Pain
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The objective of this study is to identify subgroups of patients with non-specific neck pain who are more likely to benefit from either physiotherapy, spinal manipulation therapy, or usual care, on the short- and long-term. Data of three recently finished randomised controlled trials, with similar design and setting, were combined. The combined study population consisted of 329 patients with non-specific neck pain in an adult (18-70years) primary care population in the Netherlands. ⋯ The analysis revealed three predictors for recovery of which the effect is modified by treatment: pain intensity (0-10 scale) in the short-term model, age and (no) accompanying low back pain in the long-term model. With these predictors a clinically relevant improvement in recovery rate (up to 25% improvement) can be established in patients receiving a tailored instead of a non-advised treatment. In conclusion we identified three characteristics that facilitate a deliberate treatment choice, to optimise benefit of treatment in patients with non-specific neck pain: age, pain intensity, and (no) accompanying low back pain.
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Comparative Study
The role of heterosynaptic facilitation in long-term potentiation (LTP) of human pain sensation.
Long-term potentiation (LTP) of nociceptive synaptic transmission induced by high-frequency electrical stimulation (HFS) predominantly modulates natural somatosensory perceptions mediated by Adelta- and Abeta-fibers in humans at the site of conditioning stimulation. The relative contribution of homo- and heterosynaptic mechanisms underlying those perceptual changes remained unclear. We therefore compared changes of the somatosensory profile between a conditioned skin site (homotopic zone) and an area adjacent to conditioning HFS (heterotopic zone). ⋯ Moreover, a small decrease of thresholds to blunt pressure was found at both zones (p<0.05). Pain summation (windup ratio), mechanical detection threshold as well as vibration detection threshold remained unchanged. Because none of the changes in sensory parameters was unique for the site of conditioning stimulation, these data suggest that heterosynaptic interactions are the predominant mechanism of LTP in nociceptive pathways.
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Palmitoylethanolamide (PEA) is an endogenous lipid that is thought to be involved in endogenous protective mechanisms activated as a result of stimulation of inflammatory response. In spite of the well demonstrated anti-inflammatory properties of PEA, its involvement in controlling pain pathways still remains poorly characterized. On this basis, we tested the efficacy of PEA in vivo against a peculiar persistent pain, such as neuropathic one. ⋯ The results indicated that CB(1), PPARgamma and TRPV1 receptors mediated the antinociception induced by PEA, suggesting that the most likely mechanism might be the so-called "entourage effect" due to the PEA-induced inhibition of the enzyme catalyzing the endocannabinoid anandamide (AEA) degradation that leads to an enhancement of its tissue levels thus increasing its analgesic action. In addition, the hypothesis that PEA might act through the modulation of local mast cells degranulation is sustained by our findings showing that PEA significantly reduced the production of many mediators such as TNFalpha and neurotrophic factors, like NGF. The findings presented here, in addition to prove the beneficial effects of PEA in chronic pain, identify new potential targets for analgesic medicine.
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Accumulating evidence points to significant cognitive disruption in individuals with Fibromyalgia Syndrome (FMS). This study was carried out in order to examine specific cognitive mechanisms involved in this disruption. Standardized experimental paradigms were used to examine attentional function and working memory capacity in 30 women with FMS and 30 matched controls. ⋯ These findings point to disrupted working memory as a specific mechanism that is disrupted in this population. The results of this study suggest that pain in FMS may play an important role in cognitive disruption. It is likely that many factors, including disrupted cognition, play a role in the reduced quality of life reported by individuals with FMS.
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The increasing complexity of randomized clinical trials and the practice of obtaining a wide variety of measurements from study participants have made the consideration of multiple endpoints a critically important issue in the design, analysis, and interpretation of clinical trials. Failure to consider important outcomes can limit the validity and utility of clinical trials; specifying multiple endpoints for the evaluation of treatment efficacy, however, can increase the rate of false positive conclusions about the efficacy of a treatment. ⋯ To decrease the probability of a Type I error (i.e., the likelihood of obtaining statistically significant results by chance) in pain clinical trials, the use of gatekeeping procedures and other methods that correct for multiple analyses is recommended when a single primary endpoint does not adequately reflect the overall benefits of treatment. We emphasize the importance of specifying in advance the outcomes and clinical decision rule that will serve as the basis for determining that a treatment is efficacious and the methods that will be used to control the overall Type I error rate.