Pain
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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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Chronic pain is a public health problem with high impact on various population segments. There are few population studies with the aim of delineating the profile of the chronic pain patient, and generating data for actions to prevent, control and minimize the problem. The aim of this study was to estimate the prevalence of chronic pain in the population of Salvador, Bahia, Brazil and identify independent predictors associated with this morbidity. ⋯ Among the studied factors, in the gross analysis, the following were shown to be associated with chronic pain: conjugal situation, smoking, excessive alcohol consumption, presence of central obesity and age, all with p<0.05. In the multivariate analysis, female sex, smoking, excessive alcohol consumption, and age were sustained as independent predictors. The presence of chronic pain was predominant in women, the elderly, smokers or ex-smokers and excessive alcohol consumers.
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The origins of chronic muscle pain development and maintenance are debated regarding the relative contributions of peripheral nociception and central pain processing. Bradykinin (BKN) and kallidin (KAL) have been suggested to be algesic kinins involved in muscle pain. This in vivo study investigates whether there were significant differences in interstitial muscle concentrations of BKN and KAL between chronic work-related trapezius myalgia (TM), chronic whiplash associated disorders (WAD), and healthy controls (CON). ⋯ In chronic pain, positive correlations existed between the two kinins and the difference in pain intensity between recovery and baseline. In this in vivo study of two groups of patients with chronic pain clinically involving the trapezius muscle, we found alterations - most prominent in TM - in the interstitial concentrations of BKN and KAL. The results indicated that the two kinins were involved in aspects of hyperalgesia.
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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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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.