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Corneal Confocal Microscopy Demonstrates Corneal Nerve Loss in Patients With Trigeminal Neuralgia.

The diagnosis of trigeminal neuralgia (TN) is challenging due to the lack of objective diagnostics. Corneal confocal microscopy (CCM) is a non-invasive ophthalmic imaging technique, which allows quantification of corneal nerve fibers arising from the trigeminal ganglion and may allow the assessment of neurodegeneration in TN. CCM was undertaken in 11 patients with TN and 11 age-matched healthy controls. Corneal nerve fiber density (CNFD), corneal nerve branch density, corneal nerve fiber length (CNFL), corneal nerve fiber width, corneal nerve fiber area, and dendritic cell and non-dendritic cell density with or without nerve fiber contact were quantified. Patients with TN had significantly lower CNFD and CNFL but no difference for any other corneal nerve or dendritic cell parameter in the ipsilateral and the contralateral cornea compared to the control group. There was no significant difference in corneal nerve and cell parameters between patients with TN with and without involvement of the ophthalmic nerve (V1) or with nerve vessel conflict. Corneal confocal microscopy is a rapid non-invasive imaging technique that identifies symmetrical corneal nerve loss in patients with TN.

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Novel TRPV1 Channel Agonists With Faster and More Potent Analgesic Properties Than Capsaicin.

The transient receptor potential vanilloid 1 (TRPV1) ion channel is a member of the family of Transient Receptor Potential (TRP) channels that acts as a molecular detector of noxious signals in primary sensory neurons. Activated by capsaicin, heat, voltage and protons, it is also well known for its desensitization, which led to the medical use of topically applied TRPV1 agonist capsaicin for its long-lasting analgesic effects. Here we report three novel small molecules, which were identified using a Structure-Based Virtual Screening for TRPV1 from the ZINC database. The three compounds were tested using electrophysiological assays, which confirmed their capsaicin-like agonist activity. von Frey filaments were used to measure the analgesic effects of the compounds applied topically on tactile allodynia induced by intra-plantar carrageenan. All compounds had anti-nociceptive activity, but two of them showed faster and longer lasting analgesic effects than capsaicin. The present results suggest that TRPV1 agonists different from capsaicin could be used to develop topical analgesics with faster onset and more potent effects.

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The Efficacy of Nerve Growth Factor Antibody for the Treatment of Osteoarthritis Pain and Chronic Low-Back Pain: A Meta-Analysis.

Nerve growth factor (NGF) plays a crucial role in pain modulation and is being considered as a new therapeutic target for pain therapy. The purpose of this meta-analysis was to study the efficacy of anti-NGF antibodies for the treatment of osteoarthritis pain and chronic low-back pain, and to provide evidence and direction for further research and practice.

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Chronic Pain, Mood Disorders and Substance Use: Outcomes of Interdisciplinary Care in a Residential Psychiatric Hospital.

The objective is to report outcomes of an interdisciplinary group-based residential chronic pain recovery program (CPRC), located in a private non-profit psychiatric hospital. The chronic pain program was aimed at treatment and engagement in self-care of both pain and co-occurring disorders in a residential facility that also offered treatment for specific psychiatric disorders.

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Enhanced pain-related conditioning for face compared to hand pain.

Pain is evolutionarily hardwired to signal potential danger and threat. It has been proposed that altered pain-related associative learning processes, i.e., emotional or fear conditioning, might contribute to the development and maintenance of chronic pain. Pain in or near the face plays a special role in pain perception and processing, especially with regard to increased pain-related fear and unpleasantness. However, differences in pain-related learning mechanisms between the face and other body parts have not yet been investigated. Here, we examined body-site specific differences in associative emotional conditioning using electrical stimuli applied to the face and the hand. Acquisition, extinction, and reinstatement of cue-pain associations were assessed in a 2-day emotional conditioning paradigm using a within-subject design. Data of 34 healthy subjects revealed higher fear of face pain as compared to hand pain. During acquisition, face pain (as compared to hand pain) led to a steeper increase in pain-related negative emotions in response to conditioned stimuli (CS) as assessed using valence ratings. While no significant differences between both conditions were observed during the extinction phase, a reinstatement effect for face but not for hand pain was revealed on the descriptive level and contingency awareness was higher for face pain compared to hand pain. Our results indicate a stronger propensity to acquire cue-pain-associations for face compared to hand pain, which might also be reinstated more easily. These differences in learning and resultant pain-related emotions might play an important role in the chronification and high prevalence of chronic facial pain and stress the evolutionary significance of pain in the head and face.

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The role of erenumab in the treatment of migraine.

Calcitonin gene related peptide (CGRP) monoclonal antibodies (mAbs) have been the first class of specifically developed preventive treatments for migraine. Clinical trials data suggest superiority of the CGRP mAbs to placebo in terms of prevention of migraine symptoms, migraine-specific quality of life and headache related disability. Treatment-related side effects overall did not differ significantly from placebo and discontinuation rate due to side effects has been low across the clinical trials, perhaps in view of their peripheral mode of action. Along with their route and frequency of administration, these novel class of drugs may constitute an improvement compared with the established arsenal of migraine treatments. Erenumab is a fully human antibody and the only mAb acting on the CGRP pathway by blocking its receptor. It is the first of the CGRP mAb class approved by the US Food and Drug Administration (May 2018) and the European Medicines Agency (July 2018). Erenumab exists in two different doses (70 mg and 140 mg) and it is administered with monthly subcutaneous injections. This review summarises erenumab pharmacological characteristics, clinical trials data, focusing on the potential role of this treatment in clinical practice.

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Sex-Specific Impact of Pain Severity, Insomnia, and Psychosocial Factors on Disability due to Spinal Degenerative Disease.

Pain experience due to spinal degenerative disease decreases activity of daily living and quality of life. The present cross-sectional study was aimed at examining the sex-specific impact of pain severity, psychosocial factors, and insomnia on the disability due to chronic pain arising from spinal degenerative disease.

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Percutaneous Bioelectric Current Stimulation for Chronic Cluster Headache – A Possible Transformative Approach to Cluster Headache.

Cluster headache (CH) is considered to be a catastrophic disease presenting the most severe human pain condition. Available pharmacological treatments are hampered by unwanted side effects, and there is an urgent need for non-pharmacological treatment alternatives. We present a novel therapeutic approach for chronic CH, having evolved from an episodic CH, using a non-invasive percutaneous bioelectric current stimulation (PBCS), which generates static electric fields in the range of the naturally occurring electric potentials.

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Pregabalin as a Pain Therapeutic: Beyond Calcium Channels.

Initially developed to generate new treatments for epilepsy, gabapentin, and pregabalin ("gabapentinoids") were engineered to mimic the action of GABA and to modulate GABA metabolism. Rather than their intended pharmacological action on GABA neurotransmission, instead, they exhibit a high affinity for the α2δ-1 and α2δ-2 subunits of voltage-activated calcium channels, wherein binding of gabapentinoids inhibits cellular calcium influx and attenuates neurotransmission. Despite a lack of activity on GABA levels, gabapentin and pregabalin are effective at suppressing seizures and subsequently approved as a new class of antiepileptic therapy for partial-onset epilepsy. Through the same hypothesized molecular mechanism and by controlling neuronal hyperexcitability, gabapentinoids demonstrate clear efficacy in pain management, which has arguably been their most extensively prescribed application to date. In this review, we focus on pregabalin as a second-generation gabapentinoid widely employed in the treatment of a variety of pain conditions. We also discuss the wider functional roles of α2δ subunits and the contributions that pregabalin might play in affecting physiological and pathophysiological processes.

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Predicting EQ-5D-5L Utility Scores from the Oswestry Disability Index and Roland-Morris Disability Questionnaire for Low Back Pain.

Cost utility analysis is important for measuring the impact of chronic disease and helps clinicians and policymakers in patient management and policy decisions, but generic preference-based measures are not always considered in clinical studies.

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