1.Role and mechanisms of interneurons in chronic pain and pain-induced cognitive impairment.
Qi WANG ; Guangfen ZHANG ; Bo WANG
Journal of Central South University(Medical Sciences) 2025;50(4):625-630
Chronic pain, a prevalent chronic disease, frequently manifests not only in physical symptoms but also in cognitive impairment, which seriously affects patients' quality of life. Interneurons are multipolar neurons, most of which are inhibitory, serving as crucial connectors within neural networks. They play key roles in signal transmission and fine-tuning of neural activity. In recent years, growing evidence has shown that interneurons are involved in the development of chronic pain and its associated cognitive dysfunction. Investigating the relationship between interneuron dysfunction and chronic pain-related cognitive impairment is of great significance, offering new potential targets and insights for the development of novel therapeutic approaches.
Interneurons/physiology*
;
Humans
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Chronic Pain/complications*
;
Cognitive Dysfunction/physiopathology*
;
Cognition Disorders/physiopathology*
;
Animals
2.Chemokine CCL2 Mediates Neuroglial Crosstalk and Drives Chronic Pain Pathogenesis.
Junyu LU ; Yunxin SHI ; Yongkang LI ; Ziyi NIU ; Shengxi WU ; Ceng LUO ; Rou-Gang XIE
Neuroscience Bulletin 2025;41(12):2296-2321
Chronic pain, frequently comorbid with neuropsychiatric disorders, significantly impairs patients' quality of life and functional capacity. Accumulating evidence implicates the chemokine CCL2 and its receptor CCR2 as key players in chronic pain pathogenesis. This review examines the regulatory mechanisms of the CCL2/CCR2 axis in chronic pain processing at three hierarchical levels: (1) Peripheral Sensitization: CCL2/CCR2 modulates TRPV1, Nav1.8, and HCN2 channels to increase neuronal excitability and CGRP signaling and calcium-dependent exocytosis in peripheral nociceptors to transmit pain. (2) Spinal Cord Central Sensitization: CCL2/CCR2 contributes to NMDAR-dependent plasticity, glial activation, GABAergic disinhibition, and opioid receptor desensitization. (3) Supraspinal Central Networks: CCL2/CCR2 signaling axis mediates the comorbidity mechanisms of pain with anxiety and cognitive impairment within brain regions, including the ACC, CeA, NAc, and hippocampus, and it also increases pain sensitization through the descending facilitation system. Current CCL2/CCR2-targeted therapeutic strategies and their development status are discussed, highlighting novel avenues for chronic pain management.
Humans
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Chronic Pain/physiopathology*
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Animals
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Neuroglia/metabolism*
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Chemokine CCL2/metabolism*
;
Receptors, CCR2/metabolism*
3.Reduced zinc concentration in expressed prostatic secretion relates to the pain symptoms of types Ⅲ and Ⅳ prostatitis.
Lin-Jian MO ; Xi CHEN ; Xiao-Ming WANG ; Guang-Yu LI ; Xun ZHANG ; Shan HUANG ; Zhi-Bin XIE ; Zeng-Nan MO
National Journal of Andrology 2016;22(6):496-500
ObjectiveTo determine the zinc levels in the expressed prostatic secretion (EPS) of the patients with different types of chronic nonbacterial prostatitis, and explore the reference value of zinc concentration in EPS in the diagnosis and treatment of prostatitis.
METHODSWe collected EPS samples from 35 healthy men and 173 patients with chronic nonbacterial prostatitis, including 65 cases of type ⅢA, 69 cases of type ⅢB, and 39 cases of type Ⅳ, according to the National Institutes of Health Chronic Prostatitis Symptom Index (NIH-CPSI). We compared the zinc levels in the EPS samples among different groups and analyzed the correlations of zinc concentration with the NIH-CPSI scores, WBC count, pH value, and age of the subjects.
RESULTSThe participants were aged 17-65 (32.5±8.5) years. The zinc concentrations in the EPS were significantly lower in the ⅢA ([162.2±10.8] μg/ml) and ⅢB ([171.2±12.0] μg/ml) than in the Ⅳ ([234.6±17.9] μg/ml) (P<0.05 ) and the control group ([259.5±14.6] μg/ml) (P<0.05 ). The zinc level was correlated negatively with the NIH-CPSI pain score (r=-0.248, P<0.01), quality of life score (r=-0.232, P<0.01), severity score (r=-0.270, P<0.01), total NIH-CPSI score (r=-0.281, P<0.01), and the pH value in EPS (r=-0.208, P<0.01), but showed no correlation with the WBC count and age of the subjects.
CONCLUSIONSThe reduced zinc concentration in the EPS of the patients with chronic nonbacterial prostatitis may be associated with the pain symptoms of the disease, which suggests the potential reference value of measuring the zinc concentration in EPS in the diagnosis and treatment of prostatitis.
Adolescent ; Adult ; Aged ; Chronic Disease ; Humans ; Male ; Middle Aged ; Pain ; metabolism ; Prostatitis ; metabolism ; physiopathology ; Quality of Life ; Young Adult ; Zinc ; metabolism
4.Kinematic effect of Chinese herbal fomentation on patients with chronic neck pain.
Zhen-Yu LIU ; Bao-Ge LIU ; Xin LIN
Chinese journal of integrative medicine 2014;20(12):917-922
OBJECTIVETo clarify the effectiveness of Chinese herbal fomentation in treating chronic neck pain by means of changes in cervical kinematics.
METHODSSeventy-six patients with chronic neck pain were included in the study and were randomized into two groups based on the random number generator of the SPSS software: fomentation combined with Chinese herbal (Group 1) and fomentation without any medicine (Group 2). In both groups, the fomentation lasted for 60 min and heated to 35 °C, once a day for 28 consecutive days. Standard lateral radiographs of the cervical spine were obtained including the neutral, full flexion, and full extension positions. Before and after intervention, the following parameters were used to evaluate the changes in kinematics: range of motion (ROM), sagittal alignment and instantaneous center of rotation (ICR).
RESULTSAfter treatment, the ROM was signifcantly higher than that of before treatment in Group 1 (51.5, 95% CI: 49.8-55.9; P<0.05). There was no significant difference between before and after treatment in Group 2 (P>0.05). Although C2-C7 cervical alignment was increased in both groups after treatment, no significant difference was detected between before and after treatment (P>0.05). For Group 1, the significant X coordinate variation was only observed at C5/C6 level (38.1; 95% CI: 34.0, 42.1; P<0.05). There was a significant upward trend in the Y coordinate of the ICR at C5/C6 (-30.5; 95% CI: -34.3, -26.8; P<0.05) and C6/C7 after treatment (-6.1; 95% CI: -6.7, -5.4; P<0.05). For Group 2, the ICR location of each level was not statistically different between the pre- and post-treatment (P>0.05).
CONCLUSIONSChinese herbal fomentation could improve abnormal mobility in terms of ROM and ICR. Chinese herbal fomentation might be an effective treatment for chronic neck pain.
Adult ; Biomechanical Phenomena ; Cervical Vertebrae ; diagnostic imaging ; physiopathology ; Chronic Pain ; diagnostic imaging ; drug therapy ; physiopathology ; Drugs, Chinese Herbal ; therapeutic use ; Female ; Humans ; Male ; Neck Pain ; diagnostic imaging ; drug therapy ; physiopathology ; Radiography ; Range of Motion, Articular
5.Clinical and Radiological Predictive Factors to be Related with the Degree of Lumbar Back Muscle Degeneration: Difference by Gender.
Woo Dong NAM ; Bong Soon CHANG ; Choon Ki LEE ; Jae Hwan CHO
Clinics in Orthopedic Surgery 2014;6(3):318-323
BACKGROUND: The prediction of lumbar back muscle degeneration is important because chronic low back pain and spino-pelvic imbalance have been known to be related to it. However, gender difference should be considered because there are different quality and volume of muscles between genders. The purpose of this study was to search for clinical and radiological factors to predict the degree of lumbar back muscle degeneration according to gender difference. METHODS: We reviewed 112 patients (44 men and 68 women) with spinal stenosis who underwent a decompressive surgery between 1 January 2009 and 31 December 2011. Degrees of lumbar back muscle degeneration were classified into three categories by the fatty infiltration at each L3-4 disc level on the axial view of T1 magnetic resonance imaging (MRI). Age, sex, bone marrow density score, and body mass index (BMI) were obtained from chart reviews. Lumbar lordosis, sacral slope, pelvic tilt (PT), and pelvic incidence were calculated with lumbar spine standing lateral radiographs. The degrees of spinal stenosis and facet arthropathy were checked with MRI. Student t-test, chi-square test, or Fisher exact test were used to compare clinical and radiological parameters between genders. Analysis of variance (ANOVA) and linear regression analysis were used to search for a relationship between lumbar back muscle degeneration and possible predictive factors in each gender group. RESULTS: Many clinical and radiological parameters were different according to gender. The age, BMI, and PT in the female group (p = 0.013, 0.001, and 0.019, respectively) and the PT in the men group (p = 0.018) were predictive factors to be correlated with lumbar back muscle degeneration. CONCLUSIONS: The PT was the important predictive factor for lumbar back muscle degeneration in both, the male and the female group. However, age and BMI were predictive factors in the female group only.
Aged
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Back Muscles/*pathology/physiopathology/radiography
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Chronic Disease
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Decompression, Surgical
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Female
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Humans
;
Low Back Pain/*diagnosis/physiopathology/surgery
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Lumbosacral Region
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Magnetic Resonance Imaging
;
Male
;
Middle Aged
;
Postural Balance
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Posture
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Predictive Value of Tests
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Retrospective Studies
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Spinal Stenosis/*diagnosis/physiopathology/surgery
6.Radial shock wave therapy in the treatment of chronic constriction injury model in rats: a preliminary study.
Miao FU ; Hao CHENG ; Duoyi LI ; Xiaotong YU ; Nan JI ; Fang LUO
Chinese Medical Journal 2014;127(5):830-834
BACKGROUNDPain physicians pay close attention to neuropathic pain (NP), since there is currently no ideal treatment. Radial shock wave therapy (RSWT) is a noninvasive treatment to chronic pain of soft tissue disorders. So far, there is no information on the use of RSWT for the treatment of NP. Therefore we observe the effects of RSWT on a NP model induced by chronic constriction injury (CCI) in rats.
METHODSFour different energy densities (1.0, 1.5, 2.0 and 2.5 bar) RSWT administered as a single session or repeated sessions in rats with NP induced by CCI of the sciatic nerve. The analgesic effect was assessed by measuring mechanical withdrawal threshold (MWT) and thermal withdrawal latency (TWL). The safety was assessed through calculating sciatic functional index (SFI).
RESULTSMWT and TWL increased after a single session of RSWT from day 1 to day 5 but returned to baseline levels by day 10. Following repeated sessions of RSWT, both the MWT and TWL were significantly higher than NP group (P < 0.01) for at least 4 weeks. In addition, no significant changes of SFI were observed in any groups after repeated sessions of RSWT and no increased pain or other side effects in any animals.
CONCLUSIONSA single session of RSWT is rapidly effective in the treatment of CCI, but the efficacy maintained in a short period. However, repeated sessions of RSWT have prolonged efficacy.
Animals ; Chronic Pain ; therapy ; High-Energy Shock Waves ; Male ; Neuralgia ; therapy ; Rats, Sprague-Dawley ; Sciatic Nerve ; physiopathology
7.Hypnotherapy: a forgotten modality in managing chronic post-traumatic upper limb pain.
Peter MACK ; Andrew K T YAM ; Andrew Y H CHIN
Annals of the Academy of Medicine, Singapore 2013;42(7):361-362
Amputation
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adverse effects
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Amputation Stumps
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physiopathology
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surgery
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Analgesics
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administration & dosage
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Chronic Pain
;
etiology
;
physiopathology
;
therapy
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Combined Modality Therapy
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Female
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Humans
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Hypnosis
;
methods
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Middle Aged
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Pain Management
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Phantom Limb
;
etiology
;
physiopathology
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therapy
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Reoperation
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Treatment Outcome
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Upper Extremity
;
injuries
;
surgery
8.Altered thermal sensitivity in facial skin in chronic whiplash-associated disorders.
Birgitta HÄGGMAN-HENRIKSON ; Ewa LAMPA ; Erik NORDH
International Journal of Oral Science 2013;5(3):150-154
There is a close functional relationship between the jaw and neck regions and it has been suggested that trigeminal sensory impairment can follow whiplash injury. Inclusion of manageable routines for valid assessment of the facial sensory capacity is thus needed for comprehensive evaluations of patients exposed to such trauma. The present study investigated facial thermal thresholds in patients with chronic whiplash-associated disorders (WADs) with both a qualitative method and quantitative sensory testing (QST). Ten women with pain and dysfunction following a whiplash injury were compared to 10 healthy age-matched women. Thermal detection thresholds were assessed by qualitative chair-side testing and by QST according to the method-of-limits. Seven test sites in the facial skin (overlying each trigeminal branch bilaterally, and the midpoint of the chin) were examined. The detection warm and cold thresholds were defined as the mean values of 10 individual thresholds. For the WAD patients, the qualitative assessment demonstrated both reduced and increased sensitivity compared to the healthy, whereas QST systematically showed significantly higher detection thresholds (i.e., decreased sensitivity) for both cold and warm stimuli. For the individuals who were assessed as having increased sensitivity in the qualitative assessment, the QST displayed either normal or higher thresholds, i.e., decreased sensitivity. The results suggest that QST is more sensitive for detecting thermal sensory disturbances in the face than a qualitative method. The impaired thermal sensitivity among the patients corroborates the notion of altered thermal detection capacity induced by WAD-related pain.
Case-Control Studies
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Chronic Disease
;
Evaluation Studies as Topic
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Facial Pain
;
etiology
;
physiopathology
;
Female
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Humans
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Neck Pain
;
etiology
;
physiopathology
;
Sensory Thresholds
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Skin
;
physiopathology
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Statistics, Nonparametric
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Thermosensing
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Trigeminal Nerve Injuries
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complications
;
physiopathology
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Whiplash Injuries
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complications
;
physiopathology
9.Psychometrics of the chronic liver disease questionnaire for patients with posthepatitic B cirrhosis.
Xin-cai HU ; Hua ZHANG ; Yan LIN ; Yang ZHOU ; Ping LIU
Chinese Journal of Hepatology 2012;20(8):621-627
To report on the validity and reliability of the Chronic Liver Disease Questionnaire (CLDQ) for assessing subjects with posthepatitic B cirrhosis. The CLDQ was administered to 117 healthy volunteers and 297 patients with posthepatitic B cirrhosis. All posthepatic B cirrhosis patients were assessed for the Child-Pugh stage. The entire questionnaire and each individual item was analyzed for precision and reliability. Exploratory factor analysis, responsiveness, and discrimination validity were also assessed. No significant floor effects were detected, but a moderate ceiling effect (less than 30%) was found for the following subscales: abdominal symptoms (AS), activity (AC), and worry (WO). For most items, the ceiling effect was between 30% to 60%. The internal consistency (Cronbach's a) on total scale level was good (a = 0.905), and ranged from 0.442 to 0.848 for the different subscales. The correlation coefficients of the total scale with subscales were above 0.6 (P less than 0.01) for reliability. The CLDQ and subscale scores for healthy controls were higher than those for the patients (P less than 0.001), and were gradated from the patients with Child-Pugh A cirrhosis to those with Child-Pugh B or C cirrhosis. Increase in severity of liver disease was accompanied by lower scores by the CLDQ and 4 out 6 subscales. Exploratory factor analysis moderately reproduced the original factor structure. The CLDQ has good reliability, satisfactory content, responsiveness and discriminant validity, and moderate precision and construct validity. It is useful for effectively evaluating health-related quality of life and curative effect in patients with posthepatitic B cirrhosis.
Adolescent
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Adult
;
Aged
;
Case-Control Studies
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Chronic Disease
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Female
;
Health Status
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Hepatitis B, Chronic
;
psychology
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Humans
;
Liver Cirrhosis
;
psychology
;
Male
;
Middle Aged
;
Pain
;
physiopathology
;
psychology
;
Psychometrics
;
Quality of Life
;
psychology
;
Reproducibility of Results
;
Sensitivity and Specificity
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Severity of Illness Index
;
Statistics as Topic
;
Surveys and Questionnaires
;
Young Adult
10.Intra-articular Lesions in Chronic Lateral Ankle Instability: Comparison of Arthroscopy with Magnetic Resonance Imaging Findings.
Seung Do CHA ; Hyoung Soo KIM ; Soo Tai CHUNG ; Jeong Hyun YOO ; Jai Hyung PARK ; Joo Hak KIM ; Jae Won HYUNG
Clinics in Orthopedic Surgery 2012;4(4):293-299
BACKGROUND: Chronic lateral ankle instability often accompanies intra-articular lesions, and arthroscopy is often useful in diagnosis and treatment of intra-articular lesions. METHODS: Preoperative magnetic resonance imaging (MRI) examinations and arthroscopic findings were reviewed retrospectively and compared in 65 patients who underwent surgery for chronic lateral ankle instability from January 2006 to January 2010. MR images obtained were assessed by two radiologists, and the inter- and intra-observer reliability was calculated. American Orthopedic Foot and Ankle Society (AOFAS) and visual analogue scale (VAS) scores were evaluated. RESULTS: Abnormalities of the anterior talofibular ligament (ATFL) were found in all 65 (100%) cases. In arthroscopy examinations, 33 (51%) cases had talar cartilage lesions, and 3 (5%) cases had 'tram-track' cartilage lesion. Additionally, 39 (60%) cases of synovitis, 9 (14%) cases of anterior impingement syndrome caused by osteophyte, 14 (22%) cases of impingement syndrome caused by fibrotic band and tissue were found. Sensitivity of MRI examination for each abnormality was: ATFL, 60%; osteochondral lesion of talus (OLT), 46%; syndesmosis injury, 21%; synovitis, 21%; anterior impingement syndrome caused by osteophyte, 22%. Paired intra-observer reliability was measured by a kappa statistic of 0.787 (95% confidence interval [CI], 0.641 to 0.864) for ATFL injury, 0.818 (95% CI, 0.743 to 0.908) for OLT, 0.713 (95% CI, 0.605 to 0.821) for synovitis, and 0.739 (95% CI, 0.642 to 0.817) for impingement. Paired inter-observer reliability was measured by a kappa statistic of 0.381 (95% CI, 0.241 to 0.463) for ATFL injury, 0.613 (95% CI, 0.541 to 0.721) for OLT, 0.324 (95% CI, 0.217 to 0.441) for synovitis, and 0.394 (95% CI, 0.249 to 0.471) for impingement. Mean AOFAS score increased from 64.5 to 87.92 (p < 0.001) when there was no intra-articular lesion, from 61.07 to 89.04 (p < 0.001) in patients who had one intra-articular lesion, and from 61.12 to 87.6 (p < 0.001) in patients who had more than two intra-articular lesions. CONCLUSIONS: Although intra-articular lesion in patients with chronic lateral ankle instability is usually diagnosed with MRI, its sensitivity and inter-observer reliability are low. Therefore, arthroscopic examination is strongly recommended because it improved patients' residual symptoms and significantly increased patient satisfaction.
Ankle Joint/*pathology/*physiopathology
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Arthroscopy/methods
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Chronic Disease
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Female
;
Humans
;
Joint Diseases/*diagnosis/pathology
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Joint Instability/*diagnosis/pathology
;
Lateral Ligament, Ankle/pathology
;
Magnetic Resonance Imaging/methods
;
Male
;
Observer Variation
;
Pain Measurement
;
Retrospective Studies
;
Severity of Illness Index
;
Synovitis/pathology

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