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neuropathic pain-like symptoms and pre-surgery radiographic severity contribute to patient satisfaction 4.8 years post-total joint replacement

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World Journal of Orthopedics 2017年第10期8卷 761-769页

作者： Sophie C Warner Helen Richardson Wendy Jenkins Thomas Kurien Michael Doherty Ana M Valdes Academic Rheumatology University of NottinghamClinical Sciences BuildingNottingham City Hospital Department of Cardiovascular Sciences University of Leicester and National Institute for Health Res-earchLeicester Cardiovascular Biomedical Research Unit Arthritis Research UK Pain Centre Academic Division of Trauma and Orthopaedics Queens Medical Centre

AIM To investigate a comprehensive range of factors that contribute to long-term patient satisfaction post-total joint replacement(TJR) in people who had undergone knee or hip replacement for osteoarthritis.METHODS Participants(n = 1151) were recruited from Nottinghamshire post-total hip or knee replacement. Questionnaire assessment included medication use, the pain-DETECT questionnaire(PDQ) to assess neuropathic pain-like symptoms(NP) and TJR satisfaction measured on average 4.8 years post-TJR. Individual factors were tested for an association with post-TJR satisfaction, before incorporating all factors into a full model. Data reduction was carried out using LASSO and receiveroperator characteristic(ROC) curve analysis was used to quantify the contribution of variables to post-TJR satisfaction.RESULTS After data reduction, the best fitting model for post-TJR satisfaction included various measures of pain, history of revision surgery, smoking, pre-surgical X-ray severity, WOMAC function scores and various comorbidities. ROC analysis of this model gave AUC = 0.83(95%CI: 0.80-0.85). PDQ scores were found to capture much of the variation in post-TJR satisfaction outcomes: AUC = 0.79(0.75-0.82). Pre-surgical radiographic severity was associated with higher post-TJR satisfaction: OR_(satisfied) = 2.06(95%CI: 1.15-3.69), P = 0.015.CONCLUSION These results highlight the importance of pre-surgical radiographic severity, post-TJR function, analgesic medication use and NP in terms of post-TJR satisfaction. The PDQ appears to be a useful tool in capturing factors that contribute to post-TJR satisfaction.

关键词： Osteoarthritis Patient satisfaction Total joint arthroplasty neuropathic pain Surgery outcomes

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Pulsed radiofrequency inhibits expression of P2X3 receptors and alleviates neuropathic pain induced by chronic constriction injury in rats

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Chinese Medical Journal 2019年第14期132卷 1706-1712页

作者： Miao Fu Lan Meng Hao Ren Fang Luo Department of Anesthesiology Key Laboratory of Carcinogenesis and Translational Research(Ministry of Education)Peking University Cancer Hospital and InstituteBeijing 100142China Department of Pain Management Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China Department of Anesthesiology and Pain Management Beijing Tiantan HospitalCapital Medical UniversityBeijing 100050China

Background:Pulsed radiofrequency (PRF) is a minimally invasive interventional technique that provides a novel and effective treatment strategy for neuropathic pain (NP).PRF is advantageous because it does not damage nerves and avoids sensory loss after treatment.At present,animal studies have demonstrated that PRF is safe and effective for relieving the NP associated with sciatic nerve damage in rats with chronic constriction injury (CCI).However,the mechanism through which this effect occurs is unknown.An increasing body of evidence shows that the expression of the P2X ligand-gated ion channel 3 (P2X3) receptor is closely related to NP;this study was to investigate whether the expression of this receptor is involved in NP relief due to PRF.Methods:A total of 36 healthy adult male Sprague-Dawley (SD) rats were randomly divided into three groups:Sham group,CCI group,and PRF group.The right sciatic nerve was ligated in CCI group and PRF group to establish a CCI model;the right sciatic nerve was separated but not ligated in Sham group.On day 14 after the operation,PRF was administered to the ligated sciatic nerve in PRF group (42℃,45 V,2 min).A non-live electrode was placed at the exposed sciatic nerve for the rats in Sham and CCI groups.The hindpaw withdrawal threshold (HWT) and thermal withdrawal latency (TWL) were measured at the right hindpaw at different time points before and after PRF or sham therapy.On day 28 after treatment,the dorsal root ganglion (DRG) and spinal dorsal horn of the right L4-6 were harvested from each group to determine the mRNA and protein levels of the P2X3 receptor.Results:On day 28 after PRF treatment,the HWT (8.33 ± 0.67 g vs.3.62 ± 0.48 g) and TWL (25.42 ± 1.90 s vs.15.10 ± 1.71 s) were significantly higher in PRF group as compared to CCI group (P < 0.05).The mRNA expression of the P2X3 receptor in the DRG in PRF group was 23.7% lower than that in CCI group (P < 0.05),in the spinal dorsal horns in PRF group was 22.7% lower than that in CCI group (P < 0.05).The protein expression of t

关键词： Pulsed radiofrequency P2X3 receptor neuropathic pain Chronic constriction injury

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Increased CXCL13 and CXCR5 in Anterior Cingulate Cortex Contributes to neuropathic Pain-Related Conditioned Place Aversion

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Neuroscience Bulletin 2019年第4期35卷 613-623页

作者： Xiao-Bo Wu Li-Na He Bao-Chun Jiang Xue Wang Ying Lu Yong-Jing Gao Institute of Pain Medicine Institute of Special Environmental Medicine Nantong University Nantong 226019 China Department of Nutrition and Food Hygiene School of Public Health Nantong University Nantong 226019 China Co-innovation Center of Neuroregeneration Nantong University Nantong 226001 China

Pain consists of sensory-discriminative and emotional-affective components.The anterior cingulate cortex(ACC)is a critical brain area in mediating the affective pain.However,the molecular mechanisms involved remain largely unknown.Our recent study indicated that C-X-C motif chemokine 13(CXCL13)and its sole receptor CXCR5 are involved in sensory sensitization in the spinal cord after spinal nerve ligation(SNL).Whether CXCL13/CXCR5 signaling in the ACC contributes to the pathogenesis of pain-related aversion remains unknown.Here,we showed that SNL increased the CXCL13 level and CXCR5 expression in the ACC after SNL.Knockdown of CXCR5 by microinjection of Cxcr5 shRNA into the ACC did not affect SNL-induced mechanical allodynia but effectively alleviated neuropathic painrelated place avoidance behavior.Furthermore,electrophysiological recording from layer Ⅱ-Ⅲ neurons in the ACC showed that SNL increased the frequency and amplitude of spontaneous excitatory postsynaptic currents(sEPSCs),decreased the EPSC paired-pulse ratio,and increased the α-amino-3-hydroxy-5-methyl-4-isoxazolepropionic acid receptor/N-methyl-D-aspartate receptor ratio,indicating enhanced glutamatergic synaptic transmission.Finally,superfusion of CXCL13 onto ACC slices increased the frequency and amplitude of spontaneous EPSCs.Pre-injection of Cxcr5 shRNA into the ACC reduced the increase in glutamatergic synaptic transmis sion induced by SNL.Collectively,these results suggest that CXCL13/CXCR5 signaling in the ACC is involved in neuropathic pain-related aversion via synaptic potentiation.

关键词： CXCL13 CXCR5 Anterior cingulate cortex neuropathic pain Conditioned place aversion Synaptic transmission

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Muscovite nanoparticles mitigate neuropathic pain by modulating the inflammatory response and neuroglial activation in the spinal cord

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Neural Regeneration Research 2020年第11期15卷 2162-2168页

作者： Ju-Young Oh Tae-Yeon Hwang Jae-Hwan Jang Ji-Yeun Park Yeonhee Ryu HyeJung Lee Hi-Joon Park Acupuncture and Meridian Science Research Center Kyung Hee University26 Kyungheedae-roDongdaemun-guSeoulRepublic of Korea Department of Korean Medical Science Graduate School of Korean MedicineKyung Hee UniversitySeoulRepublic of Korea BK21 PLUS Korean Medicine Science Center College of Korean MedicineKyung Hee UniversitySeoulRepublic of Korea College of Korean Medicine Daejeon UniversityDaejeonRepublic of Korea Korean Institute of Oriental Medicine DaejeonRepublic of Korea

Despite numerous efforts to overcome neuropathic pain,various pharmacological drugs often fail to meet the needs and have many side effects.Muscovite is an aluminosilicate mineral that has been reported to have an anti-inflammatory effect,but the efficacy of muscovite for neuropathic pain has not been investigated.Here,we assessed whether muscovite nanoparticles can reduce the symptoms of pain by controlling the inflammatory process observed in neuropathic pain.The analgesic effects of muscovite nanoparticles were explored using partial sciatic nerve ligation model of neuropathic pain,in which one-third to onehalf of the nerve trifurcation of the sciatic nerve was tightly tied to the dorsal side.Muscovite nanoparticles(4 mg/100μL)was given intramuscularly to evaluate its effects on neuropathic pain(3 days per week for 4 weeks).The results showed that the muscovite nanoparticle injections significantly alleviated partial sciatic nerve ligation-induced mechanical and cold allodynia.In the spinal cord,the muscovite nanoparticle injections exhibited inhibitory effects on astrocyte and microglia activation and reduced the expression of pro-inflammatory cytokines,such as interleukin-1β,tumor necrosis factor-α,interleiukin-6 and monocyte chemoattractant protein-1,which were upregulated in the partial sciatic nerve ligation model.Moreover,the muscovite nanoparticle injections resulted in a decrease in activating transcription factor 3,a neuronal injury marker,in the sciatic nerve.These results suggest that the analgesic effects of muscovite nanoparticle on partial sciatic nerve ligation-induced neuropathic pain may result from inhibiting activation of astrocytes and microglia as well as pro-inflammatory cytokines.We propose that muscovite nanoparticle is a potential anti-nociceptive candidate for neuropathic pain.All experimental protocols in this study were approved by the Institutional Animal Ethics Committee(IACUC)at Dongguk University,South Korea(approval No.2017-022-1)on September 28,2017.

关键词： astrocyte microglia muscovite nanoparticle neuropathic pain partial sciatic nerve ligation pharmacopuncture pro-inflammatory cytokine spinal cord

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Mechanism of persistent hyperalgesia in neuropathic pain caused by chronic constriction injury

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Neural Regeneration Research 2019年第6期14卷 1091-1098页

作者： Qin-Yi Chen Chao-Yang Tan Yang Wang Ke-Tao Ma Li Li Jun-Qiang Si Department of Anesthesiology First Affiliated Hospital of Shihezi UniversityShihezi Department of Physiology Medical College of Shihezi UniversityShihezi Key Laboratory of Xinjiang Endemic and Ethnic Disease Shihezi University School of MedicineShihezi Department of Neurobiology Tongji Medical CollegeHuazhong University of Science and Technology

Transmembrane member 16 A(TMEM16 A) is involved in many physiological functions, such as epithelial secretion, sensory conduction, nociception, control of neuronal excitability, and regulation of smooth muscle contraction, and may be important in peripheral pain transmission. To explore the role of TMEM16 A in the persistent hyperalgesia that results from chronic constriction injury-induced neuropathic pain, a rat model of the condition was established by ligating the left sciatic nerve. A TMEM16 A selective antagonist(10 μg T16 Ainh-A01) was intrathecally injected at L5–6. For measurement of thermal hyperalgesia, the drug was administered once at 14 days and thermal withdrawal latency was recorded with an analgesia meter. For measurement of other indexes, the drug was administered at 12 days,once every 6 hours, totally five times. The measurements were performed at 14 days. Western blot assay was conducted to analyze TMEM16 A expression in the L4–6 dorsal root ganglion. Immunofluorescence staining was used to detect the immunoreactivity of TMEM16 A in the L4–6 dorsal root ganglion on the injured side. Patch clamp was used to detect electrophysiological changes in the neurons in the L4–6 dorsal root ganglion. Our results demonstrated that thermal withdrawal latency was shortened in the model rats compared with control rats.Additionally, TMEM16 A expression and the number of TMEM16 A positive cells in the L4–6 dorsal root ganglion were higher in the model rats, which induced excitation of the neurons in the L4–6 dorsal root ganglion. These findings were inhibited by T16 Ainh-A01 and confirm that TMEM16 A plays a key role in persistent chronic constriction injury-induced hyperalgesia. Thus, inhibiting TMEM16 A might be a novel pharmacological intervention for neuropathic pain. All experimental protocols were approved by the Animal Ethics Committee at the First Affiliated Hospital of Shihezi University School of Medicine, China(approval No. A2017-170-01) on February 27, 2017.

关键词： nerve regeneration TMEM16A calcium-activated chloride channels T16Ainh-A01 neuropathic pain dorsal root ganglia hyperalgesia action potential rheobase chronic constriction injury peripheral nerve injury neural regeneration

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Inhibitory Effect of Anisodamine on the neuropathic Hyperalgesia Following Peripheral Nerve Injury(Ⅱ)

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Science China Chemistry 1993年第7期36卷 824-834页

作者：谢益宽肖文华 Institute of Basic Medical Sciences Chinese Academy of Medical Sciences Beijing 100005 PRC

A peripheral neuropathy with hyperalgesia and allodynia was produced by loosely tying constrictive ligature around the left sciatic nerve of rats, i.v. injection of anisodamine 20mg/Kg abolished both neuropathic hyperalgesia responses to noxious radiant heat and ectopic discharges generated from the injured region of the nerve. Anisodanime applied either systemically or locally to the damaged area of the nerve not only ceased the spontaneous ectopic discharges recorded from Aβ to C fibers but also blocked the afferent ectopic discharge elicited by K+ channel blocker, noradrenaline, Ca2+ or antidromic stimulation of sciatic nerve proximal to the injured nerve area. The experiments indicated that anisodamine probably possessed a calcium channel blocker-like activity and produced selective block of the new channels in the injured area. It is suggested that anisodamine may be a candidate therapeutic agent in relieving hyperalgesia and allodynia following nerve injury.

关键词： nerve injury hyperalgesia neuropathic pain ectopic discharge anisodamine.

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MicroRNA21 Meets Neuronal TLR8: Non-canonical Functions of MicroRNA in neuropathic Pain

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Neuroscience Bulletin 2019年第5期35卷 949-952页

作者： Zhi-Hong Wang Tong Liu Jiangsu Key Laboratory of Neuropsychiatric Diseases and Institute of Neuroscience Soochow University Suzhou 215021 China College of Life Sciences Yanan University Yanan 716000 China

Toll-like receptors (TLRs) are well-known as patternrecognition receptors in the immune system for recognizing pathogen-associated and damage-associated molecular patterns [1]. TLRs play an essential role in the innate and adaptive immune responses. To date, 10 functional TLRs have been identified in humans (TLR1–TLR10) and 12 in mice (TLR1–TLR9 and TLR11–TLR13)[1]. TLRs are evolutionarily conserved type I transmembrane proteins and comprise an ectodomain characterized by leucine-rich repeats mediating the recognition of ligands, a transmembrane region, and cytosolic Toll-interleukin (IL)-1 receptor domains that activate the downstream signaling pathways [1].

关键词： MicroRNA21 Neuronal TLR8 neuropathic Pain

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Unilateral peripheral neuropathic pain: The role of neurodiagnostic skin biopsy

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World Journal of Clinical Cases 2014年第2期2卷 27-31页

作者： Michelangelo Buonocore Unit of Clinical Neurophysiology and Neurodiagnostic Skin Biopsy Fondazione Salvatore Maugeri Scientific Institute of Pavia27100 Pavia Italy

According to the current definition of neuropathic pain("pain arising as a direct consequence of a lesion or disease affecting the somatosensory system"), the demonstration of a lesion or disease involving the somatosensory system is mandatory for the diagnosis of definite neuropathic pain. Although several methods are currently available for this aim, none is suitable for every type of disease(or lesion). Neurodiagnostic skin biopsy(NSB) is a relatively new technique for the diagnosis of peripheral nerve lesions. It is an objective method, completely independent from the patient's complaining, based on immunohistochemical staining techniques that allow measurement of the density of the epidermal nerve fibers, currently considered the free nerve endings of small diameter(A-delta and C) afferent fibers. NSB has the important property of being used to investigate the skin, allowing obtaining a diagnosis of small fiber axonal neuropathy of peripheral nerves supplying every body part covered by skin. This feature appears to be very important, particularly in cases of unilateral nerve lesions, because it allows going beyond the possibilities of neurophysiological tests which are available only for a limited number of peripheral nerves. All these characteristics make NSB a precious instrument for the diagnosis of peripheral unilateral neuropathic pain.

关键词： Skin biopsy neuropathic pain Diagnosis Peripheral nerve lesion Innervation

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Emerging roles of GPR109A in regulation of neuroinflammation in neurological diseases and pain

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Neural Regeneration Research 2023年第4期18卷 763-768页

作者： Kyle Taing Lawrence Chen Han-Rong Weng Department of Basic Sciences California Northstate University College of MedicineElk GroveCAUSA

Neuroinflammation plays a critical role in the pathological process of multiple neurological disorders and pathological pain conditions.GPR109A,a Gi protein-coupled receptor,has emerged as an important therapeutic target for controlling inflammation in various tissues and organs.In this review,we summarized current data about the role of GPR109A in neuroinflammation.Specifically,we focused on the pharmacological features of GPR109A and signaling pathways used by GPR109A to ameliorate neuroinflammation and symptoms in Alzheimer’s disease,Parkinson’s disease,multiple sclerosis,stroke,and pathological pain conditions.

关键词： β-hydroxybutyrate cytokines HCAR2 lupus neuroinflammation neuropathic niacin nociception synaptic

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neuropathic arthropathy of the shoulder: Two cases of syringomyelia with cocaine use

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Open Journal of Internal Medicine 2012年第1期2卷 27-30页

作者： Jerry A. Rubano Suleman Bhana Dodji Modjinou Colette R. J. Pameijer Heidi Roppelt Divisions of Surgical Oncology/Upper Gastrointestinal Surgery and Rheumatology Stony Brook University Hospital New York USA

neuropathic arthropathy (NA) is a progressive, degenerative disorder associated with decreased sensory innervation of the involved joints. The shoulder joint is an uncommon presentation for NA, although syringomyelia is the most common cause for this joint. Two cases are presented of NA of the shoulder, with both patients having a history of syringomyelia and cocaine use. In both cases a work up for malignancy was negative, but imaging was consistent with NA. Although syringomyelia has been linked with this presentation in prior publications, the role of cocaine use may not be incidental, with complex biochemical interactions in bone metabolism. Cocaine has been shown to involve the Leptin, Neuromedin U (NmU), cocaine and amphetamine-regulated transcript (CART), and Receptor activator of nuclear factor kappa-B ligand (RANKL) pathways of bone remodeling. Treatment can be challenging, involving concurrent use of pharmacotherapy, surgical correction, and protective bracing.

关键词： neuropathic Arthropathy Charcot Syringomyelia Cocaine RANKL

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