Pain
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Orphenadrine is a drug acting on multiple targets, including muscarinic, histaminic, and NMDA receptors. It is used in the treatment of Parkinson's disease and in musculoskeletal disorders. It is also used as an analgesic, although its mechanism of action is still unknown. ⋯ Orphenadrine affinities for resting and inactivated sodium channels were higher compared to those of known sodium channels blockers, such as mexiletine and flecainide. Low, clinically relevant orphenadrine concentration produces a significant block of Nav1.7, Nav1.8, and Nav1.9 channels, which are critical for experiencing pain sensations, indicating a role for sodium channel blockade in the clinical efficacy of orphenadrine as analgesic compound. On the other hand, block of Nav1.1 and Nav1.5 may contribute to the proconvulsive and proarrhythmic adverse reactions, especially observed during overdose.
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Randomized Controlled Trial
A randomized, placebo-controlled trial of oxycodone and of gabapentin for acute pain in herpes zoster.
Although acute pain in patients with herpes zoster can be severe and has a substantial impact on health-related quality of life, there have been no randomized clinical trials of oral medications specifically for its ongoing treatment. A randomized clinical trial was conducted in which 87 subjects >or=50 years of age with herpes zoster within 6 calendar days of rash onset and with worst pain in the past 24h >or=3 on a 0-10 rating scale initiated 7 days of treatment with famciclovir in combination with 28 days of treatment with either controlled-release (CR) oxycodone, gabapentin, or placebo. Subjects were evaluated for adverse effects of treatment, acute pain, and health-related quality of life. ⋯ Treatment with CR-oxycodone reduced the mean worst pain over days 1-8 (p=0.01) and days 1-14 (p=0.02) relative to placebo but not throughout the entire 28-day treatment period as pain resolved in most subjects. Gabapentin did not provide significantly greater pain relief than placebo, although the data for the first week were consistent with a modest benefit. By demonstrating that CR-oxycodone is safe, generally adequately tolerated, and appears to have efficacy for relieving acute pain, the results of this clinical trial provide a foundation for evidence-based treatment for acute pain in herpes zoster.
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Randomized Controlled Trial Clinical Trial
Cost effectiveness of two rehabilitation programmes for neck and back pain patients: A seven year follow-up.
The cost effectiveness of work-oriented rehabilitation for persons on long-term sick leave needs to be assessed. This prospective observational study presents a follow-up seven years after rehabilitation using two different evidence-based work-oriented regimens. Individuals on sick leave for neck and back pain were referred to two rehabilitation programmes in Sweden. ⋯ The results of this study show that MPD but not OMTP achieves the goal of working life-oriented rehabilitation. A direct comparison between the rehabilitation programmes strengthened the assumption that long-term sickness absence prior to rehabilitation is associated with more days on sick leave after rehabilitation. This analysis also indicated the importance of participants' pain self-efficacy beliefs and recovery beliefs on rehabilitation outcome.
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Randomized Controlled Trial
A randomized clinical trial of a brief hypnosis intervention to control venepuncture-related pain of paediatric cancer patients.
Venepuncture for blood sampling can be a distressing experience for a considerable number of children. A prospective controlled trial was conducted to compare the efficacy of a local anaesthetic (EMLA) with a combination of EMLA with self-hypnosis in the relief of venepuncture-induced pain and anxiety in 45 paediatric cancer outpatients (age 6-16years). A secondary aim of the trial was to test whether the intervention will have a beneficial effect on parents' anxiety levels during their child's procedure. ⋯ The therapeutic benefit of the brief hypnotic intervention was maintained in the follow-up. The present findings are particularly important in that this study was a randomized, controlled trial conducted in a naturalistic medical setting. In this context, convergence of subjective and objective outcomes was reached with large effect sizes that were consistently supportive of the beneficial effects of self-hypnosis, an intervention that can be easily taught to children, is noninvasive and poses minimal risk to young patients and their parents.
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TNFalpha plays a pivotal role in rheumatoid arthritis (RA) but little is known of the mechanisms that link the inflammatory and nociceptive effects of TNFalpha. We have established a murine model of TNFalpha-induced TRPV1-dependent bilateral thermal hyperalgesia that then allowed us to identify distinct peripheral mechanisms involved in mediating TNFalpha-induced ipsilateral and contralateral hyperalgesia. Thermal hyperalgesia and inflammation were assessed in both hindpaws following unilateral intraplantar (i.pl.) TNFalpha. ⋯ However, TNFalpha-induced IL-1beta generation in both paws and the presence of local IL-1beta in the contralateral paw were essential for the development of bilateral hyperalgesia. These results identify a series of peripheral events through which TNFalpha triggers and maintains bilateral inflammatory pain. This potentially allows a better understanding of mechanisms involved in TNFalpha-dependent pain pathways in symmetrical diseases such as arthritis.