Accepted

Microglia are important mediators of neuroinflammation, which underlies neuropathic pain. However, the molecular checkpoints controlling microglial reactivity are not well-understood. Here, we investigated the role of Orai1 channels for microglia-mediated neuroinflammation following nerve injury and find that deletion of Orai1 in microglia attenuates Ca signaling and the production of inflammatory cytokines by proalgesic agonists. Conditional deletion of Orai1 attenuated microglial proliferation in the dorsal horn, spinal cytokine levels, and potentiation of excitatory neurotransmission following peripheral nerve injury. These cellular effects were accompanied by mitigation of pain hyperalgesia in microglial Orai1 knockout mice. A small-molecule Orai1 inhibitor, CM4620, similarly mitigated allodynia in male mice. Unexpectedly, these protective effects were not seen in female mice, revealing sexual dimorphism in Orai1 regulation of microglial reactivity and hyperalgesia. Together, these findings indicate that Orai1 channels are key regulators of the sexually dimorphic role of microglia for the neuroinflammation that underlies neuropathic pain.

We prospectively performed the Itoigawa Headache Awareness Campaign from August 2021 to June 2022, with two main interventions, and evaluated its effectiveness.

We hypothesized that the response of trigeminal dermal blood flow (DBF) in the trigeminal system and consecutive expansion of flare response to capsaicin would differ from the somatosensory system (arm). We also investigated whether there are differences between patients with migraine and healthy controls (HC).

Dysfunctional sensory processing is described in migraine. This study aimed to evaluate visual perception in patients with migraine without aura using the visual temporal discrimination (VTD) test.

To assess whether migraine may be genetically and/or causally associated with inflammatory bowel disease (IBD) or celiac disease.

To investigate whether sensory sensitivity is associated with the perceived severity of Visual Snow Syndrome (VSS) symptoms.

To assess the clinical efficacy of remote electrical neuromodulation (REN), used every other day, for the prevention of migraine.

Surface electromyography-biofeedback (sEMG-BF) may reduce the burden of CLBP by improving physical functioning, sleep, pain catastrophizing, anxiety, and depression. This qualitative study investigated the impact of weekly EMG-BF sessions on adults with CLBP.

There has been both great interest in and skepticism about the strategies for headache inhibition in patients with patent foramen ovale and migraines (PFO-migraine). Furthermore, many questions remain about the fundamental pathophysiology of PFO-migraines. Herein, the inhibiting effect of normobaric oxygenation (NBO) on PFO-migraine was analyzed.

Chronic pain begins with acute pain. Physicians tend to classify pain by duration (acute vs chronic) and mechanism (nociceptive, neuropathic and nociplastic). Although this taxonomy may facilitate diagnosis and documentation, such categories are to some degree arbitrary constructs, with significant overlap in terms of mechanisms and treatments. In clinical practice, there are myriad different definitions for chronic pain and a substantial portion of chronic pain involves mixed phenotypes. Classification of pain based on acuity and mechanisms informs management at all levels and constitutes a critical part of guidelines and treatment for chronic pain care. Yet specialty care is often siloed, with advances in understanding lagging years behind in some areas in which these developments should be at the forefront of clinical practice. For example, in perioperative pain management, enhanced recovery protocols are not standardized and tend to drive treatment without consideration of mechanisms, which in many cases may be incongruent with personalized medicine and mechanism-based treatment. In this educational document, we discuss mechanisms and classification of pain as it pertains to commonly performed surgical procedures. Our goal is to provide a clinical reference for the acute pain physician to facilitate pain management decision-making (both diagnosis and therapy) in the perioperative period.