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Facial pain, alone or combined with other symptoms, is a frequent complaint. Moreover, it is a symptom situated at, more than any other pain condition, a crosspoint where several disciplines meet, for example, dentists; manual therapists; ophthalmologists; psychologists; and ear-nose-throat, pain, and internal medicine physicians besides neurologists and neurosurgeons. Recently, a new version of the most widely used classification system among neurologists for headache and facial pain, the International Classification of Headache Disorders, has been published.
Learn More >Effective, inexpensive, and low-risk interventions are needed for patients with nonspecific persistent low back pain (NS-PLBP) who are unresponsive to primary care interventions. Cognitive functional therapy (CFT) is a multidimensional behavioral self-management approach that has demonstrated promising results in primary care and has not been tested in secondary care.
Learn More >Chronic prescription opioid use is a major international public health issue associated with significant harms, including increased risk of hospitalisation, morbidity and death. Guidance for healthcare professionals on when and how to deprescribe or reduce opioids is required. A key step for guideline development for deprescribing pharmacotherapy is to understand the perspectives of stakeholders. The aim of this study was to explore the perspectives of healthcare professional stakeholders on the challenges associated with opioid deprescribing and factors to be considered in the development of opioid deprescribing guidelines.
Learn More >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.
Learn More >The inflammatory/immune response at the site of peripheral nerve injury participates in the pathophysiology of neuropathic pain. Nevertheless, little is known about the local regulatory mechanisms underlying peripheral nerve injury that counteract the development of pain. Here, we investigated the contribution of regulatory T (Treg) cells to the development of neuropathic pain by using a partial sciatic nerve ligation model (PSNL) in mice. We showed that Treg cells infiltrate and proliferate in the site of peripheral nerve injury. Local Treg cells suppressed the development of neuropathic pain mainly through the inhibition of the CD4 Th1 response. Treg cells also indirectly reduced neuronal damage and neuroinflammation at the level of the sensory ganglia. Finally, we identified IL-10 signaling as an intrinsic mechanism by which Treg cells counteract neuropathic pain development. These results revealed Treg cells as important inhibitory modulators of the immune response at the site of peripheral nerve injury that restrain the development of neuropathic pain. In conclusion, the boosting of Treg cell function/activity might be explored as a possible interventional approach to reduce neuropathic pain development after peripheral nerve damage.
Learn More >Cell-based assays comprising primary sensory neurons cultured in vitro are an emerging tool for the screening and identification of potential analgesic compounds and chronic pain treatments. High-content screening (HCS) platforms for drug screening are characterized by a measure of assay quality indicator, such as the Z'-factor, which considers the signal dynamic range and data variation using control compounds only. Although widely accepted as a quality metric in high throughput screening (HTS), standard Z'-factor are not well-suited to indicate the quality of complex cell-based assays.
Learn More >Migraine and stroke are two common and heterogeneous neurovascular disorders responsible for a significant burden for those affected and a great economic cost for the society. There is growing evidence that migraine increases the overall risk of cerebrovascular diseases. In this review, based on available literature through a PubMed search, we found that ischaemic stroke in people with migraine is strongly associated with migraine with aura, young age, female sex, use of oral contraceptives and smoking habits. The risk of transient ischaemic attack also seems to be increased in people with migraine, although this issue has not been extensively investigated. Although migraine appears to be associated with haemorrhagic stroke, the migraine aura status has a small influence on this relationship. Neuroimaging studies have revealed a higher prevalence of asymptomatic structural brain lesions in people with migraine. They are also more likely to have unfavourable vascular risk factors; however, the increased risk of stroke seems to be more apparent among people with migraine without traditional risk factors. The mechanism behind the migraine-stroke association is unknown. In light of the higher risk of stroke in people with migraine with aura, it is important to identify and modify any vascular risk factor. There is currently no direct evidence to support that a migraine prophylactic treatment can reduce future stroke in people with migraine.
Learn More >Anterior cingulate cortex (ACC) plays important roles in sensory perception including pain and itch. Neurons in the ACC receive various neuromodulatory inputs from subcortical structures, including locus coeruleus noradrenaline (LC-NA) neurons. Few studies have been reported about synaptic and behavioral functions of LC-NA projections to the ACC. Using viral-genetic method (AAV-DIO-eYFP) on DBH-cre mice, we found that LC-NA formed synaptic connections to ACC pyramidal cells but not interneurons. This is further supported by the electron microscopic study showing NAergic fibers contact the presynaptic inputs and post-synaptic areas of the pyramidal cells. NA application produced both pre- and post-synaptic potentiation effects in ACC excitatory transmission in vivo and in vitro. Activation of LC-NA projection to the ACC by optogenetic method produced enhancement of excitatory transmission in vitro and induced scratching and behavioral sensitization for mechanical stimulation. Our results demonstrate that LC-NA projections enhance or facilitate brain responses to pain and itch by potentiating glutamatergic synaptic transmissions in the ACC.
Learn More >Neuropathic pain severely impairs rehabilitation and quality of life after spinal cord injury (SCI). The sphingosine-1-phosphate receptor agonist FTY720 plays an important protective role in neuronal injury. This study aims to examine the effects of FTY720 in a rat acute SCI model, focusing on neuropathic pain. Female rats with SCI induced by 1-minute clip compression were administered vehicle or 1.5 mg/kg of FTY720 24 hours after the injury. Using the mechanical nociceptive threshold test, we monitored neuropathic pain and performed histological analysis of the pain pathway, including the opioid receptor (MOR), hydroxytryptamine transporter (HTT), and calcitonin gene-related peptide (CGRP). The motor score, SCI lesion volume, residual motor axons, inflammatory response, glial scar, and microvascular endothelial dysfunction were also compared between the two groups. FTY720 treatment resulted in significant attenuation of post-traumatic neuropathic pain. It also decreased systemic and local inflammation, thereby reducing the damaged areas and astrogliosis and resulting in motor functional recovery. While there was no difference in the CGRP expression between the two groups, FTY720 significantly preserved the MOR in both the caudal and rostral areas of the spinal dorsal horn. While HTT was preserved in the FTY720 group, it was significantly increased in the rostral side and decreased in the caudal side of the injury in the vehicle group. These results suggest that FTY720 ameliorates post-traumatic allodynia through regulation of neuro-inflammation, maintenance of the blood brain barrier, and inhibition of glial scar formation, thereby preserving the connectivity of the descending inhibitory pathway and reducing neuropathic pain.
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