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The midbrain periaqueductal gray (PAG) plays a central role in pain modulation via descending pathways. Opioids and cannabinoids are thought to activate these descending pathways by relieving intrinsic GABAergic inhibition of PAG neurons which project to the rostroventromedial medulla (RVM), a process known as disinhibition. However, the PAG also receives descending extrinsic GABAergic inputs from the central nucleus of the amygdala (CeA) which are thought to inhibit PAG GABAergic interneurons. It remains unclear how opioids and cannabinoids act at these different synapses to control descending analgesic pathways. We used optogenetics, tract tracing and electrophysiology to identify the circuitry underlying opioid and cannabinoid actions within the PAG of male and female rats. It was observed that both RVM-projection and nonprojection PAG neurons received intrinsic-PAG and extrinsic-CeA synaptic inputs, which were predominantly GABAergic. Opioids acted via presynaptic µ-receptors to suppress both intrinsic and extrinsic GABAergic inputs onto all PAG neurons, although this inhibition was greater in RVM-projection neurons. By contrast, cannabinoids acted via presynaptic CB1 receptors to exclusively suppress the direct descending GABAergic input from the CeA onto RVM-projection PAG neurons. These findings indicate the CeA controls PAG output neurons which project to the RVM via parallel direct and indirect GABAergic pathways. While µ-opioids indiscriminately inhibit GABAergic inputs onto all PAG neurons, cannabinoids selectively inhibit a direct extrinsic GABAergic input from the amygdala onto PAG projection neurons. These differential actions of opioids and cannabinoids provide a flexible system to gate the descending control of analgesia from the PAG. The disinhibition hypothesis of analgesia states that opioids activate the midbrain periaqueductal gray (PAG) descending pathway by relieving the tonic inhibition of projection neurons from GABAergic interneurons. However, the PAG also receives extrinsic GABAergic inputs and is the locus of action of cannabinoid analgesics. Here, we show the relative sensitivity of GABAergic synapses to opioids and cannabinoids within the PAG depends on both the origin of presynaptic inputs and their postsynaptic targets. While opioids indiscriminately inhibit all GABAergic inputs onto all PAG neurons, cannabinoids selectively inhibit a direct extrinsic GABAergic input from the amygdala onto PAG descending projection neurons. These differential actions of opioids and cannabinoids provide a flexible system to gate PAG descending outputs.

Migraine, a common neurological disease, is known to impact the quality of life of individuals with this condition. We performed a systematic review with meta-analysis to investigate the abnormalities associated with executive functions of migraineurs as compared with healthy controls. In addition, we investigated the differences between patients with and without aura. A total of 25 studies were included in the systematic review and 19 in the meta-analysis. Meta-analysis was conducted using random effects models, with the unit of analysis as the standardised mean difference (calculated as Hedges'g). Patients with migraine had worse performance in the trail making test A (g = 0.40; 95% confidence interval [CI] 0.05-0.74;  = 0.0271) and B (g = 0.40; 95% CI 0.16-0.64;  = 0.0026), and digit span backward test (g = -0.20; 95% CI – 0.31, – 0.09;  = 0.0105). Subgroup analysis revealed no difference between migraine with and without aura. These results suggest that migraine patients may present worse performance for specific executive functional domains, including attention, working memory, and mental flexibility.

Physiotherapists trained to deliver biopsychosocial interventions for complex musculoskeletal pain problems often report difficulties in confidence and competency at the end of training. Cognitive Functional Therapy (CFT) is an individualized biopsychosocial intervention and understanding the facilitators and barriers to training in CFT will help inform future training programs. This study aimed to explore physiotherapists' and trainers' perceptions of the process of developing competency in CFT.

A-wave is a late response related either to demyelination or early axonal regeneration. It may be helpful in the evaluation of some peripheral neuropathies. In leprosy, previous studies suggested that A-waves could be a neurophysiological marker of pain in patients during reactions. Herein, we attempted to further assess the profile and clinical correlates of A-waves by exploring a large leprosy cohort.

The aim of this review is to characterize headache as a vaccine adverse event (VAE) in clinical trials.

The purpose of this review is to summarize advances in behavioral treatments for pain and headache disorders, as well as recent innovations in telemedicine for behavioral treatments.

This study was performed to evaluate trends in and provide future direction for anesthesiology education, research, and clinical practice.

The objectives of this study were to (1) report long-term health-related quality of life (HRQoL) outcomes among patients using rimegepant preventatively in BHV3000-305 (NCT03732638) open-label extension (OLE) and (2) map Migraine-Specific Quality of Life questionnaire version 2.1 (MSQv2) to EQ-5D-3L utility values over the double-blind treatment (DBT; 0-12 weeks) and the OLE (13-64 weeks) to assess the influence of treatment on these values.

Sural nerve neuroma is often caused by an injury during prior surgery, for example, osteosynthesis or ligament refixations at ankle level. Different surgical techniques to treat neuroma have been described. Neurectomy of an injured symptomatic sural nerve has been described as a treatment option for neuropathic pain. The aim of this study was to evaluate the outcomes of this technique to operatively treat sural nerve neuroma in our department.