Pain
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It is increasingly recognized that pain-induced plasticity may not only provoke sensory gain (hyperalgesia), but also sensory decline, i.e. hypoesthesia and hypoalgesia. We investigated perceptual changes by conditioning electrical stimulation of peptidergic C-nociceptors differing in stimulation frequencies and duty cycles at the left forearm. Four noxious electrical stimulation paradigms (Stim1: 0.5 Hz, continuously; Stim2: 20 Hz, continuously; Stim3: 1s 20 Hz train, 1s break; Stim4: 1s 20 Hz train, 2s break) were applied. ⋯ In summary, we describe here that depending on the applied frequencies and duty cycles, either sensory gain (i.e. hyperalgesia) or sensory decline (i.e. hypoesthesia and hypoalgesia) can be induced. Sensory decline was found to be centrally mediated. Underlying mechanisms may include differential recruitment of inhibitory and facilitating gain control systems leading to homo- and heterosynaptic inhibition or facilitation at the level of the spinal cord or interference of noxious input with tactile processing in the cortex.
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Comparative Study
Prevalence and characteristics of opioid use in the US adult population.
This report describes the prevalence of opioid use in the US adult population, overall and in subgroups, the characteristics of opioid use, and concomitant medication use among opioid users. Data were obtained from the Slone Survey, a population-based random-digit dialing survey. One household member was randomly selected to answer a series of questions regarding all medications taken during the previous week. ⋯ Regular opioid users were more likely to use stool softeners/laxatives (9% vs. 2%), proton pump inhibitors (25% vs. 8%), and antidepressants (35% vs. 10%). From this nationally-representative telephone survey, we estimate that over 4.3 million US adults are taking opioids regularly in any given week. Information on the prevalence and characteristics of use is important as opioids are one of the most widely prescribed classes of drugs in the US.
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Comparative Study
A-kinase anchoring protein mediates TRPV1 thermal hyperalgesia through PKA phosphorylation of TRPV1.
Certain phosphorylation events are tightly controlled by scaffolding proteins such as A-kinase anchoring protein (AKAP). On nociceptive terminals, phosphorylation of transient receptor potential channel type 1 (TRPV1) results in the sensitization to many different stimuli, contributing to the development of hyperalgesia. In this study, we investigated the functional involvement of AKAP150 in mediating sensitization of TRPV1, and found that AKAP150 is co-expressed in trigeminal ganglia (TG) neurons from rat and associates with TRPV1. ⋯ In CHO cells, the PKA RII binding site on AKAP was necessary for PKA enhancement of TRPV1-mediated Ca2+-accumulation. In addition, AKAP150 knock-down in cultured TG neurons attenuated PKA sensitization of TRPV1 activity and in vivo administration of an AKAP antagonist significantly reduced prostaglandin E2 sensitization to thermal stimuli. These data suggest that AKAP150 functionally regulates PKA-mediated phosphorylation/sensitization of the TRPV1 receptor.