Pain
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Ultraviolet (UV) induced cutaneous inflammation is emerging as a model of pain with a novel sensory phenotype. A UVB dose of 1000mJ/cm2 produces a highly significant thermal and mechanical hypersensitivity. Here we examined the properties and mechanisms of such hyperalgesia in rats. ⋯ Notably alteration in mechanical responses of Adelta- and heat-insensitive C-nociceptors were particular to stronger stimuli. Spontaneous activity was not induced by this dose of UVB. We conclude that UVB-induced mechanical hyperalgesia may be explained by a net shift in peripheral nociceptor response properties.
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We tested whether it is possible to selectively block pain signals in the orofacial area by delivering the permanently charged lidocaine derivative QX-314 into nociceptors via TPRV1 channels. We examined the effects of co-applied QX-314 and capsaicin on nociceptive, proprioceptive, and motor function in the rat trigeminal system. QX-314 alone failed to block voltage-gated sodium channel currents (I(Na)) and action potentials (APs) in trigeminal ganglion (TG) neurons. ⋯ Co-application of QX-314 and capsaicin inhibited the jaw-opening reflex evoked by noxious electrical stimulation of the tooth pulp when applied to a sensory but not a motor nerve, and produced long-lasting analgesia in the orofacial area. These data show that selective block of pain signals can be achieved by co-application of QX-314 with TRPV1 agonists. This approach has potential utility in the trigeminal system for treating dental and facial pain.
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Recent studies have demonstrated significant changes in the neuronal ganglioside status associated with altered functional states of nociceptive primary sensory neurons. In the present study, therefore, the effects of the inhibition of glucosylceramide synthase, the key enzyme of ganglioside synthesis, were studied on chemically defined populations and on the activation of TRPV1 of cultured adult rat sensory ganglion neurons. In control cultures, capsaicin resulted in the activation of TRPV1 in 29.7+/-2.5% of the neurons, as assessed with the cobalt uptake assay. ⋯ The proportions of IB4- and CGRP-positive neurons were not significantly affected by d-PDMP. The present observations demonstrate that inhibition of neuronal ganglioside synthesis profoundly modulates the expression of the TRPV1 receptor, apparently leaving other markers of nociceptive neurons, such as CGRP and IB4, unaffected. The findings indicate that as yet unidentified ganglioside(s) synthesized by the glucosylceramide synthase pathway may be essential for nociception through mechanisms which may implicate membrane lipid raft function and/or altered nerve growth factor signaling, which are essential for the TRPV1 receptor function.
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Knowledge of the position of one's limbs is an essential component of daily function and relies on complex interactions of sensorimotor body schema-related information. Those with Complex Regional Pain Syndrome (CRPS) express difficulty in knowing where their affected limb is positioned. The aim of this study was to determine the degree to which experimental data supported the reported difficulty in limb position sense. ⋯ Evidence of bilateral arm positioning impairments in unilateral arm CRPS suggests that central mechanisms are involved. Cortical reorganisation in regions associated with the body schema (i.e. primary somatosensory and parietal cortices) is proposed as an explanation. The exact relationship between pain and limb position deficits requires further exploration.