These findings suggest that colonic luminal H(2)S/NaHS plays pronociceptive roles, and imply that the underlying mechanisms might involve sensitisation/activation of T-type channels probably in the primary afferents, aside from the issue of the selectivity of mibefradil.

Hydrogen sulfide (H(2)S) formed from l-cysteine by multiple enzymes including cystathionine-gamma-lyase (CSE) is now considered a gasotransmitter in the mammalian body. Our previous studies have shown that H(2)S activates/sensitizes Ca(v)3.2 T-type Ca(2+) channels, leading to facilitation of somatic and visceral nociception, and that CSE-derived endogenous H(2)S participates in inflammatory pain. Here, we show novel evidence for involvement of the endogenous H(2)S-Ca(v)3.2 pathway in neuropathic pain. In the rat subjected to the right L5 spinal nerve cutting (L5SNC), a neuropathic pain model, i.p. administration of dl-propargylglycine (PPG) and beta-cyanoalanine, irreversible and reversible CSE inhibitors, respectively, strongly suppressed the neuropathic hyperalgesia/allodynia. The anti-hyperalgesic effect of PPG was reversed by intraplantar administration of NaHS, a donor for H(2)S, in the L5SNC rat. Intraplantar administration or topical application of mibefradil, a T-type Ca(2+) channel blocker, reversed hyperalgesia in the L5SNC rat. The protein levels of Ca(v)3.2, but not CSE, in the ipsilateral L4, L5 and L6 dorsal root ganglia were dramatically upregulated in the L5SNC rat. Finally, silencing of Ca(v)3.2 in DRG by repeated intrathecal administration of Ca(v)3.2-targeting siRNA significantly attenuated the neuropathic hyperalgesia in the L5SNC rat. In conclusion, our data suggest that Ca(v)3.2 T-type Ca(2+) channels in sensory neurons are upregulated and activated/sensitized by CSE-derived endogenous H(2)S after spinal nerve injury, contributing to the maintenance of neuropathic pain. We thus propose that Ca(v)3.2 and CSE could be targets for the development of therapeutic drugs for the treatment of neuropathic pain.

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Twenty strains of Mycoplasma hyorhinis were investigated for their in vitro susceptibilities to 15 antimicrobial agents by broth and agar dilution methods. Two of the 20 field strains showed low susceptibility to 14- and 16-membered macrolide antimicrobial agents tested. The two field strains were considered inducibly resistant to macrolides.

The transport mechanism of the ring current ions differs among ion energies. Lower‐energy (≲150 keV) ions are well known to be transported convectively. Higher‐energy (≳150 keV) protons are reported to be transported diffusively, while there are few reports about transport of higher‐energy oxygen ions. We report the radial transport of higher‐energy oxygen ions into the deep inner magnetosphere during the late main phase of the magnetic storm on 23–25 April 2013 observed by the Van Allen Probes spacecraft. An enhancement of 1–100 mHz magnetic fluctuations is simultaneously observed. Observations of 3 and 30 mHz geomagnetic pulsations indicate the azimuthal mode number is ≤10. The fluctuations can resonate with the drift and bounce motions of the oxygen ions. The results suggest that the combination of the drift and drift‐bounce resonances is responsible for the radial transport of higher‐energy oxygen ions.

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