BACKGROUND/AIMS: Interstitial cells of Cajal (ICC) and their special calcium-activated chloride channel, anoctamin-1 (ANO1) play pivotal roles in regulating colonic transit. This study is designed to investigate the role of ICC and the ANO1 channel in colonic transit disorder in dextran sodium sulfate (DSS)-treated colitis mice. METHODS: Colonic transit experiment, colonic migrating motor complexes (CMMCs), smooth muscle spontaneous contractile experiments, intracellular electrical recordings, western blotting analysis, and quantitative polymerase chain reaction were applied in this study. RESULTS: The mRNA and protein expressions of c-KIT and ANO1 channels were significantly decreased in the colons of DSS-colitis mice. The colonic artificial fecal-pellet transit experiment in vitro was significantly delayed in DSS-colitis mice. The CMMCs and smooth muscle spontaneous contractions were significantly decreased by 5-nitro-2-(3-phenylpropylamino)benzoic acid (NPPB), an ANO1 channel blocker, and NG-Nitro-L-arginine methyl ester hydrochloride (L-NAME), an inhibitor of nitric oxide synthase activity, in DSS-colitis mice compared with that of control mice. Intracellular electrical recordings showed that the amplitude of NPPB-induced hyperpolarization was more positive in DSS-colitis mice. The electric field stimulation-elicited nitric-dependent slow inhibitory junctional potentials were also more positive in DSS-colitis mice than those of control mice. CONCLUSION: The results suggest that colonic transit disorder is mediated via downregulation of the nitric oxide/ICC/ANO1 signalling pathway in DSS-colitis mice.
Animals ; Blotting, Western ; Chloride Channels ; Colitis ; Colon ; Dextrans ; Down-Regulation ; In Vitro Techniques ; Interstitial Cells of Cajal ; Mice ; Muscle, Smooth ; Myoelectric Complex, Migrating ; NG-Nitroarginine Methyl Ester ; Nitric Oxide Synthase ; Polymerase Chain Reaction ; RNA, Messenger ; Sodium

Objective To investigate the role of chemokine ligand 2 (CCL2) in the spinal cord expression in a rat model of tibia bone cancer pain.Methods Eighty-four female SD rats weighing 160-180 g were randomly divided into 3 groups ( n =28):control group (group C),sham operation group (group S) and tibia bone cancer pain group (group P).Tibia bone cancer pain was induced by intra-tibial inoculation of Walker-256 breast cancer cells.Paw withdral threshold to mechanical stimulation (MWT) was measured with von Frey filaments at 1 d before and at 1,3,7,10,14 and 21 d after inoculation.Six rats in each group were sacrificed after the measurement of MWT at 1 d before inoculation and at 7,14 and 21 d after inoculation.Lumbar 4-6 segments of the spinal cord were removed for determination of the expression of CCL2 by ELISA.The coexpression of CCL2 with Iba-1 (a specific marker of microglia),GFAP(a specific marker of astrocyte) and NeuN (a specific marker of neuron) was determined by double immunofluorescence assay after the measurement of MWT at 14 d after inoculation in group P.Results Compared with groups C and S,MWT was significantly decreased from 7 d to 21 d after inoculation,the expressive of CCI-2 in the spinal cord up-regulated at 7,14 and 21 d after inoculation in group P ( P ＜ 0.05).CCL2 was expressed in the microglia and astrocyte but not in neuron in the spinal cord dorsal horn in a rat model of tibia bone cancer pain.Conclusion Release of CCL2 from microglia and astrocytes in the spinal cord was involved in mechanical hyperalgesia in a rat model of tibia bone cancer pain.

Adult ; Age Factors ; Alcoholism ; complications ; China ; epidemiology ; Fatty Liver ; epidemiology ; etiology ; Female ; Humans ; Liver Diseases, Alcoholic ; epidemiology ; etiology ; Male ; Middle Aged ; Prevalence ; Sex Factors