The Baimai Ointment with the effect of relaxing sinew and activating collaterals demonstrates a definite effect on Baimai disease with pain, spasm, stiffness and other symptoms, while the pharmacodynamic characteristics and mechanism of this agent remain unclear. In this study, a rat model of chronic compression of L4 dorsal root ganglion(CCD) was established by lumbar disc herniation, and the efficacy and mechanism of Baimai Ointment in the treatment of CCD were preliminarily explored by behavioral tests, side effect evaluation, network analysis, antagonist and molecular biology verification. The pharmacodynamic experiment indicated that Baimai Ointment significantly improved the pain thresholds(mechanical pain, thermal pain, and cold pain) and gait behavior of CCD model rats without causing tolerance or obvious toxic and side effects. Baimai Ointment inhibited the second-phase nociceptive response of mice in the formalin test, increased the hot plate threshold of normal mice, and down-regulated the expression of inflammatory cytokines in the spinal cord. Network analysis showed that Baimai Ointment had synergistic effect in the treatment of CCD and was related to descending inhibition/facilitation system and neuroinflammation. Furthermore, behavioral tests, Western blot, and immunofluorescence assay revealed that the pain-relieving effect of Baimai Ointment on CCD may be related to the regulation of the interaction between neuroactive ligand and receptors(neuroligands) such as CHRNA7, ADRA2A, and ADRB2, and the down-regulation of the expression of NOS2/pERK/PI3K, the core regulatory element of HIF-1 signaling pathway in spinal microglia. The findings preliminarily reveal the mechanism of relaxing sinew and activating collaterals of Baimai Ointment in the treatment of Baimai disease, providing a reference for the rational drug use and further research of this agent.
Rats ; Mice ; Animals ; Chronic Pain/metabolism* ; Rats, Sprague-Dawley ; Ganglia, Spinal/metabolism* ; Ligands ; Signal Transduction ; Hyperalgesia/metabolism* ; Drugs, Chinese Herbal

This study aimed to investigate the impact of the coronavirus disease 2019 (COVID-19) pandemic on erectile function in Chinese patients with chronic prostatitis/chronic pelvic pain syndrome (CP/CPPS). A retrospective study was conducted on 657 CP/CPPS patients who visited The Third Xiangya Hospital of Central South University (Changsha, China) from November 2018 to November 2022. Patients were divided into two groups based on the timeline before and after the COVID-19 outbreak in China. The severity of CP/CPPS, penile erection status, anxiety, and depression was evaluated using the National Institutes of Health-Chronic Prostatitis Symptom Index (NIH-CPSI), International Index of Erectile Function-5 (IIEF-5), Generalized Anxiety Disorder-7 (GAD-7), and Patient Health Questionnaire-9 (PHQ-9) scales, respectively. Compared with patients before the COVID-19 outbreak, more CP/CPPS patients developed severe erectile dysfunction (ED) due to depression and anxiety caused by the pandemic. After developing moderate-to-severe ED, mild and moderate-to-severe CP/CPPS patients exhibited more apparent symptoms of anxiety and depression ( P < 0.001 and P = 0.001, respectively), forming a vicious cycle. The COVID-19 pandemic has adversely affected the psychological status of CP/CPPS patients, exacerbating their clinical symptoms and complicating ED. The exacerbation of clinical symptoms further worsens the anxiety and depression status of patients, forming a vicious cycle. During the COVID-19 pandemic, paying more attention to the mental health of CP/CPPS patients, strengthening psychological interventions, and achieving better treatment outcomes are necessary.
Male ; Humans ; Erectile Dysfunction/etiology* ; Pandemics ; Penile Erection ; Prostatitis/complications* ; Retrospective Studies ; East Asian People ; COVID-19/complications* ; Chronic Disease ; Pelvic Pain/complications*

Humans ; Chronic Pain ; Analgesics, Opioid ; Pain Management ; Primary Health Care

The paper summarizes professor ZHANG Wei-hua's clinical experience for the treatment of chronic somatic pain with zhidong needling techniques. In terms of the characteristics of chronic somatic pain, professor ZHANG has integrated zhidong needling with acupuncture kinetic therapy. The satisfactory therapeutic effects are obtained by selecting the painful points and regions as the treatment sites and the specific techniques of zhidong needling depending on the size of affected area, the depth of illness, the size and shape of the cord-like muscle, etc. Five techniques of zhidong needling are used accordingly with twirling, pulling, lifting and thrusting, surrounding needling methods involved, as well as with the manipulation speed, direction and frequency considered.
Humans ; Vascular Surgical Procedures ; Chronic Pain ; Nociceptive Pain ; Acupuncture Therapy ; Muscles

Post-amputation pain causes great suffering to amputees, but still no effective drugs are available due to its elusive mechanisms. Our previous clinical studies found that surgical removal or radiofrequency treatment of the neuroma at the axotomized nerve stump effectively relieves the phantom pain afflicting patients after amputation. This indicated an essential role of the residual nerve stump in the formation of chronic post-amputation pain (CPAP). However, the molecular mechanism by which the residual nerve stump or neuroma is involved and regulates CPAP is still a mystery. In this study, we found that nociceptors expressed the mechanosensitive ion channel TMEM63A and macrophages infiltrated into the dorsal root ganglion (DRG) neurons worked synergistically to promote CPAP. Histology and qRT-PCR showed that TMEM63A was mainly expressed in mechanical pain-producing non-peptidergic nociceptors in the DRG, and the expression of TMEM63A increased significantly both in the neuroma from amputated patients and the DRG in a mouse model of tibial nerve transfer (TNT). Behavioral tests showed that the mechanical, heat, and cold sensitivity were not affected in the Tmem63a^-/- mice in the naïve state, suggesting the basal pain was not affected. In the inflammatory and post-amputation state, the mechanical allodynia but not the heat hyperalgesia or cold allodynia was significantly decreased in Tmem63a^-/- mice. Further study showed that there was severe neuronal injury and macrophage infiltration in the DRG, tibial nerve, residual stump, and the neuroma-like structure of the TNT mouse model, Consistent with this, expression of the pro-inflammatory cytokines TNF-α, IL-6, and IL-1β all increased dramatically in the DRG. Interestingly, the deletion of Tmem63a significantly reduced the macrophage infiltration in the DRG but not in the tibial nerve stump. Furthermore, the ablation of macrophages significantly reduced both the expression of Tmem63a and the mechanical allodynia in the TNT mouse model, indicating an interaction between nociceptors and macrophages, and that these two factors gang up together to regulate the formation of CPAP. This provides a new insight into the mechanisms underlying CPAP and potential drug targets its treatment.
Animals ; Mice ; Amputation, Surgical ; Chronic Pain/pathology* ; Disease Models, Animal ; Ganglia, Spinal/pathology* ; Hyperalgesia/etiology* ; Ion Channels/metabolism* ; Macrophages ; Neuroma/pathology*

Chronic pain relief remains an unmet medical need. Current research points to a substantial contribution of glia-neuron interaction in its pathogenesis. Particularly, microglia play a crucial role in the development of chronic pain. To better understand the microglial contribution to chronic pain, specific regional and temporal manipulations of microglia are necessary. Recently, two new approaches have emerged that meet these demands. Chemogenetic tools allow the expression of designer receptors exclusively activated by designer drugs (DREADDs) specifically in microglia. Similarly, optogenetic tools allow for microglial manipulation via the activation of artificially expressed, light-sensitive proteins. Chemo- and optogenetic manipulations of microglia in vivo are powerful in interrogating microglial function in chronic pain. This review summarizes these emerging tools in studying the role of microglia in chronic pain and highlights their potential applications in microglia-related neurological disorders.
Humans ; Optogenetics ; Brain/physiology* ; Microglia ; Chronic Pain/therapy* ; Neurons/physiology*

Chronic pain is challenging to treat due to the limited therapeutic options and adverse side-effects of therapies. Astrocytes are the most abundant glial cells in the central nervous system and play important roles in different pathological conditions, including chronic pain. Astrocytes regulate nociceptive synaptic transmission and network function via neuron-glia and glia-glia interactions to exaggerate pain signals under chronic pain conditions. It is also becoming clear that astrocytes play active roles in brain regions important for the emotional and memory-related aspects of chronic pain. Therefore, this review presents our current understanding of the roles of astrocytes in chronic pain, how they regulate nociceptive responses, and their cellular and molecular mechanisms of action.
Humans ; Astrocytes/pathology* ; Chronic Pain/pathology* ; Neuroglia/physiology* ; Neurons/physiology* ; Synaptic Transmission ; Chronic Disease

The article presents an original method for the automatic assessment of the quality of event-related potentials (ERPs), based on the calculation of the coefficient ε, which describes the compliance of recorded ERPs with some statistically significant parameters. This method was used to analyze the neuropsychological EEG monitoring of patients suffering from migraines. The frequency of migraine attacks was correlated with the spatial distribution of the coefficients ε, calculated for EEG channels. More than 15 migraine attacks per month was accompanied by an increase in calculated values in the occipital region. Patients with infrequent migraines exhibited maximum quality in the frontal areas. The automatic analysis of spatial maps of the coefficient ε demonstrated a statistically significant difference between the two analyzed groups with different means of migraine attack numbers per month.
Humans ; Chronic Pain ; Evoked Potentials ; Migraine Disorders/psychology* ; Occipital Lobe ; Electroencephalography

Objective: To analyze the therapeutic effect and safety of pancreatic extracorporeal shock wave lithotripsy(P-ESWL) for patients with chronic pancreatitis complicated by stones of the pancreatic duct and to investigate the influencing factors. Methods: A retrospective analysis was performed on clinical data from 81 patients with chronic pancreatitis complicated by pancreatic duct calculus treated with P-ESWL in the Department of Hepatobiliary Surgery, the First Affiliated Hospital of Xi 'an Jiaotong University from July 2019 to May 2022. There were 55 males(67.9%) and 26 females(32.1%). The age was (47±15)years (range: 17 to 77 years). The maximum diameter(M(IQR)) of the stone was 11.64(7.60) mm, and the CT value of the stone was 869 (571) HU. There were 32 patients (39.5%) with a single pancreatic duct stone and 49 patients(60.5%) with multiple pancreatic duct stones. The effectiveness, remission rate of abdominal pain, and complications of P-ESWL were evaluated. Student's t test, Mann Whitney U test, χ² test, or Fisher's exact test was used to compare the characteristics between the effective and ineffective groups of lithotripsy. The factors influencing the effect of lithotripsy were analyzed by univariate and multivariate logistic regression analysis. Results: Eighty-one patients with chronic pancreatitis were treated with P-ESWL 144 times, with an average of 1.78 (95%CI:1.60 to 1.96) times per person. Among them, 38 patients(46.9%) were treated with endoscopy. There were 64 cases(79.0%) with effective removal of pancreatic duct calculi and 17 cases(21.0%) with ineffective removal. Of the 61 patients with chronic pancreatitis accompanied by abdominal pain, 52 cases(85.2%) had pain relief after lithotripsy. After lithotripsy treatment, 45 patients(55.6%) developed skin ecchymosis, 23 patients(28.4%) had sinus bradycardia, 3 patients(3.7%) had acute pancreatitis, 1 patient(1.2%) had a stone lesion, and 1 patient(1.2%) had a hepatic hematoma. Univariate and multivariate logistic regression analysis showed that the factors affecting the efficacy of lithotripsy included the age of patient(OR=0.92, 95%CI: 0.86 to 0.97), the maximum diameter of the stone(OR=1.12,95%CI:1.02 to 1.24) and the CT value of the stone(OR=1.44, 95%CI: 1.17 to 1.86). Conclusions: P-ESWL is effective in the treatment of patients with chronic pancreatitis complicated by calculi of the main pancreatic duct.Factors affecting the efficacy of lithotripsy include patient's age, maximum stone diameter, and CT value of calculi.
Male ; Female ; Humans ; Retrospective Studies ; Acute Disease ; Treatment Outcome ; Calculi/pathology* ; Lithotripsy ; Pancreatitis, Chronic/pathology* ; Pancreatic Diseases/complications* ; Pancreatic Ducts ; Abdominal Pain/therapy*

OBJECTIVE: To observe the clinical effect of electroacupuncture (EA) for acute exacerbation of chronic obstructive pulmonary disease (AECOPD) complicated with gastrointestinal dysfunction. METHODS: A total of 100 patients with AECOPD complicated with gastrointestinal dysfunction were randomly divided into an EA group (50 cases, 2 cases dropped off, 1 case excluded) and a medication group (50 cases). Both groups were treated with symptomatic and supportive treatment such as low flow oxygen, nebulized inhalation of short-acting β2 agonist (SABA) or short-acting muscarinic antagonist (SAMA) combined with inhaled corticosteroid (ICS). The EA group was treated with EA at Zusanli (ST 36), Yinlingquan (SP 9), Zhongwan (CV 12), Shuifen (CV 9), Tianshu (ST 25), Chize (LU 5) and Lieque (LU 7), with discontinuous wave, 2 Hz in frequency, 30 min each time, once a day. In the medication group, oral mosapride citrate tablets were given, 3 times a day, 5 mg each time. Both groups were treated for 5 d. Before and after treatment, the gastrointestinal symptom rating scale (GSRS) score was observe, serum procalcitonin (PCT), C-reactive protein (CRP), and plasma oxygenation index (PaO₂/FiO₂) were detected, and patient satisfaction degree was evaluated in the two groups. RESULTS: Compared with before treatment, except for diarrhea dimension in the medication group, the total scores and each dimension scores of GSRS were decreased (P<0.05), serum PCT and CRP were decreased (P<0.05), plasma PaO₂/FiO₂ was increased (P<0.05) in the two groups after treatment. After treatment, in the EA group, the total score and abdominal pain, dyspepsia, constipation and diarrhea scores of GSRS were lower than those in the medication group (P<0.05), meanwhile serum PCT and CRP were lower and plasma PaO₂/FiO₂ was higher than those in the medication group (P<0.05). The improvement of gastrointestinal symptoms, life quality and overall satisfaction degree in the EA group were superior to those in the medication group (P<0.05). CONCLUSION EA could improve the symptoms of patients with AECOPD complicated with gastrointestinal dysfunction, reduce inflammatory response, improve oxygenation and patient satisfaction degree.
Humans ; Electroacupuncture ; Gastrointestinal Diseases/therapy* ; Pulmonary Disease, Chronic Obstructive/therapy* ; Diarrhea ; Abdominal Pain ; C-Reactive Protein