Pain
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Medication-overuse headache (MOH) is relatively common, but its incidence has not been calculated and there are no prospective population-based studies that have evaluated risk factors for developing MOH. The aim of this study was to estimate incidences of and identify risk factors for developing chronic daily headache (CDH) and MOH. This longitudinal population-based cohort study used data from the Nord-Trøndelag Health Surveys performed in 1995-1997 and 2006-2008. ⋯ In contrast, these factors did not increase the risk of CDHwoO. In this large population-based 11-year follow-up study, several risk factors for MOH did not increase the risk for CDHwoO, suggesting these are pathogenetically distinct. If the noted associations are causal, more focus on comorbid condition, physical activity, and use of tobacco and tranquilizers may limit the development of MOH.
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Critically ill pediatric patients frequently receive prolonged analgesia and sedation to provide pain relief and facilitate intensive care therapies. Iatrogenic withdrawal syndrome occurs when these drugs are stopped abruptly or weaned too rapidly. We investigated the validity and generalizability of the Withdrawal Assessment Tool-1 (WAT-1) in children during weaning of analgesics and sedatives. ⋯ Factor analyses confirmed that motor-related symptoms and behavioral state accounted for the most variance in WAT-1 scores. Supporting construct validity, cumulative opioid exposures were greater [40.2 (19.7-83.4) vs 17.6 (14.6-39.7) mg/kg, P=.004], length of opioid treatment before weaning was longer [7 (6-11) vs 5 (5-8)days, P=.004], and length of weaning from opioids was longer [10 (6-14) vs 6 (3-9)days, P=.008] in subjects with WAT-1 scores of ≥ 3 compared to subjects with WAT-1 scores of <3. The WAT-1 shows good psychometric performance and generalizability when used to assess clinically important withdrawal symptoms in pediatric intensive care and general ward settings.
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Although gender differences in pain and analgesia are well known, it still remains unclear whether men and women vary in response to multimodal pain treatment. This study was conducted to investigate whether men and women exhibited different outcomes after an intensive multimodal pain treatment program. The daily outpatient program consisted of individual treatment as well as group therapy, with a total amount of therapy of 117.5h per patient. ⋯ Consistently, women (ES .694) improved more in pain-related disabilities in daily life than men (ES .436). These distinctions are not due to differences in pain duration, received medication, psychiatric comorbidities, pain chronicity stage, or application for a disability pension. Therefore, gender differences not only refer to chronic pain prevalence, pain perception, or experimental pain measurement, but also seem to have a clinically relevant impact on the response to pain therapy.
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Peripheral injury or inflammation leads to a release of mediators capable of binding to a variety of ion channels and receptors. Among these are the 7-transmembrane receptors (G protein-coupled receptors) coupling to G(s), G(i/o), G₁₂/₁₃, or G(q/11) G proteins. Each of the G protein-coupled receptor pathways is involved in nociceptive modulation and pain processing, but the relative contribution of individual signaling pathways in vivo has not yet been worked out. ⋯ Surprisingly, our behavioral and electrophysiological experiments also indicated defects in basal mechanical sensitivity in G(q/11) mutant mice, suggesting a novel function for G(q/11) in tonic modulation of acute nociception. Patch-clamp recordings revealed changes in voltage-dependent tetrodotoxin-resistant and tetrodotoxin-sensitive sodium channels in nociceptors upon a loss of G(q/11), whereas potassium currents remained unchanged. Our results indicate that the functional role of the G(q)/G₁₁ branch of G-protein signaling in nociceptors in vivo not only spans sensitization mechanisms in pathological pain states, but is also operational in tonic modulation of basal nociception and acute pain.
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Osteoarthritis is a degenerative joint disease with pain and loss of joint function as major pathological features. Recent studies show that proteasome inhibitors reduce pain in various pathological conditions. We evaluated the effects of MG132, a reversible proteasome inhibitor on pain and joint destruction in a rat model of osteoarthritis. ⋯ Furthermore, the upregulated expression of MMP-3, SP, and CGRP in the arthritic rats was normalized by MG132 administration. We conclude that the proteasome inhibitor MG132 reduces pain and joint destruction, probably by involving the peripheral nervous system, and that changes in SP and CGRP expression correlate with alterations in behavioural responses. Our findings suggest that nontoxic proteasome inhibitors may represent a novel pharmacotherapy for osteoarthritis.