Articles: itch.
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The Journal of physiology · Apr 2017
Lysophosphatidic acid-induced itch is mediated by signalling of LPA5 receptor, phospholipase D and TRPA1/TRPV1.
Lysophosphatidic acid (LPA) is an itch mediator, but not a pain mediator by a cheek injection model. Dorsal root ganglion neurons directly respond to LPA depending on transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1). LPA-induced itch-related behaviours are decreased in TRPA1-knockout (KO), TRPV1KO or TRPA1TRPV1 double KO mice. TRPA1 and TRPV1 channels are activated by intracellular LPA, but not by extracellular LPA following LPA5 receptor activation with an activity of Ca2+ -independent phospholipase A2 and phospholipase D. Intracellular LPA interaction sites of TRPA1 are KK672-673 and KR977-978 (K: lysine, R: arginine). ⋯ Intractable and continuous itch sensations often accompany diseases such as atopic dermatitis, neurogenic lesions, uremia and cholestasis. Lysophosphatidic acid (LPA) is an itch mediator found in cholestatic itch patients and it induces acute itch and pain in experimental rodent models. However, the molecular mechanism by which LPA activates peripheral sensory neurons remains unknown. In this study, we used a cheek injection method in mice to reveal that LPA induced itch-related behaviours but not pain-related behaviours. The LPA-induced itch behaviour and cellular effects were dependent on transient receptor potential ankyrin 1 (TRPA1) and vanilloid 1 (TRPV1), which are important for itch signal transduction. We also found that, among the six LPA receptors, the LPA5 receptor had the greatest involvement in itching. Furthermore, we demonstrated that phospholipase D (PLD) plays a critical role downstream of LPA5 and that LPA directly and intracellularly activates TRPA1 and TRPV1. These results suggest a unique mechanism by which cytoplasmic LPA produced de novo could activate TRPA1 and TRPV1. We conclude that LPA-induced itch is mediated by LPA5 , PLD, TRPA1 and TRPV1 signalling, and thus targeting TRPA1, TRPV1 or PLD could be effective for cholestatic itch interventions.
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Coding of itch versus pain has been heatedly debated for decades. However, the current coding theories (labeled line, intensity, and selectivity theory) cannot accommodate all experimental observations. Here we identified a subset of spinal interneurons, labeled by gastrin-releasing peptide (Grp), that receive direct synaptic input from both pain and itch primary sensory neurons. ⋯ Accordingly, we propose a "leaky gate" model in which Grp+ neurons transmit both itch and weak pain signals; however, upon strong painful stimuli, the recruitment of endogenous opioids works to close this gate, reducing overwhelming pain generated by parallel pathways. Consistent with our model, loss of these Grp+ neurons increased pain responses while itch was decreased. Our new model serves as an example of non-monotonic coding in the spinal cord and better explains observations in human psychophysical studies.
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The prevalence of cutaneous adverse food reactions (CAFRs) in dogs and cats is not precisely known. This imprecision is likely due to the various populations that had been studied. Our objectives were to systematically review the literature to determine the prevalence of CAFRs among dogs and cats with pruritus and skin diseases. ⋯ Among dogs and cats with pruritus and those suspected of allergic skin disease, the prevalence of CAFR is high enough to justify this syndrome to be ruled-out with a restriction (elimination)-provocation dietary trial. This must especially be considered in companion animals with nonseasonal pruritus or signs of allergic dermatitis.
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The spinal dorsal horn receives input from primary afferent axons, which terminate in a modality-specific fashion in different laminae. The incoming somatosensory information is processed through complex synaptic circuits involving excitatory and inhibitory interneurons, before being transmitted to the brain via projection neurons for conscious perception. ⋯ However, at present, we have only a limited understanding of the neuronal circuitry within this region, and this is largely because of the difficulty in defining functional populations among the excitatory and inhibitory interneurons. The recent discovery of specific neurochemically defined interneuron populations, together with the development of molecular genetic techniques for altering neuronal function in vivo, are resulting in a dramatic improvement in our understanding of somatosensory processing at the spinal level.
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Chronic itch (CI) is a common symptom in haemodialysis (HD) patients affecting about every 4th HD patient. Though it is known that health-related quality of life (HRQOL) is impaired in HD patients, data are lacking on how CI influences HRQOL in this group of patients, also regarding sex differences and the role of sleep and pain. ⋯ Impairments in HRQOL are a serious problem in HD patients. CI means an additional burden in affected patients, also impairing their HRQOL. GEHIS showed significant sex differences in HRQOL outcomes also in HD patients. CI and pain as well as sleep frequently occur combined and significantly impair HRQOL in HD patients. The care of HD patients should be complemented by psychosocial support and mental health services.