Association between chronic pain and physical activity in a Swiss population-based cohort: a cross-sectional study.

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.

Potassium Channels Kv1.3 and Kir2.1 But Not Kv1.5 Contribute to BV2 Cell Line and Primary Microglial Migration.

(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.

The inhibition of Kir2.1 potassium channels depolarizes spinal microglial cells, reduces their proliferation, and attenuates neuropathic pain.

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.

Intrathecal Administration of CXCL1 Enhances Potassium Currents in Microglial Cells.

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.

Block of the superior cervical ganglion, description of a novel ultrasound-guided technique in human cadavers.

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.