Pain
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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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Comparative Study
Fast non-genomic effects of progesterone-derived neurosteroids on nociceptive thresholds and pain symptoms.
Fast Inhibitory controls mediated by glycine (GlyRs) and GABAA receptors (GABAARs) play an important role to prevent the apparition of pathological pain symptoms of allodynia and hyperalgesia. The use of positive allosteric modulators of these receptors, specifically expressed in the spinal cord, may represent an interesting strategy to limit or block pain expression. In this study, we have used stereoisomers of progesterone metabolites, acting only via non-genomic effects, in order to evaluate the contribution of GlyRs and GABAARs for the reduction of mechanical and thermal heat hypernociception. ⋯ We clearly show that 3alpha5beta neurosteroid exerts an antinociceptive effect via a positive allosteric modulation of GABAARs but, at the same time, is pronociceptive by reducing GlyR function. This illustrates the importance of the inhibitory amino acid receptor channels and their allosteric modulators in spinal pain processing. Moreover, our results indicate that neurosteroids, which are synthesized in the dorsal horn of the spinal cord and have limited side effects, may be of significant interest in order to treat pathological pain symptoms.
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The standard rodent model of itch uses scratching with the hind limb as a behavioral response to pruritic stimuli applied to the nape of the neck. The assumption is that scratching is an indicator of the sensation of itch. But because only one type of site-directed behavior is available, one cannot be certain that scratching is not a response to nociceptive or other qualities of sensations in addition to, or instead of, itch. ⋯ In contrast, when the same chemicals were injected into the cheek of the mouse, there were two site-directed behaviors: histamine again elicited scratching with the hind limb, but capsaicin evoked wiping with the forelimb. We conclude that the "cheek model of itch" in the mouse provides a behavioral differentiation of chemicals that elicit predominantly itch in humans from those that evoke nociceptive sensations. That is, the model provides a behavioral differentiation between itch and pain in the mouse.
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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.
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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.