Eicosapentaenoic Acid Modulates Transient Receptor Potential V1 Expression in Specific Brain Areas in a Mouse Fibromyalgia Pain Model.

Pain is an unpleasant sensory and emotional experience accompanied by tissue injury. Often, an individual's experience can be influenced by different physiological, psychological, and social factors. Fibromyalgia, one of the most difficult-to-treat types of pain, is characterized by general muscle pain accompanied by obesity, fatigue, sleep, and memory and psychological concerns. Fibromyalgia increases nociceptive sensations via central sensitization in the brain and spinal cord level. We used intermittent cold stress to create a mouse fibromyalgia pain model via a von Frey test (day 0: 3.69 ± 0.14 g; day 5: 2.13 ± 0.12 g). Mechanical pain could be reversed by eicosapentaenoic acid (EPA) administration (day 0: 3.72 ± 0.14 g; day 5: 3.69 ± 0.13 g). A similar trend could also be observed for thermal hyperalgesia. The levels of elements in the transient receptor potential V1 (TRPV1) signaling pathway were increased in the ascending pain pathway, including the thalamus, medial prefrontal cortex, somatosensory cortex, anterior cingulate cortex, and cerebellum. EPA intake significantly attenuated this overexpression. A novel chemogenetics method was used to inhibit SSC and ACC activities, which presented an analgesic effect through the TRPV1 downstream pathway. The present results provide insights into the role of the TRPV1 signaling pathway for fibromyalgia and its potential as a clinical target.

Electroacupuncture Reduces Fibromyalgia Pain via Neuronal/Microglial Inactivation and Toll-like Receptor 4 in the Mouse Brain: Precise Interpretation of Chemogenetics.

Fibromyalgia (FM) is a complex, chronic, widespread pain syndrome that can cause significant health and economic burden. Emerging evidence has shown that neuroinflammation is an underlying pathological mechanism in FM. Toll-like receptors (TLRs) are key mediators of the immune system. TLR4 is expressed primarily in microglia and regulates downstream signaling pathways, such as MyD88/NF-κB and TRIF/IRF3. It remains unknown whether electroacupuncture (EA) has therapeutic benefit in attenuating FM pain and what role the TLR4 pathway may play in this effect. We compared EA with sham EA to eliminate the placebo effect due to acupuncture. We demonstrated that intermittent cold stress significantly induced an increase in mechanical and thermal FM pain in mice (mechanical: 2.48 ± 0.53 g; thermal: 5.64 ± 0.32 s). EA but not sham EA has an analgesic effect on FM mice. TLR4 and inflammatory mediator-related molecules were increased in the thalamus, medial prefrontal cortex, somatosensory cortex (SSC), and amygdala of FM mice, indicating neuroinflammation and microglial activation. These molecules were reduced by EA but not sham EA. Furthermore, a new chemogenetics method was used to precisely inhibit SSC activity that displayed an anti-nociceptive effect through the TLR4 pathway. Our results imply that the analgesic effect of EA is associated with TLR4 downregulation. We provide novel evidence that EA modulates the TLR4 signaling pathway, revealing potential therapeutic targets for FM pain.

Chemogenetics Modulation of Electroacupuncture Analgesia in Mice Spared Nerve Injury-Induced Neuropathic Pain through TRPV1 Signaling Pathway.

Neuropathic pain, which is initiated by a malfunction of the somatosensory cortex system, elicits inflammation and simultaneously activates glial cells that initiate neuroinflammation. Electroacupuncture (EA) has been shown to have therapeutic effects for neuropathic pain, although with uncertain mechanisms. We suggest that EA can reliably cure neuropathic disease through anti-inflammation and transient receptor potential V1 (TRPV1) signaling pathways from the peripheral to the central nervous system. To explore this, we used EA to treat the mice spared nerve injury (SNI) model and explore the underlying molecular mechanisms through novel chemogenetics techniques. Both mechanical and thermal pain were found in SNI mice at four weeks (mechanical: 3.23 ± 0.29 g; thermal: 4.9 ± 0.14 s). Mechanical hyperalgesia was partially attenuated by 2 Hz EA (mechanical: 4.05 ± 0.19 g), and thermal hyperalgesia was fully reduced (thermal: 6.22 ± 0.26 s) but not with sham EA (mechanical: 3.13 ± 0.23 g; thermal: 4.58 ± 0.37 s), suggesting EA's specificity. In addition, animals with Trpv1 deletion showed partial mechanical hyperalgesia and no significant induction of thermal hyperalgesia in neuropathic pain mice (mechanical: 4.43 ± 0.26 g; thermal: 6.24 ± 0.09 s). Moreover, we found increased levels of inflammatory factors such as interleukin-1 beta (IL1-ß), IL-3, IL-6, IL-12, IL-17, tumor necrosis factor alpha, and interferon gamma after SNI modeling, which decreased in the EA and Trpv1-/- groups rather than the sham group. Western blot and immunofluorescence analysis showed similar tendencies in the dorsal root ganglion, spinal cord dorsal horn, somatosensory cortex (SSC), and anterior cingulate cortex (ACC). In addition, a novel chemogenetics method was used to precisely inhibit SSC to ACC activity, which showed an analgesic effect through the TRPV1 pathway. In summary, our findings indicate a novel mechanism underlying neuropathic pain as a beneficial target for neuropathic pain.

Acupoint catgut embedding attenuates fibromyalgia pain through attenuation of TRPV1 signaling pathway in mouse.

Objectives: Chronic pain is considered as pain lasting for more than three months and has emerged as a global health problem affecting individuals and society. Chronic extensive pain is the main syndrome upsetting individuals with fibromyalgia (FM), accompanied by anxiety, obesity, sleep disturbances, and depression, Transient receptor potential vanilloid 1 (TRPV1) has been reported to transduce inflammatory and pain signals to the brain. Materials and Methods: Acupoint catgut embedding (ACE) is a novel acupuncture technique that provides continuous effects and convenience. ACE was performed at the bilateral ST36 acupoint. Results: We demonstrated similar pain levels among all groups at baseline. After cold stress, chronic mechanical or thermal nociception was induced (D14: mechanical: 1.85 ± 0.13 g; thermal: 4.85 ± 0.26 s) and reversed in ACE-treated mice (D14: mechanical: 3.99 ± 0.16 g; thermal: 7.42 ± 0.45 s) as well as Trpv1-/- group (Day 14, mechanical: 4.25 ± 0.2 g; thermal: 7.91 ± 0.21 s) mice. Inflammatory mediators were augmented in FM individuals and were abridged after ACE management and TRPV1 gene loss. TRPV1 and its linked mediators were increased in the thalamus (THA), somatosensory cortex (SSC), medial prefrontal cortex (mPFC), and anterior cingulate cortex (ACC) in FM mice. The up-regulation of these mediators was diminished in ACE and Trpv1-/- groups. Conclusion: We suggest that chronic pain can be modulated by ACE or Trpv1-/-. ACE-induced analgesia via TRPV1 signaling pathways may be beneficial targets for FM treatment.

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.

Acupressure Improves Cognition and Quality of Life Among Older Adults with Cognitive Disorders in Long-Term Care Settings: A Clustered Randomized Controlled Trial.

OBJECTIVE: To examine the effectiveness of acupressure on cognition and quality of life (QoL) among older adults with cognitive disorders residing in long-term care (LTC) settings. DESIGN: A clustered, randomized, assessor-blinded, controlled trial with a repeated measures design. SETTING AND PARTICIPANTS: Participants were recruited from residential care facilities in Taiwan from August 2020 to February 2021. Ninety-two older residents in 18 facilities were randomized to either the intervention arm (9 facilities, n = 46) or the control arm (9 facilities, n = 46). METHODS: Acupressure was performed at Baihui (GV20), Sishencong (EX-HN1), Shenting (GV24), Fengchi (GB20), Shuigou (GV26), Neiguan (PC6), Shenmen (HT7), and Zusanli (ST36). The duration for pressing each acupoint was 3 minutes. The acupressure force was maintained at 3 kg. Acupressure was performed once a day 5 times a week for 12 weeks. The primary outcome measure was the Cognitive Abilities Screening Instrument (CASI). Secondary outcomes included the digit span backward test, the Wisconsin Card Sorting Test (perseverative responses, perseverative errors, and categories completed), semantic fluency tests of categories of animals, fruits, and vegetables, and the Quality of Life-Alzheimer's Disease (QoL-AD). Data were collected at preintervention and postintervention. Three-level mixed effects models were performed. This study complied with the CONSORT checklist. RESULTS: After adjusting for covariates, there was a significant increase in CASI scores, the digit span backward test, perseverative responses, perseverative errors, categories completed, semantic fluency tests of categories, and QoL-AD scores in the intervention versus control arm at 3 months. CONCLUSIONS AND IMPLICATIONS: This study provides support for the use of acupressure to improve cognition and QoL during care among older residents with cognitive disorders in LTC settings. Acupressure can be integrated into aged care practice to improve cognition and QoL of older residents with cognitive disorders in LTC settings.

Clinical efficacy and immune effects of acupuncture in patients with comorbid chronic pain and major depression disorder: A double-blinded, randomized controlled crossover study.

BACKGROUND: Depression and pain are highly comorbid and share biological mechanisms. Acupuncture is commonly used to manage both pain and depression, but the choice of acupoints for specific disorders differs. This study aimed to investigate whether specific acupuncture intervention on pain- and depression-acupoints would have specific efficacy and immune effects in patients with comorbid chronic pain and major depressive disorder (MDD). METHODS: We performed a subject- and assessor-blinded, crossover, and randomized controlled clinical trial of depression- and pain-specific acupuncture intervention and measured clinical responses and proinflammatory cytokines in patients with comorbid chronic pain and MDD. Specific acupoints for pain and depression were used in random order with a washout interval. Forty-seven patients were enrolled and randomly assigned to two groups: (1) the depression-pain group (23 patients who were treated with depression-specific acupoints and then the pain-specific acupoints after the washout) and (2) pain-depression group (24 patients with the reverse order). RESULTS: The pain-specific acupoints for pain did not reduce Brief Pain Inventory scores to a significantly greater degree (-0.97 ± 1.69) than the depression-specific acupoints (-0.28 ± 1.88); likewise, the depression-specific acupoints did not significantly ameliorate Hamilton Depression Rating Scale (-4.59 ± 6.02) than the pain-specific acupoints (-6.69 ± 6.61). The pain-specific acupoints improved Beck Depression Inventory-Second Edition (-6.74 ± 9.76) even better than the depression-specific acupoints (-1.92 ± 10.74). The depression-specific acupoints did not significantly decrease the depression-related interleukin (IL)-6 level (-1.24 ± 6.67) than the pain-specific acupoints (-0.60 ± 4.36). The changed levels of IL-1ß, tumor necrosis factor (TNF)-α between the depression-specific acupoints (-37.41 ± 194.49; -12.53 ± 54.68) and the pain-specific acupoints (-15.46 ± 87.56; -7.28 ± 27.86) could not reach significantly different, too. CONCLUSION: This study rejected our hypothesis that the pain-specific acupoints might produce superior analgesic effects than the depression-specific acupoints and vice versa. The cytokine results might imply that pain and depression share common biological mechanisms. (trial registration: https://www. CLINICALTRIALS: gov: NCT03328819).

Paper-Based Detection Device for Microenvironment Examination: Measuring Neurotransmitters and Cytokines in the Mice Acupoint.

(1) Background: The medical practice of acupuncture involves the insertion of a specialized stainless needle into a specific body point, often called an acupoint, to initiate a perceived phenomenon of de-qi sensation. Therefore, the term "de-qi" describes bodily sensations experienced by the recipient during acupuncture, which may include feelings of soreness, heaviness, fullness, numbness, and migration. However, while acupuncture treatments reportedly result in acupoint activation and an increased release of neurotransmitters or cytokines, detecting these substances released into the acupoint microenvironment is often missed or delayed in clinical and basic practice. (2) Methods: To address this situation, we employed a paper-based enzyme-linked immunosorbent assay method to examine acupoint environmental changes using minute volumes of easily accessible acupoint fluids. (3) Results: Our results indicated that while levels of adenosine triphosphate (ATP), interleukin-1ß, interleukin-6, glutamate, substance P, and histamine were all increased in the experimental group following electroacupuncture (EA) treatment, contrary results were observed in the sham EA and transient receptor potential vanilloid 1 (Trpv1-/-) groups. Subsequently, TRPV1 and its associated molecules were augmented in mouse dorsal root ganglion, spinal cord, thalamus, and the somatosensory cortex, then examined by Western blotting and immunofluorescence techniques. Investigations revealed that these elevations were still unobserved in the sham EA or EA in the Trpv1-/- groups. Furthermore, results showed that while administering ATP could mimic EA function, it could be reversed by the ATP P2 receptor antagonist, suramin. (4) Conclusions: Our data provide novel information, indicating that changes in neurotransmitter and cytokine levels can offer insight into acupuncture mechanisms and clinical targeting.

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.

Optogenetic modulation of electroacupuncture analgesia in a mouse inflammatory pain model.

Peripheral tissue damage and associated inflammation can trigger neuroplastic changes in somatic pain pathways, such as reduced neuronal firing thresholds and synaptic potentiation, that ultimately lead to peripheral sensitization and chronic pain. Electroacupuncture (EA) can relieve chronic inflammatory pain, but the underlying mechanisms are unknown, including the contributions of higher pain centers such as somatosensory cortex (SSC). We investigated these mechanisms using optogenetic modulation of SSC activity in a mouse inflammatory pain model. Injection of Complete Freund's Adjuvant into the hind paw reliably induced inflammation accompanied by reduced mechanical and thermal pain thresholds (hyperalgesia) within three days (mechanical: 1.54 ± 0.13 g; thermal: 3.94 ± 0.43 s). Application of EA produced significant thermal and mechanical analgesia, but these responses were reversed by optogenetic activation of SSC neurons, suggesting that EA-induced analgesia involves modulation of central pain pathways. Western blot and immunostaining revealed that EA also attenuated CaMKIIα signaling in the dorsal root ganglion, central spinal cord, SSC, and anterior cingulate cortex (ACC). In contrast, optogenetic activation of the SSC induced CaMKIIα signaling in SSC and ACC. These findings suggest that AE can relieve inflammatory pain by suppressing CaMKIIα-dependent plasticity in cortical pain pathways. The SSC and ACC CaMKIIα signaling pathways may be valuable therapeutic targets for chronic inflammatory pain treatment.

Electroacupuncture Attenuates Chronic Inflammatory Pain and Depression Comorbidity through Transient Receptor Potential V1 in the Brain.

Chronic pain is one of the highest costs in clinical therapy, often appearing comorbid with depression. They present with overlapping clinical conditions and common pathological pathways especially in neuroinflammation, both of which can be reversed by electroacupuncture (EA). Transient receptor potential V1 receptor (TRPV1) is a Ca[Formula: see text] permeable ion channel that responds to brain inflammation and has a known role in the development of chronic pain and depression. Here, we investigate the role of TRPV1 and its related molecules in a mouse model of inflammation-induced chronic pain and depression using Complete Freund's adjuvant (CFA). We measured inflammatory mediators in plasma and evaluated the TRPV1 signaling pathway in the medial prefrontal cortex (mPFC), hypothalamus, and periaqueductal gray (PAG) of the mouse brain. Mechanical and thermal hyperalgesia as well as depressive-like behaviors were induced using the open field test and forced swimming test. Therapeutic effects were observed in EA and Trpv1[Formula: see text] mice in measures of chronic pain and depression. Inflammatory mediators induced by CFA injection were attenuated by EA and Trpv1 deletion. TRPV1 and downstream molecules were significantly decreased in the mPFC, hypothalamus, and PAG of mice, effects which were reversed by EA and Trpv1 knockout. We provide novel evidence that these inflammatory mediators modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for chronic pain and depression.

Electroacupuncture reduces cold stress-induced pain through microglial inactivation and transient receptor potential V1 in mice.

BACKGROUND: The treatment, and efficacy thereof, is considered to be inadequate with specificity to alleviation of Fibromyalgia and its associated pain. Fibromyalgia patients suffer from chronic and persistent widespread pain and generalized tenderness. Transient receptor potential V1 (TRPV1), which is reported as a Ca2+ permeable ion channel that can be activated by inflammation, is reported to be involved in the development of fibromyalgia pain. METHODS: The current study explored the TRPV1 channel functions as a noxious sensory input in mice cold stress model. It remains unknown whether electroacupuncture (EA) attenuates fibromyalgia pain or affects the TRPV1 pathway. RESULTS: We show that cold stress increases mechanical and thermal pain (day 7: mechanical: 1.69 ± 0.41 g; thermal: 4.68 ± 0.56 s), and that EA and Trpv1 deletion counter this increase. EA and Trpv1 deletion reduced the cold stress-induced increase in inflammatory mediators and TRPV1-related molecules in the hypothalamus, periaqueductal gray (PAG), and cerebellum of mice. CONCLUSIONS: Our results imply that EA has an analgesic effect associated with TRPV1 downregulation. We provide novel evidence that these inflammatory mediators can modulate the TRPV1 signaling pathway and suggest new potential therapeutic targets for fibromyalgia pain.

Acupuncture reduced the medical expenditure in migraine patients: Real-world data of a 10-year national cohort study.

OBJECTIVES: According to the data of Organisation for Economic Cooperation and Development, almost all the countries got increased medical expenditures in these years. Among the diseases, migraine is a condition that affects predominantly young and middle-aged people. It results in great economic losses. So we perform this research to investigate the acupuncture effect of reducing medical expenditure and medical resources use. PERSPECTIVE: Acupuncture is a non-pharmacologic treatment and it became popular in recent years. In Taiwan, about 13% migraine patients visited acupuncture doctor. We hypothesized that the acupuncture had the additional effect than the medical treatment. SETTING: We analysed the economic cost and medical visits in the real word. METHODS: We used national cohort data from Taiwan, retrospectively gathered between 2000 and 2010. We selected newly diagnosed migraine patients who were diagnosed by registered neurologists formally licensed by the Taiwan Neurological Society. We divided these patients into two groups: with and without acupuncture treatment. The main outcome was medical expenditures and visits within 1 year after acupuncture. RESULTS: In migraine patients who received acupuncture treatment, medical expenditures on emergency care and hospitalization were significantly lower than the group without acupuncture treatment. CONCLUSION: According to our real-world data, acupuncture can reduce the medical expenditure in migraine patients within 1 year after diagnosis. For the health policy maker, it is cost effective to encourage combining acupuncture and western medicine to treat migraine patients. For the doctors in routine clinical practice, who may consider to consult acupuncture doctors to deal with the migraine patients together.

Effects and Mechanisms of Electroacupuncture on Chronic Inflammatory Pain and Depression Comorbidity in Mice.

Comorbidity of chronic pain and major depression disorder (MDD) are common diseases. However, the mechanisms of electroacupuncture (EA) and the responses of N-methyl-D-aspartate receptors in the brain remain unclear. Three injections of complete Freund's adjuvant (CFA) were administered to induce chronic inflammatory pain (CIP). EA was then performed once every other day from days 14 to 28. Behavior tests of chronic pain and depression were evaluated to make sure of the successful induction of comorbidity. We used Western blotting to analyze brain tissue from the prefrontal cortex (PFC), hippocampus, and hypothalamus for levels of phosphorylated N-methyl-D-aspartate receptor subunit 1 (pNR1), NR1, pNR2B, NR2B, and calcium/calmodulin-dependent protein kinase type II alpha isoform (pCaMKIIα). The mechanical hyperalgesia, thermal hyperalgesia, and depression were observed in the CIP group. Furthermore, decreased levels of N-methyl-D-aspartate receptors (NMDARs) were also noted. Not Sham EA but EA reversed chronic pain and depression as well as the decreased levels of NMDA in the signaling pathway. The CFA injections successfully induced a significant comorbidity model. EA treated the comorbidity by upregulating the NMDA signaling pathway in the PFC, hippocampus, and hypothalamus. Our results indicated significant mechanisms of comorbidity of chronic pain and MDD and EA-analgesia that involves the regulation of the NMDAR signaling pathway. These findings may be relevant to the evaluation and treatment of comorbidity of chronic pain and MDD.

Chinese Herbal Medicine and Acupuncture Reduced the Risk of Stroke After Bell's Palsy: A Population-Based Retrospective Cohort Study.

Objectives: Patients with Bell's palsy are more likely to develop stroke than the general population. The therapeutic effect of Traditional Chinese Medicine (TCM) on the risk of stroke in patients with Bell's palsy is unknown. We investigated the risk of stroke according to TCM use in Bell's palsy patients. Design: Records obtained from Taiwan's National Health Insurance Research Database identified 9,863 patients with Bell's palsy, 238 of whom met study inclusion criteria and were categorized as TCM users (n = 119) or non-TCM users (n = 119). TCM treatment modalities and Chinese herbal medicine prescription patterns were analyzed. Cox proportional hazards regression analysis determined the risk of stroke. Results: TCM users were at lower risk of stroke compared with non-TCM users (adjusted hazard ratio [aHR] 0.19; 95% confidence interval [CI], 0.06-0.59; p < 0.004). In subgroup analyses, patients treated with both TCM and oral steroids were at significantly lower risk of stroke compared with those who used neither (aHR 0.05; 95% CI, 0.01-0.22; p < 0.001). The risk of stroke was also lower among those treated with TCM only (aHR 0.25; 95% CI, 0.11-0.59; p < 0.001) or oral steroids only (aHR 0.12; 95% CI, 0.03-0.39; p < 0.01), compared with patients using neither. Conclusion: TCM therapy may lower the risk of stroke after Bell's palsy. However, the retrospective nature of this study and characteristics of the database limit these observational findings. Our results deserve further verification in large-scale prospective studies.

Efficacy of laser acupuncture for patients with chronic Bell's palsy: A study protocol for a randomized, double-blind, sham-controlled pilot trial.

BACKGROUND: Bell's palsy is the most frequent cause of unilateral peripheral facial palsy, a common condition that third of patients can have inadequate recovery and subsequent physical and social impairments. The largely ineffective and even controversial nature of the various medical and surgical treatment options means that novel, alternative approaches are needed. In preclinical and clinical evidence, low-level laser therapy (LLLT) has demonstrated the ability to regenerate peripheral nerves. Laser acupuncture treatment (LAT), the stimulation of traditional acupoints with low-intensity, non-thermal laser irradiation, is a common treatment modality, but its efficacy in chronic Bell's palsy is undetermined. This study aims to evaluate the efficacy of LAT in patients experiencing inadequate recovery from Bell's palsy. METHODS: This 2-armed, parallel, randomized, subject-assessor-blinded, single-center, sham-controlled pilot trial will randomly assign 32 eligible patients into either a real LAT group (n = 16) or a sham LAT group (n = 16). The real LAT group will receive 3 LAT sessions each week for 6 weeks (a total of 18 sessions), delivered to acupoints corresponding with the affected side of the face. The sham LAT group will receive the same treatment as the real LAT group, but with a sham laser device. The primary outcome measure will be the change from baseline at week 6 in the Facial Disability Index score. Secondary outcomes will monitor changes during treatment in the House-Brackmann and Sunnybrook facial nerve grading systems and stiffness scale, at weeks 1, 3, and 6. DISCUSSION: To the best of our knowledge, this double-blind, randomized, sham-controlled trial is the first such investigation into the efficacy of LAT in chronic Bell's palsy. Clinical trials using LLLT have shown positive therapeutic effects in acute Bell's palsy, although as yet, the feasibility and efficacy of LAT remain unclear in patients experiencing inadequate recovery from Bell's palsy. TRIAL REGISTRATION: This trial protocol has been approved by the Research Ethics Committee of the China Medical University Hospital, Taichung, Taiwan (Protocol ID: CMUH107-REC1-030) also registered at ClinicalTrials.gov (identifier no. NCT03592797).

Electroacupuncture Attenuates Induction of Inflammatory Pain by Regulating Opioid and Adenosine Pathways in Mice.

Although inflammatory pain is a common clinical condition, its mechanisms are still unclear. Electroacupuncture (EA), a well-known method of pain management, may reduce inflammatory pain by regulating neurons, astrocytes, and inflammatory signaling pathways. Injections of complete Freund's adjuvant (CFA), which can initiate cell-mediated inflammatory pain, resulted in significant hyperalgesia, which was subsequently prevented by EA. In CFA-injected mice, a dramatic increase was observed in the expression of the following proteins in the dorsal root ganglion and spinal cord dorsal horn: the astrocytic marker GFAP, S100B, RAGE, pPKCε, COX-2, pERK, and pNFκB. These effects were reversed by EA. In addition, mechanical hyperalgesia was significantly reduced in the N6-cyclopentyladenosine (CPA) i.p. or i.m. and endomorphin (EM) i.p. groups. Neither EM i.m. nor EM i.p. exhibited any analgesic effect on thermal hyperalgesia. However, both CPA i.m. and CPA i.p. attenuated thermal hyperalgesia in the mouse inflammatory pain model. We showed that CPA reduced COX-2 and pPKCε expression. However, EM administration did not reduce COX-2 levels. Combined administration of naloxone and rolofylline increased pPKCε and COX-2 pathways. Taken together, our study results revealed a novel and detailed mechanism of EA-induced analgesia that involves the regulation of the opioid and adenosine pathways.

Clinical Evaluation of Acupuncture as Treatment for Complications of Cerebrovascular Accidents: A Randomized, Sham-Controlled, Subject- and Assessor-Blind Trial.

Background and Purpose. The effect of acupuncture as treatment for poststroke complications is questionable. We performed a randomized, sham-controlled double-blind study to investigate it. Methods. Patients with first-time acute stroke were randomized to receive 24 sessions of either real or sham acupuncture during an eight-week period. The primary outcome measure was change in National Institute of Health Stroke Scale (NIHSS) score. Secondary outcome measures included changes in Barthel Index (BI), Instrumental Activities of Daily Living (IADL), Hamilton Depression Rating Scale (HAM-D), and Visual Analogue Scale (VAS) for pain scores. Results. Of the 52 patients who were randomized to receive acupuncture (n = 28) or placebo (n = 24), 10 patients in the acupuncture group and 9 patients in the placebo group failed to complete the treatment. In total, 18 patients in the acupuncture group and 15 patients in the control group completed the treatment course. Reduction in pain was significantly greater in the acupuncture group than in the control group (p value = 0.04). There were no significant differences in the other measures between the two groups. Conclusions. Acupuncture provided more effective poststroke pain relief than sham acupuncture treatment. However, acupuncture had no better effect on neurological, functional, and psychological improvement.

Electroacupuncture Attenuates CFA-induced Inflammatory Pain by suppressing Nav1.8 through S100B, TRPV1, Opioid, and Adenosine Pathways in Mice.

Pain is associated with several conditions, such as inflammation, that result from altered peripheral nerve properties. Electroacupuncture (EA) is a common Chinese clinical medical technology used for pain management. Using an inflammatory pain mouse model, we investigated the effects of EA on the regulation of neurons, microglia, and related molecules. Complete Freund's adjuvant (CFA) injections produced a significant mechanical and thermal hyperalgesia that was reversed by EA or a transient receptor potential V1 (TRPV1) gene deletion. The expression of the astrocytic marker glial fibrillary acidic protein (GFAP), the microglial marker Iba-1, S100B, receptor for advanced glycation end-products (RAGE), TRPV1, and other related molecules was dramatically increased in the dorsal root ganglion (DRG) and spinal cord dorsal horn (SCDH) of CFA-treated mice. This effect was reversed by EA and TRPV1 gene deletion. In addition, endomorphin (EM) and N6-cyclopentyladenosine (CPA) administration reliably reduced mechanical and thermal hyperalgesia, thereby suggesting the involvement of opioid and adenosine receptors. Furthermore, blocking of opioid and adenosine A1 receptors reversed the analgesic effects of EA. Our study illustrates the substantial therapeutic effects of EA against inflammatory pain and provides a novel and detailed mechanism underlying EA-mediated analgesia via neuronal and non-neuronal pathways.