Aberrant mechanosensation has an important role in different pain states. Here we show that Epac1 (cyclic AMP sensor) potentiation of Piezo2-mediated mechanotransduction contributes to mechanical allodynia. Dorsal root ganglia Epac1 mRNA levels increase during neuropathic pain, and nerve damage-induced allodynia is reduced in Epac1−/− mice. The Epac-selective cAMP analogue 8-pCPT sensitizes mechanically evoked currents in sensory neurons. Human Piezo2 produces large mechanically gated currents that are enhanced by the activation of the cAMP-sensor Epac1 or cytosolic calcium but are unaffected by protein kinase C or protein kinase A and depend on the integrity of the cytoskeleton. In vivo, 8-pCPT induces long-lasting allodynia that is prevented by the knockdown of Epac1 and attenuated by mouse Piezo2 knockdown. Piezo2 knockdown also enhanced thresholds for light touch. Finally, 8-pCPT sensitizes responses to innocuous mechanical stimuli without changing the electrical excitability of sensory fibres. These data indicate that the Epac1–Piezo2 axis has a role in the development of mechanical allodynia during neuropathic pain.

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Objective To compare the eÃcacy and safety of a fixed Q max or >20% decrease in total IPSS. Adverse reactions possibly or probably related to study medication dose (0.2 mg) of tamsulosin, a selective a 1 A-adrenoreceptor antagonist, with an increasing dose (1-5 mg) were recorded throughout the treatment period.

Parasitological examination of samples from tombs of the Korean Joseon Dynasty (1392-1910) could be helpful to researchers in understanding parasitic infection prevalence in pre-industrial Korean society. Whereas most of our previous parasitological studies revealed the presence of ancient parasite eggs in coprolites of Korean mummies, a sample from a man living in late 17th century Korea proved to be relatively unique in possessing what appeared to be several species of parasite larvae. The larvae identified included Strongyloides stercoralis and Trichostrongylus spp., along with eggs of Ascaris lumbricoides, Trichuris trichiura, and Paragonimus westermani. Since ancient parasite larvae retain enough morphology to make proper species identification possible, even after long burial times, the examination of parasite larvae within ancient samples will be conducted more carefully in our future work.