Pain
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We investigated the efficacy of inhibiting persistent Na + currents (I NaP ) in acute rodent models of migraine with aura. Cortical spreading depression (SD) is a slow wave of neuronal and glial depolarization that underlies the migraine aura. Minimally invasive optogenetic SD (opto-SD) causes periorbital mechanical allodynia in mice, suggesting SD activates trigeminal nociceptors. ⋯ GS-458967 also diminished early and late phase formalin-induced paw-licking behavior with early phase paw licking responding to lower doses. GS-458967 up to 3 mg/kg had no impact on locomotor activity. These data provide evidence that I NaP inhibition can reduce opto-SD-induced trigeminal pain behavior and support I NaP inhibition as an antinociceptive strategy for both abortive and preventive treatment of migraine.
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Historical Article
Introduction and a brief historical overview of the International Association for the Study of Pain.
The mission of the International Association for the Study of Pain (IASP) is "to bring together scientists, clinicians, healthcare providers, and policymakers to stimulate and support the study of pain and to translate that knowledge into improved pain relief worldwide." The IASP will celebrate its 50th anniversary next year, and the series of articles published in this special issue of its flagship journal PAIN highlights the IASP's achievements over the past 5 decades. This article provides a brief historical overview of the IASP's 50-year journey, including the key "players," events, and initiatives leading to its formation and contributing to its progress. It complements the other articles outlining the contributions that the IASP has made and likely will continue to make to advances in pain education, research, management and advocacy, and its value to the IASP members.
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Multicenter Study
Brain morphology predicts individual sensitivity to pain: a multicenter machine learning approach.
Sensitivity to pain shows a remarkable interindividual variance that has been reported to both forecast and accompany various clinical pain conditions. Although pain thresholds have been reported to be associated to brain morphology, it is still unclear how well these findings replicate in independent data and whether they are powerful enough to provide reliable pain sensitivity predictions on the individual level. In this study, we constructed a predictive model of pain sensitivity (as measured with pain thresholds) using structural magnetic resonance imaging-based cortical thickness data from a multicentre data set (3 centres and 131 healthy participants). ⋯ Analysis of model coefficients suggests that the most robust cortical thickness predictors of pain sensitivity are the right rostral anterior cingulate gyrus, left parahippocampal gyrus, and left temporal pole. Cortical thickness in these regions was negatively correlated to pain sensitivity. Our results can be considered as a proof-of-concept for the capacity of brain morphology to predict pain sensitivity, paving the way towards future multimodal brain-based biomarkers of pain.
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Chronic pelvic pain (CPP), despite its high prevalence, is still relatively poorly understood mechanistically. This study, as part of the Translational Research in Pelvic Pain (TRiPP) project, has used a full quantitative sensory testing (QST) paradigm to profile n = 85 women with and without CPP (endometriosis or bladder pain specifically). We used the foot as a control site and abdomen as the test site. ⋯ The data suggest that participants with CPP are sensitive to both deep tissue and cutaneous inputs, suggesting that central mechanisms may be important in this cohort. We also see phenotypes such as thermal hyperalgesia, which may be the result of peripheral mechanisms, such as irritable nociceptors. This highlights the importance of stratifying patients into clinically meaningful phenotypes, which may have implications for the development of better therapeutic strategies for CPP.