RESUMEN
AIMS: Chronic pain is highly associated with anxiety. Electroacupuncture (EA) is effective in relieving pain and anxiety. Currently, little is known about the neural mechanisms underlying the comorbidity of chronic pain and anxiety and the EA mechanism. This study investigated a potential neural circuit underlying the comorbid and EA mechanisms. METHODS: Spared nerve injury (SNI) surgery established the chronic neuropathic pain mouse model. The neural circuit was activated or inhibited using the chemogenetic method to explore the relationship between the neural circuit and mechanical allodynia and anxiety-like behaviors. EA combined with the chemogenetic method was used to explore whether the effects of EA were related to this neural circuit. RESULTS: EA attenuated mechanical allodynia and anxiety-like behaviors in SNI mice, which may be associated with the activity of CaMKII neurons in the basolateral amygdala (BLA). Inhibition of BLACaMKII-rACC induced mechanical allodynia and anxiety-like behaviors in sham mice. Activation of the BLACaMKII-rACC alleviated neuropathic pain and anxiety-like behaviors in SNI mice. The analgesic and anxiolytic effects of 2 Hz EA were antagonized by the inhibition of the BLACaMKII-rACC. CONCLUSION: BLACaMKII-rACC mediates mechanical allodynia and anxiety-like behaviors. The analgesic and anxiolytic effects of 2 Hz EA may be associated with the BLACaMKII-rACC.
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Ansiedad , Complejo Nuclear Basolateral , Electroacupuntura , Giro del Cíngulo , Hiperalgesia , Animales , Electroacupuntura/métodos , Hiperalgesia/terapia , Ansiedad/terapia , Ansiedad/psicología , Masculino , Ratones , Complejo Nuclear Basolateral/metabolismo , Ratones Endogámicos C57BL , Neuralgia/terapia , Neuralgia/psicología , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Vías NerviosasRESUMEN
BACKGROUND: Individuals with spinal cord injury (SCI) often suffer from neuropathic pain which is often disabling and negatively affects function, participation, and quality of life (QoL). Pharmacological treatments lack efficacy in neuropathic pain reduction hence studying alternatives to drug treatment is necessary. Preclinical evidence of various aerobic exercises has shown positive effects on neuropathic pain but scientific studies investigating its effect in the SCI human population are limited. METHODOLOGY: This study is a double-blind, parallel, two-group, randomized controlled trial with an interventional study design that aims to evaluate the effectiveness of aerobic exercise program on neuropathic pain and quality of life (QoL) in individuals with chronic paraplegia. Thirty individuals with chronic paraplegia with the neurological level of injury from T2 to L2 will be recruited from the rehabilitation department at a super specialty hospital based on the inclusion criteria. Using a 1:1 allocation ratio, the participants will be randomly assigned to one of the two groups. The intervention group will perform high-intensity interval training (HIIT) aerobic exercise using an arm ergometer based on their peak heart rate, and the control group will perform free-hand arm aerobic exercise. In both groups, the intervention will be delivered as 30-min sessions, four times a week for 6 weeks. OUTCOME MEASURES: International Spinal Cord Injury Pain Basic Data Set Version 3.0 will be used for diagnosing and assessing neuropathic pain and its interference with day-to-day activities, mood, and sleep. The International Spinal Cord Society (ISCoS) QoL basic data set will be used to assess QoL, and 6-min push test distance will be used to assess peak heart rate and aerobic capacity. DISCUSSION: The effectiveness of the aerobic exercise program will be assessed based on the changes in neuropathic pain score and its interference with day-to-day activities, mood, sleep, QoL, and aerobic capacity after 3 weeks mid-intervention and after 6 weeks post-intervention. The trial will provide new knowledge about the effectiveness of the aerobic exercise program in improving neuropathic pain and QoL in individuals with chronic paraplegia. TRIAL REGISTRATION: Clinical Trials Registry-India CTRI/2023/08/056257. Registered on 8 August 2023.
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Terapia por Ejercicio , Neuralgia , Paraplejía , Calidad de Vida , Ensayos Clínicos Controlados Aleatorios como Asunto , Traumatismos de la Médula Espinal , Humanos , Neuralgia/terapia , Neuralgia/fisiopatología , Neuralgia/psicología , Paraplejía/rehabilitación , Paraplejía/fisiopatología , Paraplejía/psicología , Método Doble Ciego , Terapia por Ejercicio/métodos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/fisiopatología , Traumatismos de la Médula Espinal/psicología , Adulto , Persona de Mediana Edad , Resultado del Tratamiento , Masculino , Femenino , Ejercicio Físico , Dimensión del Dolor , Factores de Tiempo , Adulto JovenRESUMEN
OBJECTIVE: To observe the clinical effect of guasha-fangsha (scrapping and bleeding) therapy combined with electroacupuncture (EA) on greater occipital neuralgia. METHODS: Ninety patients with greater occipital neuralgia were randomly divided into an observation group (45 cases) and a control group (45 cases, 2 cases dropped out). In the control group, EA was delivered at Fengfu (GV 16) and bilateral Tianzhu (BL 10), Fengchi (GB 20), Wangu (GB 12), Yuzhen (BL 9) and Houxi (SI 3), with disperse-dense wave, at 2 Hz/100 Hz in frequency and 2 mA to 6 mA in intensity, for 30 min in each intervention, once every other days, 3 times a week. In the observation group, on the basis of the intervention as the control group, guasha-fangsha therapy was used along the distribution of the bladder meridian of foot-taiyang on the occipital region and that of the gallbladder meridian of foot-shaoyang on the lateral side of the head, once weekly. The duration of treatment was 3 weeks in the two groups. In the two groups, before treatment, after 1, 2 and 3 weeks of treatment and in follow-up visit after 3 weeks of treatment completion, the score of visual analogue scale (VAS) was observed; before and after treatment, as well as in follow-up visit after 3 weeks of treatment completion, the scores of self-rating anxiety scale (SAS), self-rating depression scale (SDS) and 36-item short-form health survey (SF-36) were observed; after treatment and in follow-up visit after 3 weeks of treatment completion, the clinical efficacy was evaluated. RESULTS: After one week of treatment, the VAS score in the observation group decreased when compared with that before treatment (P<0.05), while the scores in 2 and 3 weeks of treatment and in follow-up visit after 3 weeks of treatment completion were lower than those before treatment in the two groups (P<0.05) separately. At each time point after treatment, the VAS scores in the observation group were lower than those in the control group (P<0.05). After treatment and during the follow-up visit, the scores of SAS and SDS decreased when compared with those before treatment in the two groups (P<0.05), and the scores in the observation group were lower than those in the control group (P<0.05); the scores of each item in SF-36 were elevated in comparison with those before treatment in the two groups (P<0.05), and the scores in the observation group were higher than those in the control group (P<0.05). After treatment, the total effective rate of the observation group was 91.1% (41/45), higher than that (76.7%, 33/43) of the control group (P<0.05). In follow-up visit, the total effective rate of the observation group was 91.1% (41/45), which was higher than 72.1% (31/43) of the control group (P<0.05). CONCLUSION: Guasha-fangsha therapy combined with electroacupuncture can effectively relieve greater occipital neuralgia, alleviate pain severity, ameliorate anxiety and depression and improve the quality of life in the patients.
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Electroacupuntura , Neuralgia , Humanos , Masculino , Femenino , Persona de Mediana Edad , Neuralgia/terapia , Adulto , Anciano , Resultado del Tratamiento , Terapia Combinada , Puntos de Acupuntura , Terapia por Acupuntura , Adulto JovenRESUMEN
BACKGROUND: Our previous study synthesized the analgesic effects of repetitive Transcranial Magnetic Stimulation (rTMS) over the dorsolateral prefrontal cortex (DLPFC) trials up to 2019. There has been a significant increase in pain trials in the past few years, along with methodological variabilities such as sample size, stimulation intensity, and rTMS paradigms. OBJECTIVES/METHODS: This study therefore updated the effects of DLPFC-rTMS on chronic pain and quantified the impact of methodological differences across studies. RESULTS: A total of 36 studies were included. Among them, 26 studies were clinical trials (update = 9, 307/711 patients), and 10 (update = 1, 34/249 participants) were provoked pain studies. The updated meta-analysis does not support an effect on neuropathic pain after including the additional trials (pshort-term = 0.20, pmid-term = 0.50). However, there is medium-to-large analgesic effect in migraine trials extending up to six weeks follow-up (SMDmid-term = -0.80, SMDlong-term = -0.51), that was not previously reported. Methodological differences wthine the studies were considered. DLPFC-rTMS also induces potential improvement in the emotional aspects of pain (SMDshort-term = -0.28). CONCLUSIONS: The updated systematic meta-analysis continues to support analgesic effects for chronic pain overall. However, the updated results no longer support DLPFC-rTMS for pain relief in neuropathic pain, and do supports DLPFC-rTMS in the management of migraine. There is also evidence for DLPFC-rTMS to improve emotional aspects of pain.
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Corteza Prefontal Dorsolateral , Estimulación Magnética Transcraneal , Humanos , Estimulación Magnética Transcraneal/métodos , Corteza Prefontal Dorsolateral/fisiología , Manejo del Dolor/métodos , Dolor Crónico/terapia , Neuralgia/terapia , Corteza Prefrontal/fisiología , Corteza Prefrontal/fisiopatologíaRESUMEN
STUDY DESIGN: A feasibility pilot study. OBJECTIVE: To assess the feasibility a full-scale Randomized Controlled Trial aimed at assessing the beneficial effect of a Virtual Walking (VW)-based (Experimental intervention (EI)) on neuropathic pain and functionality in people with incomplete spinal cord injury (SCI). SETTING: A hospital service (Hospital Universitario y Politécnico La Fe) and disability associations (TetraSport, CODIFIVA and ASPAYM). METHODS: Twelve people with chronic incomplete SCI were randomized to EI (VW plus therapeutic exercise program (TE)) -or Control Intervention (CI (placebo VW and TE)) groups. A six-week intervention (3 sessions/week) was carried out. To assess feasibility, the following outcomes were used: level of restriction and validity of inclusion and exclusion criteria, participants' compliance, accessibility and acceptability of the intervention for participants, adequate pre-training time of physiotherapists. To explore therapy effectiveness, pain severity, and interference, mean and maximum isometric strength, walking speed, and walking ability were assessed before (Time 1, T1) and after (Time 2, T2) the intervention. RESULTS: 20% of the participants initially recruited did not meet inclusion criteria. In addition, all participants completed at least 80% of the intervention sessions and none of the participants dropped out before T2. No serious adverse event was found. Moreover, 91.67% of participants were willing to perform the intervention again and all therapists involved were adequately pre-trained. Finally, our preliminary results suggest that the proposed EI is effective. CONCLUSION: A full-scale RCT is feasible and preliminary results suggest that VW with TE could have a beneficial impact on pain and functionality in this population.
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Terapia por Ejercicio , Estudios de Factibilidad , Traumatismos de la Médula Espinal , Caminata , Humanos , Traumatismos de la Médula Espinal/complicaciones , Traumatismos de la Médula Espinal/rehabilitación , Traumatismos de la Médula Espinal/terapia , Masculino , Femenino , Persona de Mediana Edad , Terapia por Ejercicio/métodos , Adulto , Caminata/fisiología , Proyectos Piloto , Resultado del Tratamiento , Neuralgia/terapia , Neuralgia/etiología , AncianoRESUMEN
Spinal cord injury (SCI) is a serious and disabling injury that is often accompanied by neuropathic pain (NeP), which severely affects patients' motor and sensory functions and reduces their quality of life. Currently, there is no specific treatment for treating SCI and relieving the accompanying pain, and we can only rely on medication and physical rehabilitation, both of which are ineffective. Researchers have recently identified a novel class of glial cells, olfactory ensheathing cells (OECs), which originate from the olfactory system. Transplantation of OECs into damaged spinal cords has demonstrated their capacity to repair damaged nerves, improve the microenvironment at the point of injury, and They can also restore neural connectivity and alleviate the patient's NeP to a certain extent. Although the effectiveness of OECs transplantation has been confirmed in experiments, the specific mechanisms by which it repairs the spinal cord and relieves pain have not been articulated. Through a review of the literature, it has been established that the ability of OECs to repair and relieve pain is inextricably linked to its anti-inflammatory and immunomodulatory effects. In this regard, it is imperative to gain a deeper understanding of how OECs exert their anti-inflammatory and immunomodulatory effects. The objective of this paper is to provide a comprehensive overview of the mechanisms by which OECs exert anti-inflammatory and immunomodulatory effects. We aim to manipulate the immune microenvironment at the transplantation site through the intervention of cytokines and immune cells, with the goal of enhancing OECs' function or creating a conducive microenvironment for OECs' survival. This approach is expected to improve the therapeutic efficacy of OECs in clinical settings. However, numerous fundamental and clinical challenges remain to be addressed if OEC transplantation therapy is to become a standardized treatment in clinical practice.
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Traumatismos de la Médula Espinal , Traumatismos de la Médula Espinal/terapia , Traumatismos de la Médula Espinal/complicaciones , Humanos , Animales , Neuralgia/terapia , Antiinflamatorios/uso terapéutico , Antiinflamatorios/farmacología , Trasplante de Células/métodos , Bulbo Olfatorio/citología , Neuroglía/trasplanteRESUMEN
Pathological nociception arising from peripheral nerve injury impacts quality of life. Current therapeutics are generally ineffective. However, photobiomodulation therapy (PBMT) has shown promise in addressing this issue. We aimed to assess the potential anti-allodynic effects of 2 p.m. protocols, each applied transcutaneously over the peripheral nerve injury. In addition to evaluating nociceptive behavior, we also conducted morphological analysis using electron microscopy (EM) to investigate potential ultrastructural changes at the cellular level. We sought to determine, using the chronic constriction injury (CCI) model, whether our parameters could alleviate established allodynia and/or dampen allodynia development. Adult male and female rats with CCI or sham were treated with PBMT (850-nm wavelength) for 2 min, 3 times a week over three or four weeks across three studies, where PBMT began either before or after CCI. Allodynia was assessed prior to surgery and across weeks and, at the conclusion of the third study, sciatic nerve was processed for EM and histomorphometrically evaluated. The results showed that PBMT before versus after CCI injury yielded similar behaviors, effectively decreasing allodynia. Interestingly, these positive effects of PBMT do not appear to be accounted by protection of the sciatic injury site, based on EM. CCI reliably decreased axon size and the number of myelinated axons present in both PBMT and control groups. While PBMT reduced the number of C-fibers in CCI samples, no improvement in any measure was observed in response to PBMT.
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Hiperalgesia , Terapia por Luz de Baja Intensidad , Neuralgia , Ratas Sprague-Dawley , Animales , Femenino , Terapia por Luz de Baja Intensidad/métodos , Masculino , Neuralgia/terapia , Neuralgia/radioterapia , Neuralgia/etiología , Hiperalgesia/terapia , Ratas , Modelos Animales de Enfermedad , Nervio Ciático/efectos de la radiación , Nervio Ciático/lesiones , Dimensión del Dolor , Rayos Infrarrojos/uso terapéuticoRESUMEN
As the Coronavirus Disease 2019 (COVID-19) pandemic continues, there is a growing concern regarding the relationship between viral infections and neuropathic pain. Chronic neuropathic pain resulting from virus-induced neural dysfunction has emerged as a significant issue currently faced. However, the molecular mechanisms underlying this phenomenon remain unclear, and clinical treatment outcomes are often suboptimal. Therefore, delving into the relationship between viral infections and neuropathic pain, exploring the pathophysiological characteristics and molecular mechanisms of different viral pain models, can contribute to the discovery of potential therapeutic targets and methods, thereby enhancing pain relief and improving the quality of life for patients. This review focuses on HIV-related neuropathic pain (HNP), postherpetic neuralgia (PHN), and neuropathic pain caused by Severe Acute Respiratory Syndrome Coronavirus 2 (SARS-CoV-2) infections, examining rodent models and relevant cellular molecular pathways. Through elucidating the connection between viral infections and neuropathic pain, it aims to delineate the current limitations and challenges faced by treatments, thereby providing insights and directions for future clinical practice and research.
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COVID-19 , Neuralgia , SARS-CoV-2 , Humanos , Neuralgia/virología , Neuralgia/terapia , Neuralgia/etiología , Animales , COVID-19/complicaciones , COVID-19/virología , COVID-19/terapia , Infecciones por VIH/complicaciones , Infecciones por VIH/virología , Infecciones por VIH/tratamiento farmacológico , Neuralgia Posherpética/virología , Neuralgia Posherpética/terapiaRESUMEN
Implantable devices interfacing with peripheral nerves exhibit limited longevity and resolution. Poor nerve-electrode interface quality, invasive surgical placement and development of foreign body reaction combine to limit research and clinical application of these devices. Here, we develop cuff implants with a conformable design that achieve high-quality and stable interfacing with nerves in chronic implantation scenarios. When implanted in sensorimotor nerves of the arm in awake rats for 21 days, the devices record nerve action potentials with fascicle-specific resolution and extract from these the conduction velocity and direction of propagation. The cuffs exhibit high biocompatibility, producing lower levels of fibrotic scarring than clinically equivalent PDMS silicone cuffs. In addition to recording nerve activity, the devices are able to modulate nerve activity at sub-nerve resolution to produce a wide range of paw movements. When used in a partial nerve ligation rodent model, the cuffs identify and characterise changes in nerve C fibre activity associated with the development of neuropathic pain in freely-moving animals. The developed implantable devices represent a platform enabling new forms of fine nerve signal sensing and modulation, with applications in physiology research and closed-loop therapeutics.
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Potenciales de Acción , Nervios Periféricos , Animales , Nervios Periféricos/fisiología , Ratas , Potenciales de Acción/fisiología , Masculino , Electrodos Implantados , Neuralgia/fisiopatología , Neuralgia/terapia , Ratas Sprague-Dawley , Prótesis e Implantes , Conducción Nerviosa/fisiologíaRESUMEN
Both of exosomes derived from mesenchymal stem cells (MSCs) and glial cell line-derived neurotrophic factor (GDNF) show potential for the treatment of neuropathic pain. Here, the analgesic effects of exosomes derived from bone marrow MSCs (BMSCs) were investigated. BMSCs-derived exosomes were isolated and characterized. Chronic constriction injury (CCI) was constructed to induce neuropathic pain in rats, which were then treated with exosomes. Pain behaviors were evaluated by measuring paw withdrawal thresholds and latency. The changes of key proteins, including cytokines, were explored using Western blot and ELISA. Administration of BMSCs-derived exosomes alleviated neuropathic pain, as demonstrated by the decrease of thermal hyperalgesia and mechanical allodynia, as well as the reduced secretion of pro-inflammatory cytokines in CCI rats. These effects were comparable to the treatment of GDNF alone. Mechanically, the exosomes suppressed the CCI-induced activation of TLR2/MyD88/NF-κB signaling pathway, while GDNF knockdown impaired their analgesic effects on CCI rat. BMSCs-derived exosomes may alleviate CCI-induced neuropathic pain and inflammation in rats by transporting GDNF.
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Modelos Animales de Enfermedad , Exosomas , Factor Neurotrófico Derivado de la Línea Celular Glial , Hiperalgesia , Células Madre Mesenquimatosas , Factor 88 de Diferenciación Mieloide , FN-kappa B , Ratas Sprague-Dawley , Transducción de Señal , Receptor Toll-Like 2 , Animales , Exosomas/trasplante , Ratas , Factor Neurotrófico Derivado de la Línea Celular Glial/genética , Masculino , Hiperalgesia/etiología , Factor 88 de Diferenciación Mieloide/genética , FN-kappa B/metabolismo , Receptor Toll-Like 2/genética , Receptor Toll-Like 2/biosíntesis , Neuralgia/etiología , Neuralgia/terapia , Citocinas , Trasplante de Células Madre Mesenquimatosas , Células de la Médula Ósea , Neuropatía Ciática , ConstricciónRESUMEN
OBJECTIVE: Rehabilitation interventions for chronic pain typically include education, cognitive behavioural therapy, and exercise therapy, or a combination of these. A systematic review and meta-analysis of rehabilitation interventions for neuropathic pain was conducted. DESIGN: Randomized controlled trials were identified in PubMed, EMBASE, Cochrane Central Register of Controlled Trials, and PsycINFO databases from inception up to 3 March 2022. SUBJECTS/PATIENTS: Adults with chronic (> 3 months) neuropathic pain. METHODS: Primary outcomes were pain intensity, pain-related disability, and work participation. Secondary outcomes were quality of life, emotional strain, insomnia, and adverse outcomes, according to VAPAIN guidelines. Analyses were made post-intervention, which was defined as the assessment point immediately following the intervention or at the first-time measurement conducted after the intervention period. RESULTS: In total, 15 studies (total population, n = 764) were incorporated. Most common interventions were cognitive behavioural programmes including acceptance and commitment therapy (n = 4), mindfulness-based interventions (n = 5), and yoga (n = 2). Psychological interventions reduced both pain intensity (SMD -0.49, 95% CI -0.88 to -0.10) and pain-related disability (SMD -0.51, 95% CI -0.98 to -0.03), whereas other interventions had an effect on pain intensity but not on pain-related disability. CONCLUSION: Rehabilitation interventions, and psychological interventions in particular, seem to be of value for patients with chronic neuropathic pain.
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Terapia Cognitivo-Conductual , Neuralgia , Ensayos Clínicos Controlados Aleatorios como Asunto , Humanos , Neuralgia/rehabilitación , Neuralgia/terapia , Terapia Cognitivo-Conductual/métodos , Terapia por Ejercicio/métodos , Calidad de Vida , Dolor Crónico/rehabilitación , Dolor Crónico/terapia , Dimensión del Dolor , Atención Plena/métodos , Yoga , Terapia de Aceptación y Compromiso/métodosRESUMEN
BACKGROUND: Central neuropathic pain after foramen magnum decompression (FMD) for Chiari malformation type 1 (CM-1) with syringomyelia can be residual and refractory. Here we present a case of refractory central neuropathic pain after FMD in a CM-1 patient with syringomyelia who achieved improvements in pain following spinal cord stimulation (SCS) using fast-acting sub-perception therapy (FAST™). CASE PRESENTATION: A 76-year-old woman presented with a history of several years of bilateral upper extremity and chest-back pain. CM-1 and syringomyelia were diagnosed. The pain proved drug resistant, so FMD was performed for pain relief. After FMD, magnetic resonance imaging showed shrinkage of the syrinx. Pain was relieved, but bilateral finger, upper arm and thoracic back pain flared-up 10 months later. Due to pharmacotherapy resistance, SCS was planned for the purpose of improving pain. A percutaneous trial of SCS showed no improvement of pain with conventional SCS alone or in combination with Contour™, but the combination of FAST™ and Contour™ did improve pain. Three years after FMD, percutaneous leads and an implantable pulse generator were implanted. The program was set to FAST™ and Contour™. After implantation, pain as assessed using the McGill Pain Questionnaire and visual analog scale was relieved even after reducing dosages of analgesic. No adverse events were encountered. CONCLUSION: Percutaneously implanted SCS using FAST™ may be effective for refractory pain after FMD for CM-1 with syringomyelia.
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Malformación de Arnold-Chiari , Neuralgia , Estimulación de la Médula Espinal , Siringomielia , Humanos , Siringomielia/complicaciones , Femenino , Malformación de Arnold-Chiari/complicaciones , Malformación de Arnold-Chiari/cirugía , Anciano , Neuralgia/etiología , Neuralgia/terapia , Estimulación de la Médula Espinal/métodos , Dolor Postoperatorio/terapia , Dolor Postoperatorio/etiología , Resultado del TratamientoRESUMEN
BACKGROUND: Satellite glial cells (SGCs) in the dorsal root ganglia (DRG) play a pivotal role in the formation of neuropathic pain (NP). Sciatic nerve stimulation (SNS) neuromodulation was reported to alleviate NP and reduce neuroinflammation. However, the mechanisms underlying SNS in the DRG remain unclear. This study aimed to elucidate the mechanism of electric stimulation in reducing NP, focusing on the DRG. METHODS: L5 nerve root ligation (NRL) NP rat model was studied. Ipsilateral SNS performed 1 day after NRL. Behavioral tests were performed to assess pain phenotypes. NanoString Ncounter technology was used to explore the differentially expressed genes and cellular pathways. Activated SGCs were characterized in vivo and in vitro. The histochemical alterations of SGCs, macrophages, and neurons in DRG were examined in vivo on post-injury day 8. RESULTS: NRL induced NP behaviors including decreased pain threshold and latency on von Frey and Hargreaves tests. We found that following nerve injury, SGCs were hyperactivated, neurotoxic and had increased expression of NP-related ion channels including TRPA1, Cx43, and SGC-neuron gap junctions. Mechanistically, nerve injury induced reciprocal activation of SGCs and M1 macrophages via cytokines including IL-6, CCL3, and TNF-α mediated by the HIF-1α-NF-κB pathways. SNS suppressed SGC hyperactivation, reduced the expression of NP-related ion channels, and induced M2 macrophage polarization, thereby alleviating NP and associated neuroinflammation in the DRG. CONCLUSIONS: NRL induced hyperactivation of SGCs, which had increased expression of NP-related ion channels. Reciprocal activation of SGCs and M1 macrophages surrounding the primary sensory neurons was mediated by the HIF-1α and NF-κB pathways. SNS suppressed SGC hyperactivation and skewed M1 macrophage towards M2. Our findings establish SGC activation as a crucial pathomechanism in the gliopathic alterations in NP, which can be modulated by SNS neuromodulation.
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Modelos Animales de Enfermedad , Ganglios Espinales , Neuralgia , Enfermedades Neuroinflamatorias , Ratas Sprague-Dawley , Nervio Ciático , Animales , Ganglios Espinales/metabolismo , Neuralgia/terapia , Neuralgia/metabolismo , Masculino , Enfermedades Neuroinflamatorias/metabolismo , Nervio Ciático/patología , Macrófagos/metabolismo , Neuroglía/metabolismo , Ratas , Conducta AnimalRESUMEN
Comorbid chronic neuropathic pain and anxiety is a common disease that represents a major clinical challenge. The underlying mechanisms of chronic neuropathic pain and anxiety are not entirely understood, which limits the exploration of effective treatment methods. Glutamatergic neurons in the ventrolateral periaqueductal gray (vlPAG) have been implicated in regulating pain, but the potential roles of the vlPAG in neuropathic pain-induced anxiety have not been investigated. Herein, whole-cell recording and immunofluorescence showed that the excitability of CamkIIα neurons in the vlPAG (vlPAGCamkIIα+ neurons) was decreased in mice with spared nerve injury (SNI), while electroacupuncture (EA) activated these neurons. We also showed that chemogenetic inhibition of vlPAGCamkIIα+ neurons resulted in allodynia and anxiety-like behaviors in naive mice. Furthermore, chemogenetic activation of vlPAGCamkIIα+ neurons reduced anxiety-like behaviors and allodynia in mice with SNI, and EA had a similar effect in alleviating these symptoms. Nevertheless, EA combined with chemogenetic activation failed to further relieve allodynia and anxiety-like behaviors. Artificial inhibition of vlPAGCamkIIα+ neurons abolished the analgesic and anxiolytic effects of EA. Overall, our study reveals a novel mechanism of neuropathic pain-induced anxiety and shows that EA may relieve comorbid chronic neuropathic pain and anxiety by activating vlPAGCamkIIα+ neurons.
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Ansiedad , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina , Electroacupuntura , Neuralgia , Neuronas , Sustancia Gris Periacueductal , Animales , Neuralgia/terapia , Electroacupuntura/métodos , Neuronas/fisiología , Neuronas/metabolismo , Masculino , Ansiedad/terapia , Proteína Quinasa Tipo 2 Dependiente de Calcio Calmodulina/metabolismo , Ratones , Ratones Endogámicos C57BL , Hiperalgesia/terapia , Dolor Crónico/terapia , Ácido Glutámico/metabolismo , Modelos Animales de Enfermedad , Conducta Animal/fisiologíaRESUMEN
Fu's subcutaneous needling (FSN) is a traditional Chinese acupuncture procedure used to treat pain-related neurological disorders. Moreover, the regulation of inflammatory cytokines may provide a favorable environment for peripheral nerve regeneration. In light of this, FSN may be an important novel therapeutic strategy to alleviate pain associated with peripheral neuropathy; however, the underlying molecular mechanisms remain unclear. This study revealed that patients who had osteoarthritis with peripheral neuropathic pain significantly recovered after 1 to 2 weeks of FSN treatment according to the visual analog scale, Western Ontario and McMaster Universities Osteoarthritis Index, Lequesne index, walking speed, and passive range of motion. Similarly, we demonstrated that FSN treatment in an animal model of chronic constriction injury (CCI) significantly improved sciatic nerve pain using paw withdrawal thresholds, sciatic functional index scores, and compound muscle action potential amplitude tests. In addition, transmission electron microscopy images of sciatic nerve tissue showed that FSN effectively reduced axonal swelling, abnormal myelin sheaths, and the number of organelle vacuoles in CCI-induced animals. Mechanistically, RNA sequencing and gene set enrichment analysis revealed significantly reduced inflammatory pathways, neurotransmitters, and endoplasmic reticulum stress pathways and increased nerve regeneration factors in the FSN+CCI group, compared with that in the CCI group. Finally, immunohistochemistry, immunoblotting and enzyme-linked immunosorbent assay showed similar results in the dorsal root ganglia and sciatic nerve. Our findings suggest that FSN can effectively ameliorate peripheral neuropathic pain by regulate inflammation and endoplasmic reticulum stress, thereby determine its beneficial application in patients with peripheral nerve injuries.
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Axones , Estrés del Retículo Endoplásmico , Inflamación , Regeneración Nerviosa , Remielinización , Animales , Masculino , Inflamación/terapia , Inflamación/patología , Axones/fisiología , Humanos , Terapia por Acupuntura/métodos , Neuralgia/terapia , Nervio Ciático/lesiones , Persona de Mediana Edad , Femenino , Ratas , Ratas Sprague-Dawley , Modelos Animales de Enfermedad , AncianoRESUMEN
Nerve injury can not only lead to sensory and motor dysfunction, but also be complicated with neuropathic pain (NPP), which brings great psychosomatic injury to patients. At present, there is no effective treatment for NPP. Based on the functional characteristics of cell transplantation in nerve regeneration and injury repair, cell therapy has been used in the exploratory treatment of NPP and has become a promising treatment of NPP. In this article, we discuss the current mainstream cell types for the treatment of NPP, including Schwann cells, olfactory ensheathing cells, neural stem cells and mesenchymal stem cells in the treatment of NPP. These bioactive cells transplanted into the host have pharmacological properties of decreasing pain threshold and relieving NPP by exerting nutritional support, neuroprotection, immune regulation, promoting axonal regeneration, and remyelination. Cell transplantation can also change the microenvironment around the nerve injury, which is conducive to the survival of neurons. It can effectively relieve pain by repairing the injured nerve and rebuilding the nerve function. At present, some preclinical and clinical studies have shown that some encouraging results have been achieved in NPP treatment based on cell transplantation. Therefore, we discussed the feasible strategy of cell transplantation as a treatment of NPP and the problems and challenges that need to be solved in the current application of cell transplantation in NPP therapy.
Asunto(s)
Neuralgia , Neuralgia/terapia , Humanos , Animales , Trasplante de Células/métodos , Regeneración Nerviosa/fisiología , Células de Schwann/trasplanteRESUMEN
The study aimed to assess the analgesic effect of 10 Hz repetitive transcranial magnetic stimulation (rTMS) targeted to the prefrontal cortex (PFC) region on neuropathic pain (NPP) in rats with chronic constriction injury (CCI) of the sciatic nerve, and to investigate the possible underlying mechanism. Rats were randomly divided into three groups: sham operation, CCI, and rTMS. In the latter group, rTMS was applied to the left PFC. Von Frey fibres were used to measure the paw withdrawal mechanical threshold (PWMT). At the end of the treatment, immunofluorescence and western blotting were applied to detect the expression of M1 and M2 polarisation markers in microglia in the left PFC and sciatic nerve. ELISA was further used to detect the concentrations of inflammation-related cytokines. The results showed that CCI caused NPP in rats, reduced the pain threshold, promoted microglial polarisation to the M1 phenotype, and increased the secretion of pro-inflammatory and anti-inflammatory factors. Moreover, 10 Hz rTMS to the PFC was shown to improve NPP induced by CCI, induce microglial polarisation to M2, reduce the secretion of pro-inflammatory factors, and further increase the secretion of anti-inflammatory factors. Our data suggest that 10 Hz rTMS can alleviate CCI-induced neuropathic pain, while the underlying mechanism may potentially be related to the regulation of microglial M1-to-M2-type polarisation to regulate neuroinflammation.
Asunto(s)
Microglía , Neuralgia , Enfermedades Neuroinflamatorias , Corteza Prefrontal , Ratas Sprague-Dawley , Estimulación Magnética Transcraneal , Animales , Neuralgia/terapia , Neuralgia/metabolismo , Corteza Prefrontal/metabolismo , Masculino , Estimulación Magnética Transcraneal/métodos , Microglía/metabolismo , Enfermedades Neuroinflamatorias/terapia , Enfermedades Neuroinflamatorias/metabolismo , Nervio Ciático/lesiones , Umbral del Dolor/fisiología , Ratas , Modelos Animales de Enfermedad , Citocinas/metabolismoRESUMEN
Aim: To describe the successful treatment of atypical occipital neuralgia (ON) using a unilateral dual-lead occipital nerve stimulator.Setting: Outpatient clinic/operating room.Patient: A 53-year-old male with atypical ON.Case description: Patient was previously diagnosed with treatment-refractory left-sided trigeminal neuralgia with atypical occipital distribution. On presentation, his symptoms were consistent with ON with distribution to the left fronto-orbital area. He received a left-sided nerve stimulator implant targeting both the greater and lesser occipital nerves.Results: Patient reported pain relief from a numerical rating scale 10/10 to 3-4/10.Conclusion: ON with referred ipsilateral trigeminal distribution should be considered when patients present with simultaneous facial and occipital pain. Further, a dual-lead unilateral stimulator approach may be a viable treatment.
Atypical, persistent inflammation to the left occipital nerve treated with a neuromodulator: a case reportAim: To describe the successful treatment of atypical headache using a one-sided nerve stimulator.Setting: Outpatient clinic/operating room.Patient: A 53-year-old male with atypical headache.Case description: Patient was previously diagnosed with left-sided chronic facial pain with pain to the back of the head. He previously failed to improve with medication and underwent Botox injections and several surgical operations targeting the nerves responsible for his pain symptoms with no improvement. He recently underwent a nerve-stimulating device trial, designed to alter the activity levels of the targeted nerve, that targeted a nerve in the back of his head. This significantly improved his pain and he ultimately presented for an official stimulator implant. Upon presentation, his symptoms were consistent with left-sided headache to the back of the head with distribution to the left eye area.Results: Patient reported significant pain relief from 10/10 to a 3-4/10, with a 10 representing the worst pain the patient has ever felt.Conclusion: Left-sided headache on the back of the head that can distribute to the left eye area should be a consistent thought for pain/headache practitioners. Further, this stimulator placement approach may be a viable treatment.
Asunto(s)
Terapia por Estimulación Eléctrica , Neuralgia , Humanos , Masculino , Persona de Mediana Edad , Terapia por Estimulación Eléctrica/métodos , Terapia por Estimulación Eléctrica/instrumentación , Neuralgia/terapia , Neuralgia del Trigémino/terapia , Resultado del Tratamiento , Nervios EspinalesRESUMEN
STUDY DESIGN: A feasibility study. OBJECTIVES: Chronic neuropathic pain is a prevalent comorbidity in patients with spinal cord injury (SCI), and current medical treatments remain unsatisfactory. New developments as virtual walking are emerging which has been established and further developed at our centre. This study aims to investigate the feasibility of our virtual walking setup in a small group of SCI patients. SETTING: The study was conducted at the Swiss Paraplegic Centre in Nottwil, Switzerland. METHODS: Four patients aged 22 to 60 years were observed during and after therapy. Three had complete paraplegia (levels Th4-Th8) with neuropathic at- and below-level pain, while one had incomplete paraplegia (Th10) with at-level pain. The primary outcome measured was satisfaction with acceptance of and adherence to virtual walking therapy, alongside suggestions for therapy improvements. Additionally, patients kept a pain diary and pain drawings to measure the extent of pain distribution and intensity before and after therapy. Therapy schedules included either two sessions per week for five weeks or five sessions per week for two weeks. RESULTS: There was a sound satisfaction and good acceptance amongst participants. Support, duration, and number of sessions were perceived well and acceptable. Pain as a secondary outcome did not change during or after therapy in all but one patient which improved in pain intensity, pain quality as well as pain distribution. CONCLUSION: Results suggest that our virtual walking setting is a feasible tool that should be further studied in patients with SCI-related chronic neuropathic pain.