with EAP by inhibiting oxidative stress and NLRP3 inflammasome activation via the Nrf2/HO-1 pathway. NaB has the potential as an effective agent in the treatment of EAP.

Massage ameliorates lumbar disc herniation-related radicular pain in rats by suppressing TLR4/NLRP3 inflammasome signaling transduction.

BACKGROUND: Lumbar disc herniation (LDH) is a common spinal disease that can cause severe radicular pain. Massage, also known as Tuina in Chinese, has been indicated to exert an analgesic effect in patients with LDH. Nonetheless, the mechanism underlying this effect of massage on LDH remains unclarified. METHODS: Forty Sprague-Dawley rats were randomly divided into four groups. A rat LDH model was established by autologous nucleus pulpous (NP) implantation, followed by treatment with or without massage. A toll-like receptor 4 (TLR4) antagonist TAK-242 was administrated to rats for blocking TLR4. Behavioral tests were conducted to examine rat mechanical and thermal sensitivities. Western blotting was employed for determining TLR4 and NLRP3 inflammasome-associated protein levels in the spinal dorsal horn (SDH). Immunofluorescence staining was implemented for estimating the microglial marker Iba-1 expression in rat SDH tissue. RESULTS: NP implantation induced mechanical allodynia and thermal hyperalgesia in rat ipsilateral hindpaws and activated TLR4/NLRP3 inflammasome signaling transduction in the ipsilateral SDH. Massage therapy or TAK-242 administration relieved NP implantation-triggered pain behaviors in rats. Massage or TAK-242 hindered microglia activation and blocked TLR4/NLRP3 inflammasome activation in ipsilateral SDH of LDH rats. CONCLUSION: Massage ameliorates LDH-related radicular pain in rats by suppressing microglia activation and TLR4/NLRP3 inflammasome signaling transduction.

Reinforcing informed medication prescription for low back pain in the emergency department (RIME): a controlled interrupted time series implementation study protocol.

INTRODUCTION: Management guidelines for low back pain (LBP) recommend exclusion of serious pathology, followed by simple analgesics, superficial heat therapy, early mobilisation and patient education. An audit in a large metropolitan hospital emergency department (ED) revealed high rates of non-recommended medication prescription for LBP (65% of patients prescribed opioids, 17% prescribed benzodiazepines), high inpatient admission rates (20% of ED LBP patients), delayed patient mobilisation (on average 6 hours) and inadequate patient education (48% of patients). This study aims to improve medication prescription for LBP in this ED by implementing an intervention shown previously to improve guideline-based management of LBP in other Australian EDs. METHODS AND ANALYSIS: A controlled interrupted time series study will evaluate the intervention in the ED before (24 weeks; 20 March 2023-3 September 2023) and after (24 weeks; 27 November 2024-12 May 2024) implementation (12 weeks; 4 September 2023-26 November 2023), additionally comparing findings with another ED in the same health service. The multicomponent implementation strategy uses a formalised clinical flow chart to support clinical decision-making and aims to change clinician behaviour, through clinician education, provision of alternative treatments, educational resources, audit and feedback, supported by implementation champions. The primary outcome is the percentage of LBP patients prescribed non-recommended medications (opioids, benzodiazepines and/or gabapentinoids), assessed via routinely collected ED data. Anticipated sample size is 2000 patients (n=1000 intervention, n=1000 control) based on average monthly admissions of LBP presentations in the EDs. Secondary outcomes include inpatient admission rate, time to mobilisation, provision of patient education, imaging requests, representation to the ED within 6 months and healthcare costs. In nested qualitative research, we will study ED clinicians' perceptions of the implementation and identify how benefits can be sustained over time. ETHICS AND DISSEMINATION: This study received ethical approval from the Metro North Human Research Ethics Committee (HREC/2022/MNHA/87995). Study findings will be published in peer-reviewed journals and presented at international conferences and educational workshops. TRIAL REGISTRATION NUMBER: ACTRN12622001536752.