Electroacupuncture Attenuates Fibromyalgia Pain via Toll-like Receptor 4 in the Mouse Brain.

BACKGROUND: Fibromyalgia (FM) is characterized by complex pain symptoms lacking impersonal considerations in diagnosis and treatment evaluation, which often happens in women. Chronic and persistent widespread pain is the key symptom disturbing patients with FM, leading to depression, obesity, and sleep disturbances. Toll-like receptor 4 (TLR4) activation produces a harmful sensory input involved in central pain; this is the focus of this study. Electroacupuncture (EA) has beneficial effects in reducing FM pain, but its connection with TLR4 signaling is still unknown. METHODS: Intermittent cold stress significantly induced mechanical and thermal pain. EA, but not sham EA, reliably attenuated mechanical and thermal hyperalgesia. The increased inflammatory mediators in FM mice were reduced in the EA group, but not in the sham group. RESULTS: All TLR4 and related molecule levels increased in the FM mice's hypothalamus, periaqueductal gray (PAG), and cerebellum. These increases could be attenuated by EA but not sham stimulation. Activation of TLR4 by lipopolysaccharide (LPS) significantly induced FM and can be further reversed by a TLR4 antagonist. CONCLUSIONS: These mechanisms provide evidence that the analgesic effect of EA is related to the TLR4 pathway. In addition, we showed that inflammation can activate the TLR4 pathway and provided new possible therapeutic targets for FM pain.

Acupuncture points injection mitigates chronic pain through transient receptor potential V1 in mice.

Objectives: Tissue injury in peripheral sites can result in long-term potentiation in nociceptive neurons and surrounding glial cells, potentially resulting in the development of chronic inflammatory pain (CIP). Acupoint injection (AI) is similar to Western phototherapy, which injects solutions at specific sites to mitigate chronic pain. AI has shown greater benefits compared with acupuncture. In this study, we examined the therapeutic effect and explored the underlying mechanisms of AI in mice CIP model. Materials and Methods: We injected thrice complete Freund's adjuvant (CFA) into the mouse's hind paw to induce CIP. Results: We found that, after two weeks, CFA injection significantly induced mechanical and thermal hyperalgesia which were attenuated by AI treatment. Transient receptor potential V1 (TRPV1) channels and associated molecules were all increased in CIP in mice dorsal root ganglion (DRG), spinal cord (SC), thalamus, and somatosensory cortex (SSC). The aforementioned molecules were mitigated in AI and Trpv1 knockout mice. Furthermore, Iba1-positive cells (microglial marker) were also potentiated and shared a similar tendency with TRPV1. Conclusion: These findings suggest that AI can alleviate chronic pain by reducing TRPV1 overexpression in both neuronal and microglial cells. Our results suggest new potential therapeutic targets for AI in chronic pain.

Increased risk of tinnitus in patients with temporomandibular disorder: a retrospective population-based cohort study.

This study determined whether there is an increased risk of tinnitus in patients with temporomandibular joint (TMJ). We used information from health insurance claims obtained from Taiwan National Health Insurance (TNHI). Patients aged 20 years and older who were newly diagnosed with TMJ disorder served as the study cohort. The demographic factors and comorbidities that may be associated with tinnitus were also identified, including age, sex, and comorbidities of hearing loss, noise effects on the inner ear, and degenerative and vascular ear disorders. A higher proportion of TMJ disorder patients suffered from hearing loss (5.30 vs. 2.11 %), and degenerative and vascular ear disorders (0.20 vs. 0.08 %) compared with the control patients. The crude hazard ratio (HR) of tinnitus in the TMJ disorder cohort was 2.73-fold higher than that in the control patients, with an adjusted HR of 2.62 (95 % CI = 2.29-3.00). The comorbidity-specific TMJ disorder cohort to the control patients' adjusted HR of tinnitus was higher for patients without comorbidity (adjusted HR = 2.75, 95 % CI = 2.39-3.17). We also observed a 3.22-fold significantly higher relative risk of developing tinnitus within the 3-year follow-up period (95 % CI = 2.67-3.89). Patients with TMJ disorder might be at increased risk of tinnitus.

Statin Use Reduces Prostate Cancer All-Cause Mortality: A Nationwide Population-Based Cohort Study.

Studies have suggested that statin use is related to cancer risk and prostate cancer mortality. We conducted a population-based cohort study to determine whether using statins in prostate cancer patients is associated with reduced all-cause mortality rates. Data were obtained from the Taiwan National Health Insurance Research Database. The study cohort comprised 5179 patients diagnosed with prostate cancer who used statins for at least 6 months between January 1, 1998 and December 31, 2010. To form a comparison group, each patient was randomly frequency-matched (according to age and index date) with a prostate cancer patient who did not use any type of statin-based drugs during the study period. The study endpoint was mortality. The hazard ratio (HR) and 95% confidence interval (CI) were estimated using Cox regression models. Among prostate cancer patients, statin use was associated with significantly decreased all-cause mortality (adjusted HR = 0.65; 95% CI = 0.60-0.71). This phenomenon was observed among various types of statin, age groups, and treatment methods. Analyzing the defined daily dose of statins indicated that both low- and high-dose groups exhibited significantly decreased death rates compared with nonusers, suggesting a dose-response relationship. The results of this population-based cohort study suggest that using statins reduces all-cause mortality among prostate cancer patients, and a dose-response relationship may exist.

Population-based cohort study on the increase in the risk for type 2 diabetes mellitus development from nonapnea sleep disorders.

OBJECTIVES: The evidence concerning the relationship between nonapnea sleep disorders and the risk for type 2 diabetes mellitus (DM) is scant and elusive. Our study aimed to examine if nonapnea sleep disorders increase the risk for DM using a population-based retrospective cohort study from 1997 to 2010. METHODS: In the Taiwan's National Health Insurance Research Database (NHIRD), 45,602 patients with nonapnea sleep disorders were identified as the study cohort. The comparison cohort was formed by 91,204 age- and gender-matched controls. Cox proportional hazards regression model was used to estimate the risk for developing DM. RESULTS: In 45,602 patients with nonapnea sleep disorders, 7241 new cases of DM were reported during the follow-up period. The mean follow-up time was 9.04 (standard deviation [SD], 3.33) and 8.96 (SD, 3.47) for the nonapnea sleep disorders cohort and the comparison cohort, respectively. The incidence rate of DM was higher in the nonapnea sleep disorder cohort than in the comparison cohort (17.6 vs 13.3 per 1000 individuals-years). Overall, patients with nonapnea sleep disorders had a higher risk for DM compared to patients without nonapnea sleep disorders (adjusted hazard ratio [HR], 1.05 [95% confidence interval {CI}, 1.02-1.08]). Men with nonapnea sleep disorders had a higher risk for DM than the men in the comparison group (adjusted HR, 1.08 [95% CI, 1.03-1.14]). Among subjects aged less than 40years, patients with nonapnea sleep disorders had a higher risk for DM than the comparison group (adjusted HR, 1.42 [95% CI, 1.27-1.59]). Compared with the comparison cohort, patients with sleep disturbance had an 11% higher risk for DM (adjusted HR, 1.11 [95% CI, 1.07-1.16]). CONCLUSION: Compared to patients without nonapnea sleep disorders, patients with nonapnea sleep disorders had a higher risk for developing DM, especially among those who were less than 40years of age and who had sleep disturbances.