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Children of chronic pain patients run greater risk for developing chronic pain themselves. Exposure to chronic pain of the parent might install cognitive (e.g., pain catastrophizing, interpretation and attentional bias) and affective (e.g., pain anxiety) vulnerability which increase the risk for the development of chronic pain complaints in offspring. This study examines whether pain-free offspring of parents with chronic pain complaints make more health-threatening interpretations and display a stronger pain-related attentional bias compared to the offspring of pain-free parents. We furthermore examined differences between both groups on pain catastrophizing, pain anxiety, and somatic symptoms, and explored the relations between parental pain catastrophizing and aforementioned pain vulnerability measures in offspring.
Learn More >The McGill Pain Questionnaire (MPQ) pain quality descriptors have been analyzed to characterize the sensory, affective, and evaluative domains of pain, but have not been differentiated by pain location.
Learn More >Topical application of lidocaine and prilocaine (LP) cream attenuates the functionality of small cutaneous nerve fibers. The aim of this human study was to measure the underlying excitability modulation of small cutaneous nerve fibers using a novel and fast perception threshold tracking (PTT) technique.
Learn More >To determine if the perioperative administration of valproic acid reduces the incidence of chronic pain three months after amputation or revision surgery.
Learn More >The International Classification of Headache Disorders lists different subtypes of medication overuse headache (MOH), according to the medication overused. The aim of this study is to evaluate whether the different subtypes correspond to clinically distinguishable phenotypes in a large population.
Learn More >Post-traumatic headache (PTH) is a highly disabling secondary headache disorder and one of the most common sequelae of mild traumatic brain injury, also known as concussion. Considerable overlap exists between PTH and common primary headache disorders. The most common PTH phenotypes are migraine-like headache and tension-type-like headache. A better understanding of the pathophysiological similarities and differences between primary headache disorders and PTH could uncover unique treatment targets for PTH. Although possible underlying mechanisms of PTH have been elucidated, a substantial void remains in our understanding, and further research is needed. In this Review, we describe the evidence from animal and human studies that indicates involvement of several potential mechanisms in the development and persistence of PTH. These mechanisms include impaired descending modulation, neurometabolic changes, neuroinflammation and activation of the trigeminal sensory system. Furthermore, we outline future research directions to establish biomarkers involved in progression from acute to persistent PTH, and we identify potential drug targets to prevent and treat persistent PTH.
Learn More >To determine whether synchronous video-based telemedicine visits with specialists are feasible and to evaluate clinical effectiveness, patient perceptions, and other benefits of telemedicine visits for follow-up migraine care in a tertiary headache center.
Learn More >Detecting and avoiding noxious heat is crucial to prevent burn injury. While the nociceptor neurons involved in conveying heat-induced pain were identified more than a century ago, the molecular sensors responsible for detecting noxious heat had remained elusive. In a recent study, important progress was made in our understanding of the molecular basis of acute noxious heat sensing, with the identification of a set of three transient receptor potential (TRP) ion channels, TRPV1, TRPA1 and TRPM3, which have crucial but largely redundant roles in acute heat sensing. Most strikingly, combined elimination of all three TRP channels causes a complete loss of the acute avoidance reaction to noxious heat, without affecting pain responses to painful mechanical or cold stimuli. Here, we provide a brief account of the current model of acute noxious heat sensing, and discuss possible implications for analgesic drug development.
Learn More >AMP activated protein kinase (AMPK) is a multifunctional kinase that negatively regulates mechanistic target of rapamycin (mTOR) and mitogen activated protein kinase (MAPK) signaling, two signaling pathways that are linked to pain promotion after injury, such as surgical incision. AMPK can be activated directly using positive allosteric modulators as well as indirectly through the upregulation of upstream kinases such as liver kinase B1 (LKB1) which is a mechanism of action of metformin. Metformin's anti-hyperalgesic effects have been shown to occur only in male mice, raising questions about how metformin regulates pain sensitivity. We used metformin as well as other structurally distinct AMPK activators narciclasine, ZLN-024 and MK8722 to treat incision-induced mechanical hypersensitivity and hyperalgesic priming in male and female mice. We found that metformin was the only AMPK activator to have sex specific effects. We also found that indirect AMPK activators metformin and NCLS were able to reduce mechanical hypersensitivity and block hyperalgesic priming while direct AMPK activators, ZLN-024 and MK8722 only blocked priming. Direct and indirect AMPK activators stimulated AMPK in dorsal root ganglion (DRG) neuron cultures to a similar degree. However, incision decreased phosphorylated AMPK (p-AMPK) in DRG. Because AMPK phosphorylation is required for kinase activity, we interpret our findings as evidence that indirect AMPK activators are more effective for treating pain hypersensitivity after incision because they are able to drive increased p-AMPK through upstream kinases like LKB1. These findings have important implications for the development of AMPK-targeting therapeutics for pain treatment. SIGNIFICANCE STATEMENT: Non-opioid treatments for post-surgical pain are needed. Our work focused on whether direct or indirect AMPK activators would show greater efficacy for inhibiting incisional pain and also tested for potential sex differences. We conclude that indirect AMPK activators are likely to be more effective as potential therapeutics for post-surgical pain because they inhibit acute pain caused by incision and also prevent long-term neuronal plasticity that is involved in persistent post-surgical pain. Our work points to the natural product, indirect AMPK activator, narciclasine, as an excellent starting point for development of therapeutics.
Learn More >Addiction neuroscience models posit that recurrent drug use increases reactivity to drug-related cues and blunts responsiveness to natural rewards, propelling a cycle of hedonic dysregulation that drives addictive behavior. Here, we assessed whether a cognitive intervention for addiction, Mindfulness-Oriented Recovery Enhancement (MORE), could restructure reward responsiveness from valuation of drug-related reward back to valuation of natural reward. Before and after 8 weeks of MORE or a support group control, prescription opioid users ( = 135) viewed opioid and natural reward cues while an electroencephalogram biomarker of target engagement was assessed. MORE was associated with decreased opioid cue-reactivity and enhanced capacity to regulate responses to opioid and natural reward cues. Increased positive affective responses to natural reward cues were associated with decreased craving and mediated MORE's therapeutic effects on opioid misuse. This series of randomized experiments provide the first neurophysiological evidence that an integrative behavioral treatment can remediate hedonic dysregulation among chronic opioid users.
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