Pain
-
EphBs receptors and ephrinBs ligands are present in the adult brain and peripheral tissue and play a critical role in modulating multiple aspects of physiology and pathophysiology. Ours and other studies have demonstrated that spinal ephrinBs/EphBs signaling was involved in the modulation of nociceptive information and central sensitization. However, the role of ephrinBs/EphBs signaling in peripheral sensitization is poorly understood. ⋯ EphrinB1-Fc-induced hyperalgesia is accompanied with the NMDA receptor-mediated increase of expression in peripheral and spinal phosphorylated mitogen-activated protein kinases (phospho-MAPKs) including p-p38, pERK and pJNK, and also is prevented or reversed by the inhibition of peripheral and spinal MAPKs. Furthermore, in formalin inflammation pain model, pre-inhibition of EphBs receptors by the injection of EphB1-Fc reduces pain behavior, which is accompanied by the decreased expression of peripheral p-p38, pERK and pJNK. These data provide evidence that ephrinBs may act as a prominent contributor to peripheral sensitization, and demonstrate that activation of peripheral ephrinBs/EphBs system induces hyperalgesia through a MAPKs-mediated mechanism.
-
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.
-
Randomized Controlled Trial Comparative Study
Effects of morphine on the experimental illusion of pain produced by a thermal grill.
We compared the effects of systemic morphine on normal (heat and cold) pain and paradoxical burning pain evoked by the simultaneous application of innocuous warm and cold stimuli to the skin. Twelve healthy volunteers participated in a randomised, double-blind, cross-over study to compare the effects of intravenous administration of morphine (0.025 or 0.1mg/kg) or placebo (saline). Stimuli were applied to the palm of the right hand with a thermode ("thermal grill") composed of six bars, whose temperatures were controlled by Peltier elements. ⋯ No differences were observed for non-painful thermal sensations. The paradoxical burning pain evoked by a thermal grill can be modified pharmacologically by analgesics and share some mechanisms with normal pain. This unique experimental "illusion of pain" may represent a new model to test analgesics in healthy volunteers.
-
The objective of this study was to examine the influence of variations in contextual features of a physically demanding lifting task on the judgments of others' pain. Healthy undergraduates (n=98) were asked to estimate the pain experience of chronic pain patients who were filmed while lifting canisters at different distances from their body. Of interest was whether contextual information (i.e., lifting posture) contributed to pain estimates beyond the variance accounted for by pain behavior. ⋯ Results also indicated that observers' level of catastrophizing was associated with more accurate pain estimates. The results of a regression analysis further showed that observers' level of catastrophizing contributed to the prediction of the accuracy of pain estimates over and above the variance accounted for by the utilisation of contextual features. Discussion addresses the processes that might underlie the utilisation of contextual features of a pain-eliciting task when estimating others' pain.
-
Previously, we demonstrated that placebo analgesia (PA) accompanies reductions in neural activity during painful stimulation. This study investigated areas of the brain where the neural activity was increased during PA. The literature has associated PA with two potential mechanisms of action; one sustained (e.g., engaged for the duration of PA), the other, transitory (e.g., a feedback mechanism). ⋯ Conversely, brain regions with transient activity included linguistic centers in the left hemisphere and frontal regions of the right hemisphere generally associated with executive functioning. Together, these mechanisms likely engage analgesic processes and then simply monitor the system for unexpected stimuli, effectively liberating resources for other processes. Identifying brain regions associated with pain-modulation with different temporal profiles is consistent with the multidimensionality of PA and highlights the need for continued investigation of this construct.