Analgesic effect of dimethyl trisulfide in mice is mediated by TRPA1 and sst4 receptors.

TRPA1 receptors are calcium-permeable ligand-gated channels expressed in primary sensory neurons and involved in inflammation and pain. Activation of these neurons might have analgesic effect. Suggested mechanism of analgesic effect mediated by TRPA1 activation is the release of somatostatin (SOM) and its action on sst4 receptors. In the present study analgesic effect of TRPA1 activation on primary sensory neurons by organic trisulfide compound dimethyl trisulfide (DMTS) presumably leading to SOM release was investigated. Opening of TRPA1 by DMTS in CHO cells was examined by patch-clamp and fluorescent Ca2+ detection. Ca2+ influx upon DMTS administration in trigeminal ganglion (TRG) neurons of TRPA1 receptor wild-type (WT) and knockout (KO) mice was detected by ratiometric Ca2+ imaging. SOM release from sensory nerves of murine skin was assessed by radioimmunoassay. Analgesic effect of DMTS in mild heat injury-induced mechanical hyperalgesia was examined by dynamic plantar aesthesiometry. Regulatory role of DMTS on deep body temperature (Tb) was measured by thermocouple thermometry with respirometry and by telemetric thermometry. DMTS produced TRPA1-mediated currents and elevated [Ca2+]i in CHO cells. Similar data were obtained in TRG neurons. DMTS released SOM from murine sensory neurons TRPA1-dependently. DMTS exerted analgesic effect mediated by TRPA1 and sst4 receptors. DMTS-evoked hypothermia and hypokinesis were attenuated in freely-moving TRPA1 KO animals. Our study has presented original evidence regarding analgesic action of DMTS which might be due to TRPA1-mediated SOM release from sensory neurons and activation of sst4 receptors. DMTS could be a novel analgesic drug candidate.

A comparison of the antimicrobial property of lidocaine/prilocaine cream (EMLA) and an alcohol-based disinfectant on intact human skin flora.

BACKGROUND: The application of EMLA cream is indicated for topical anesthesia of the skin in connection with IV cannulation. Recently, we described that EMLA cream has an antibacterial effect in vitro. METHODS: The impact of the local anesthetic lidocaine/prilocaine cream (EMLA) on intact human skin flora was compared to that of an alcohol-based skin disinfectant (Skinsept Pur). Samples were taken from 0 to 12 h after treatment. RESULTS: The number of colony forming units (cfu) on the skin decreased significantly after both EMLA and Skinsept Pur treatment from 44.9 +/- 1.3 (42.4 +/- 7.0) to 0.9 +/- 0.17 (1.61 +/- 0.47) cfu/cm(2), respectively (mean +/- sem), at the first sampling time (1 h) and remained significantly below 0 h values for the study period. The cfu count was significantly lower with EMLA cream at 4, 6, and 12 h compared to Skinsept Pur. CONCLUSION: EMLA cream has a longer bacteriostatic effect after early bactericidal impact compared to skin disinfection with Skinsept Pur.