Plos One
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Transient receptor potential channels are important mediators of thermal and mechanical stimuli and play an important role in neuropathic pain. The contribution of hereditary variants in the genes of transient receptor potential channels to neuropathic pain is unknown. We investigated the frequency of transient receptor potential ankyrin 1, transient receptor potential melastin 8 and transient receptor potential vanilloid 1 single nucleotide polymorphisms and their impact on somatosensory abnormalities in neuropathic pain patients. ⋯ Two main subgroups characterized by preserved (1) and impaired (2) sensory function were identified. In subgroup 1 transient receptor potential vanilloid 1 1911A>G led to significantly less heat hyperalgesia, pinprick hyperalgesia and mechanical hypaesthesia (p = 0.006, p = 0.005 and p<0.001) and transient receptor potential vanilloid 1 1103C>G (rs222747, M315I) to cold hypaesthesia (p = 0.002), but there was absence of associations in subgroup 2. In this study we found no evidence that genetic variants of transient receptor potential channels are involved in the expression of neuropathic pain, but transient receptor potential channel polymorphisms contributed significantly to the somatosensory abnormalities of neuropathic pain patients.
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Itch, or pruritus, is an important clinical problem whose molecular basis has yet to be understood. Recent work has begun to identify genes that contribute to detecting itch at the molecular level. ⋯ Pirt contributes to both histaminergic and nonhistaminergic itch and, crucially, is involved in forms of itch that are both TRPV1-dependent and -independent. Our findings demonstrate that the function of Pirt extends beyond nociception via TRPV1 regulation to its role as a critical component in several itch signaling pathways.
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K(V)7/KCNQ channels are widely expressed in neurons and they have multiple important functions, including control of excitability, spike afterpotentials, adaptation, and theta resonance. Mutations in KCNQ genes have been demonstrated to associate with human neurological pathologies. However, little is known about whether K(V)7/KCNQ channels are expressed in oligodendrocyte lineage cells (OLCs) and what their functions in OLCs. ⋯ These findings showed that K(V)7/KCNQ channels were functionally expressed in rat primary cultured OLCs and might play an important role in OPCs functioning in physiological or pathological conditions.
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In the management of clinical low back pain (LBP), actual damage to lower back areas such as muscles, intervertebral discs etc. are normally targeted for therapy. However, LBP may involve not only sensory pain, but also underlying affective pain which may also play an important role overall in painful events. Therefore we hypothesized that visualization of a painful event may trigger painful memories, thus provoking the affective dimension of pain. ⋯ All subjects with LBP reported experiencing discomfort and 7 LBP subjects reported experiencing pain. In contrast to subjects without LBP, subjects with LBP displayed activation of the cortical area related to pain and emotions: the insula, supplementary motor area, premotor area, thalamus, pulvinar, posterior cingulate cortex, hippocampus, fusiform, gyrus, and cerebellum. These results suggest that the virtual LBP stimuli caused memory retrieval of unpleasant experiences and therefore may be associated with prolonged chronic LBP conditions.
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GPR55 was recently identified as a putative receptor for certain cannabinoids, and lysophosphatidylinositol (LPI). Recently, the role of cannabinoids as GPR55 agonists has been disputed by a number of reports, in part, because studies investigating GPR55 often utilized overexpression systems, such as the GPR55-overexpressing HEK293 cells, which make it difficult to deduce the physiological role of endogenous GPR55. In the present study, we found that PC12 cells, a neural model cell line, express endogenous GPR55, and by using these cells, we were able to examine the role of endogenous GPR55. ⋯ This LPI-induced neurite retraction was found to be G(q)-independent and G(13)-dependent. Furthermore, inactivation of RhoA function via C3 toxin and GPR55 siRNA knockdown prevented LPI-induced neurite retraction. These results suggest that LPI, and not cannabinoids, causes neurite retraction in differentiated PC12 cells via a GPR55, G(13) and RhoA signaling pathway.