European journal of pain : EJP
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Fixed-dose combination analgesics are used widely, and available both on prescription and over-the-counter. Combination drugs should provide more analgesia than with any single drug in the combination, but there is no evidence in humans about whether oral combinations have just additive effects, or are synergistic or even subadditive. We suggest that the measured result for the combination would be the summation of the absolute benefit increase (effect of active drug minus effect of placebo) of each component of a combination if effects were (merely) additive, and greater than the sum of the absolute benefits if they were synergistic. ⋯ Results showed that expected numbers needed to treat (NNT) for additive effects were generally within the 95% confidence interval of measured NNTs. This was true for combinations of paracetamol plus ibuprofen and paracetamol plus opioids in acute pain, and naproxen plus sumatriptan in migraine, but not where efficacy was very low or very high, nor combinations of paracetamol plus dextropropoxyphene. There was no evidence of synergy, defined as supra-additive effects.
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Randomized Controlled Trial
Dose response of tramadol and its combination with paracetamol in UVB induced hyperalgesia.
Combining tramadol with paracetamol is an established analgesic treatment strategy. However, dosing and differential effects on peripheral and central hyperalgesia are still to be determined. After Ethics Committee approval, 32 volunteers have been included in this 2 phased, double blinded, placebo controlled, cross-over study. ⋯ Paracetamol also reduced secondary hyperalgesia, but no combination effect with tramadol could be shown. We conclude, in inflammatory hyperalgesia tramadol alone exerts only weak anti-hyperalgesia. Even adding a small dose paracetamol enhances thermal anti-hyperalgesia.
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Multicenter Study
Using graded motor imagery for complex regional pain syndrome in clinical practice: failure to improve pain.
There is good evidence from studies conducted in a single-centre research setting for the efficacy of graded motor imagery (GMI) treatment, a complex physiotherapy intervention, to reduce pain in long-standing complex regional pain syndrome (CRPS). However, whether GMI is effective in clinical practice is not established. ⋯ The failure of our real-world implementation of GMI suggests that better understanding of both the GMI methodology and its interaction with other treatment methods is required to ensure that GMI research results can be translated into clinical practice. Our results highlight challenges with the translation of complex interventions for chronic pain conditions into clinical practice.
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Widespread pain (WSP) is common in the general population and is associated with poor outcomes. The aim of this study was to quantify the risk for medically certified disability pension from WSP. We further studied how other common physical symptoms, common mental disorders and functional limitations influenced this risk. ⋯ Further adjustments for other common symptoms, including mental illness, reduced, but did not abolish these risks. WSP is a major risk factor for disability pensions, and not only pensions for musculoskeletal disorders. The global impact of WSP, and its close association to other symptoms, suggests prevention of the severe occupational outcomes for this group must have a broad focus and move beyond symptom directed approaches.
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Pain influences many aspects of daily living and effective analgesics should reinstate normal spontaneous daily behaviours. Experiments are described herein which show that the innate, spontaneous behaviour of burrowing by rats, which can be simply and objectively assessed by measuring the amount of gravel left in a hollow tube 1 h after presentation to the rat, is reduced by peripheral nerve injury (tibial nerve transection (TNT), L5 spinal nerve transection (SNT) and partial sciatic nerve ligation (PSNL)) and also following inflammation induced by intra-plantar injection of Complete Freund's Adjuvant (CFA). Gabapentin (100 mg/kg sc) but not at 30 mg/kg sc significantly reduced burrowing activity in naive rats. ⋯ The level of mechanical hypersensitivity in rats with peripheral nerve injury did not correlate with the deficit in burrowing indicating that different parameters of the holistic pain experience are measured in these paradigms. Gabapentin at 30 mg/kg sc, but not 100 mg/kg sc, reversed the deficit in burrowing induced by TNT and ibuprofen (30 mg/kg sc) reversed the effect of CFA on burrowing. These experiments show that measurement of burrowing is a simple, objective assay of innate rodent behaviour affected by pain that is ethologically relevant to the rat, does not rely wholly on evoking a reflex and can dissociate a selective analgesic dose of gabapentin from one inducing motor impairment in the same animal.