Pain
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Anti-nerve growth factor (anti-NGF) treatment is analgesic in chronic inflammatory pain conditions without reducing inflammation. Hypothesizing that ongoing pain induced by inflammatory mediators is increased by long term sensitization of nociceptors, we combined the non-inflammatory NGF-sensitization model with an inflammatory ultraviolet-B (UV-B) model in human volunteers. UV-B irradiation of the skin presensitized with NGF 3 weeks before intensified the pre-existing NGF hyperalgesia during the inflammatory phase of UV-B and caused spontaneous pain in about 70% of the subjects. ⋯ Hyperalgesia and spontaneous pain coexisted in NGF/UV-B treated skin but did not significantly correlate (r < -0.1 at day 1 and r < 0.2 at day 3). We conclude that NGF can sensitize nociceptive endings such that inflammatory mediators may cause sufficient excitation to provoke spontaneous pain. Our results suggest that neuronal sensitization and level of inflammation represent independent therapeutic targets in chronic inflammatory pain conditions.
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Opioid therapy offers the promise of reducing the burden of chronic pain in not just individual patients, but among the broad population of patients with chronic pain. Randomized trials have demonstrated that opioid therapy for up to 12-16weeks is superior to placebo, but have not addressed longer-term use. In the United States, opioid sales have quadrupled during 2000-2010, with parallel increases in opioid accidental overdose deaths and substance abuse admissions. ⋯ Long-term opioid therapy appears to be associated with iatrogenic harm to the patients who receive the prescriptions and to the general population. The United States has, in effect, conducted an experiment of population-wide treatment of chronic pain with long-term opioid therapy. The population-wide benefits have been hard to demonstrate, but the harms are now well demonstrated.
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Chemotherapy-induced neuropathy (CIN) is an adverse effect of chemotherapy. Pain in CIN might comprise neuropathic and nonneuropathic (ie, musculoskeletal) pain components, which might be characterized by pain patterns, electrophysiology, and somatosensory profiling. Included were 146 patients (100 female, 46 male; aged 56 ± 0.8 years) with CIN arising from different chemotherapy regimens. ⋯ The detrimental effect of chemotherapy on large fibres failed to differentiate painful from painless CIN. Patients stratified for musculoskeletal or neuropathic pain, however, differed in psychological and somatosensory parameters. This stratification might allow for the application of a more specific therapy.
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Hundreds of genes are proposed to contribute to nociception and pain perception. Historically, most studies of pain-related genes have examined them in isolation or alongside a handful of other genes. More recently the use of systems biology techniques has enabled us to study genes in the context of the biological pathways and networks in which they operate. ⋯ The Web site can be used to find out more about a gene of interest by looking at the function of its interaction partners. It can also be used to interpret the results of a functional genomics experiment by revealing putative novel pain-related genes that have similar expression patterns to known pain-related genes and by ranking genes according to their network connections with known pain genes. We expect this resource to grow over time and become a valuable asset to the pain community.
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Although feverfew has been used for centuries to treat pain and headaches and is recommended for migraine treatment, the mechanism for its protective action remains unknown. Migraine is triggered by calcitonin gene-related peptide (CGRP) release from trigeminal neurons. Peptidergic sensory neurons express a series of transient receptor potential (TRP) channels, including the ankyrin 1 (TRPA1) channel. ⋯ This effect of parthenolide abrogates nociceptive responses evoked by stimulation of peripheral trigeminal endings. TRPA1 targeting and neuronal desensitization by parthenolide inhibits CGRP release from trigeminal neurons and CGRP-mediated meningeal vasodilatation, evoked by either TRPA1 agonists or other unspecific stimuli. TRPA1 partial agonism, together with desensitization and nociceptor defunctionalization, ultimately resulting in inhibition of CGRP release within the trigeminovascular system, may contribute to the antimigraine effect of parthenolide.