Pain
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Comparative Study
Spatiotemporal and anatomical analyses of P2X receptor-mediated neuronal and glial processing of sensory signals in the rat dorsal horn.
Extracellularly released adenosine triphosphate (ATP) modulates sensory signaling in the spinal cord. We analyzed the spatiotemporal profiles of P2X receptor-mediated neuronal and glial processing of sensory signals and the distribution of P2X receptor subunits in the rat dorsal horn. Voltage imaging of spinal cord slices revealed that extracellularly applied ATP (5-500 μM), which was degraded to adenosine and acting on P1 receptors, inhibited depolarizing signals and that it also enhanced long-lasting slow depolarization, which was potentiated after ATP was washed out. ⋯ Astrocytes expressed the P2X(7) subunit. These findings indicate that extracellular ATP is degraded into adenosine and prevents overexcitation of the sensory system, and that ATP acts on pre- and partly on postsynaptic neuronal P2X receptors and enhances synaptic transmission, predominantly in the deep layer. Astrocytes are involved in sensitization of sensory network activity more importantly in the superficial than in the deep layer.
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Comparative Study
Keratinocyte expression of calcitonin gene-related peptide β: implications for neuropathic and inflammatory pain mechanisms.
Calcitonin gene-related peptide (CGRP) is a vasodilatory peptide that has been detected at high levels in the skin, blood, and cerebrospinal fluid (CSF) under a variety of inflammatory and chronic pain conditions, presumably derived from peptidergic C and Aδ innervation. Herein, CGRP immunolabeling (IL) was detected in epidermal keratinocytes at levels that were especially high and widespread in the skin of humans from locations afflicted with postherpetic neuralgia (PHN) and complex region pain syndrome type 1 (CRPS), of monkeys infected with simian immunodeficiency virus, and of rats subjected to L5/L6 spinal nerve ligation, sciatic nerve chronic constriction, and subcutaneous injection of complete Freund's adjuvant. Increased CGRP-IL was also detected in epidermal keratinocytes of transgenic mice with keratin-14 promoter driven overexpression of noggin, an antagonist to BMP-4 signaling. ⋯ Cutaneous peptidergic innervation has been shown to express predominantly the alpha isoform of CGRP. Keratinocytes also express the cognate CGRP receptor components, Calcitonin receptor-like receptor (CRLR), Receptor activity-modifying protein 1 (RAMP1), CGRP-receptor component protein (RCP) consistent with known observations that CGRP promotes several functional changes in keratinocytes, including proliferation and cytokine production. Our results indicate that keratinocyte-derived CGRPβ may modulate epidermal homeostasis through autocrine/paracrine signaling and may contribute to chronic pain under pathological conditions.
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Comparative Study
Nerve growth factor selectively decreases activity-dependent conduction slowing in mechano-insensitive C-nociceptors.
Nerve growth factor (NGF) induces acute sensitization of nociceptive sensory endings and long-lasting hyperalgesia. NGF modulation of sodium channel expression might contribute to neurotrophin-induced hyperalgesia. Here, we investigated NGF-evoked changes of the activity-dependent slowing of conduction in porcine C-fibers. ⋯ Accordingly, the number of fibers with pronounced ADS decreased but more units with pronounced ADS were mechano-sensitive. Spontaneously active C-fibers were increased above the control level (1%) by NGF 8 μg (8%). The results demonstrate that NGF changes the functional axonal characteristics of mechano-insensitive C-fibers and enhances spontaneous activity thereby possibly contributing to hyperalgesia.
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Randomized Controlled Trial Comparative Study
The effects of total and REM sleep deprivation on laser-evoked potential threshold and pain perception.
We investigated the effects of total and rapid eye movement (REM) sleep deprivation on the thermal nociceptive threshold and pain perception using the objective laser-evoked potential (LEP) and the subjective visual analogue scale (VAS). Twenty-eight male adult volunteers were assigned into Control (CTRL), Total (T-SD), and REM (REM-SD) Sleep Deprivation groups. The T-SD and REM-SD volunteers were totally or selectively deprived of sleep for 2 and 4 consecutive nights, respectively. ⋯ No significant variations were observed in the REM-SD group, suggesting a predominant role for slow wave sleep rather than selective REM-SD in pain perception. Also, for both sleep-deprived groups, the mean values of the LEP threshold and VAS ratings showed a gradual increase that was proportional to the SD deprivation time, followed by a decrease after 1 night of sleep restoration. These findings demonstrate a hyperalgesic modification to pain perception (as reflected by the augmented VAS) and a concomitant increase in the LEP threshold following T-SD, an apparently contradictory effect that can be explained by differences in the ways that attention affects these pain measurements.