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BACKGROUND: Only few previous cohort studies examined simultaneously predictors of chronic pain (CP) onset and recovery. Furthermore, these studies used various sociodemographic and pain-related characteristics, without standardized measures of sleep and depression. The present study aimed at expanding and strengthening these findings in a large Swiss population. METHODS: We analysed data from a longitudinal cohort (n = 4602) collected at two time points separated by 5 years in Lausanne, Switzerland. We studied through two independent multivariable logistic regression models, the predictors of CP onset and recovery, including socio-demographic data as well as standardized measures of sleep and mood. RESULTS: Chronic pain was reported by 43.1% and 44.4% of participants, with 11.6% at the second follow-up reporting moderate or intense pain. Neuropathic pain, regardless of intensity, had a more negative impact on quality of life. An inferential model (n = 1331) identified the male sex as predictive for recovering from CP. Older age, being overweight or obese (compared to normal weight), higher depression scores and pain medication intake were predictive for sustained pain at the second follow-up. A second model (n = 1886) identified being overweight or obese (compared to normal weight), low quality of sleep and being a former smoker (compared to a non-smoker) as predictive for developing CP, while the male sex was lowering the risk. CONCLUSIONS: While sex and weight are associated with both recovery and new CP onset, separate variables also need to be considered in these processes, underlining specific factors to be addressed, depending on the context, whether preventive or therapeutic. SIGNIFICANCE STATEMENT: Multivariable models in a Swiss cohort (N = 4602) associate male sex, not taking pain medication, normal weight, lower depression scores and younger age with recovery from chronic pain, while females, obese or overweight, having worse sleep and former smokers are associated with onset of new chronic pain. These common and separate factors need to be considered in treatment and prevention efforts.
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OBJECTIVE: To assess the bidirectional association between chronic pain and both subjectively and objectively measured physical activity (PA). DESIGN: Cross-sectional study. SETTING: Population-based sample in Lausanne, Switzerland, May 2014 to April 2017. PARTICIPANTS: Non-stratified, representative sample of the population of Lausanne (Switzerland) aged 35-75 years. Participants were excluded if they had missing data for the pain or the PA questionnaires, for accelerometry (defined as >20% of non-wear time or duration <7 days) or for covariates. PRIMARY OUTCOMES: Primary outcomes were association between chronic pain and previous, subjectively assessed PA (questionnaire), and subsequent, objectively assessed PA (accelerometry). Daily pain, pain duration, number of painful sites and pain intensity were assessed by questionnaire. PA was assessed by questionnaire 2 weeks prior and by accelerometry 2 weeks after completion of the pain questionnaire. PA was further categorised as sedentary (SED), light and moderate-to-vigorous PA. RESULTS: 2598 participants (52.9% women, mean age 60.5 years) had subjectively assessed PA. Multivariable analysis showed time spent in SED to be negatively associated with the number of painful sites: adjusted mean±SE 528±5, 522±7 and 502±7 min/day for 0, 1-2 and 3+ painful sites, respectively, p for trend <0.005. No other association was found between chronic pain and subjectively assessed PA categories. 2205 participants (52.8% women, mean age 61.7 years) had accelerometry-derived PA. No significant association between chronic pain and subsequent objectively assessed PA was found after multivariable analyses. CONCLUSION: In this Swiss population-based cohort, no consistent association was found between chronic pain and PA. Hence, in the general population, chronic pain does not significantly impact time spent in PA.
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Dor Crônica , Comportamento Sedentário , Acelerometria , Dor Crônica/epidemiologia , Estudos Transversais , Exercício Físico , Feminino , Humanos , Masculino , Pessoa de Meia-Idade , Suíça/epidemiologiaRESUMO
(1) Background: As membrane channels contribute to different cell functions, understanding the underlying mechanisms becomes extremely important. A large number of neuronal channels have been investigated, however, less studied are the channels expressed in the glia population, particularly in microglia. In the present study, we focused on the function of the Kv1.3, Kv1.5 and Kir2.1 potassium channels expressed in both BV2 cells and primary microglia cultures, which may impact the cellular migration process. (2) Methods: Using an immunocytochemical approach, we were able to show the presence of the investigated channels in BV2 microglial cells, record their currents using a patch clamp and their role in cell migration using the scratch assay. The migration of the primary microglial cells in culture was assessed using cell culture inserts. (3) Results: By blocking each potassium channel, we showed that Kv1.3 and Kir2.1 but not Kv1.5 are essential for BV2 cell migration. Further, primary microglial cultures were obtained from a line of transgenic CX3CR1-eGFP mice that express fluorescent labeled microglia. The mice were subjected to a spared nerve injury model of pain and we found that microglia motility in an 8 µm insert was reduced 2 days after spared nerve injury (SNI) compared with sham conditions. Additional investigations showed a further impact on cell motility by specifically blocking Kv1.3 and Kir2.1 but not Kv1.5; (4) Conclusions: Our study highlights the importance of the Kv1.3 and Kir2.1 but not Kv1.5 potassium channels on microglia migration both in BV2 and primary cell cultures.
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Movimento Celular , Canal de Potássio Kv1.3/metabolismo , Canal de Potássio Kv1.5/metabolismo , Microglia/citologia , Microglia/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Animais , Linhagem Celular , Fenômenos Eletrofisiológicos , Camundongos Transgênicos , Tecido Nervoso/lesões , Tecido Nervoso/patologiaRESUMO
Spinal microglia change their phenotype and proliferate after nerve injury, contributing to neuropathic pain. For the first time, we have characterized the electrophysiological properties of microglia and the potential role of microglial potassium channels in the spared nerve injury (SNI) model of neuropathic pain. We observed a strong increase of inward currents restricted at 2 days after injury associated with hyperpolarization of the resting membrane potential (RMP) in microglial cells compared to later time-points and naive animals. We identified pharmacologically and genetically the current as being mediated by Kir2.1 ion channels whose expression at the cell membrane is increased 2 days after SNI. The inhibition of Kir2.1 with ML133 and siRNA reversed the RMP hyperpolarization and strongly reduced the currents of microglial cells 2 days after SNI. These electrophysiological changes occurred coincidentally to the peak of microglial proliferation following nerve injury. In vitro, ML133 drastically reduced the proliferation of BV2 microglial cell line after both 2 and 4 days in culture. In vivo, the intrathecal injection of ML133 significantly attenuated the proliferation of microglia and neuropathic pain behaviors after nerve injury. In summary, our data implicate Kir2.1-mediated microglial proliferation as an important therapeutic target in neuropathic pain.
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Proliferação de Células/fisiologia , Microglia/metabolismo , Neuralgia/metabolismo , Bloqueadores dos Canais de Potássio/administração & dosagem , Canais de Potássio Corretores do Fluxo de Internalização/antagonistas & inibidores , Medula Espinal/metabolismo , Animais , Linhagem Celular Transformada , Proliferação de Células/efeitos dos fármacos , Células Cultivadas , Relação Dose-Resposta a Droga , Imidazóis/administração & dosagem , Injeções Espinhais , Masculino , Camundongos , Camundongos Transgênicos , Microglia/efeitos dos fármacos , Neuralgia/prevenção & controle , Fenantrolinas/administração & dosagem , Canais de Potássio Corretores do Fluxo de Internalização/biossíntese , Medula Espinal/citologia , Medula Espinal/efeitos dos fármacosRESUMO
The functioning of microglial cells inside the central nervous system depends on their ion channels expression. Microglia are capable of synthesizing different cytokines and chemokines, including CXCL1, and responding to their action via specific receptors. In this study, we explore the effect of intrathecal injection of CXCL1 on potassium currents, expressed in CX3CR1-Green Fluorescent Protein labeled microglia in transgenic mice. The results showed that CXCL1 hyperpolarized the cells by enhancing inward rectifying potassium currents and increasing the membrane area, suggesting an activating effect on microglia.
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Quimiocina CXCL1/administração & dosagem , Microglia/metabolismo , Canais de Potássio Corretores do Fluxo de Internalização/metabolismo , Animais , Receptor 1 de Quimiocina CX3C/genética , Proteínas de Fluorescência Verde/genética , Injeções Espinhais , Masculino , Camundongos , Camundongos Endogâmicos C57BL , Camundongos TransgênicosRESUMO
OBJECTIVE: Injection of opioids to the superior cervical ganglion (SCG) has been reported to provide pain relief in patients suffering from different kinds of neuropathic facial pain conditions, such as trigeminal neuralgia, postherpetic neuralgia, and atypical facial pain. The classic approach to the SCG is a transoral technique using a so-called "stopper" to prevent accidental carotid artery puncture. The main disadvantage of this technique is that the needle tip is positioned distant from the actual target, possibly impeding successful block of the SCG. A further limitation is that injection of local anesthetics due to potential carotid artery puncture is contraindicated. We hypothesized that the SCG can be identified and blocked using ultrasound imaging, potentially increasing precision of this technique. INTERVENTIONS: In this pilot study, 20 US-guided simulated blocks of the SCG were performed in 10 human cadavers in order to determine the accuracy of this novel block technique. After injection of 0.1 mL of dye, the cadavers were dissected to evaluate the needle position and coloring of the SCG. RESULTS: Nineteen of the 20 needle tips were located in or next to the SCG. This corresponded to a simulated block success rate of 95% (95% confidence interval 85-100%). In 17 cases, the SCG was completely colored, and in two cases, the caudal half of the SCG was colored with dye. CONCLUSIONS: The anatomical dissections confirmed that our ultrasound-guided approach to the SCG is accurate. Ultrasound could become an attractive alternative to the "blind" transoral technique of SCG blocks.