The Antinociceptive Effect Of Intrathecal Administration Of Fluorocitrate In Rats With Arthritis

Part one:Pretreated administration of fluorocitrate affecting rat arthiritis hyperalgesiaObjective To investigate the effect of intrathecally(i.t.)administration of fluorocitrate(Fc)on the changes of mechanical and thermal hyperalgesia in rats with CFA-induced arthritis and evaluate the role of the spinal dorsal horn glia in hyperalgesia. Methods Adult male SD rats weighing 180-220g were used.The experiment was performed in two parts.In part one 40 adult male SD rats were randomly divided into 5 groups(n=8 each group):in groupⅠ,normal rats received normal saline(NS) subcutaneously(s.c.),in groupⅡ,normal rats received CFA s.c.,in groupⅢ,normal rats received Fc i.t.before NS s.c.,in groupⅣ,normal rats received NS i.t.before CFA s.c.,in groupⅤ,normal rats received Fc i.t.before CFA s.c.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)was measured before and at 2,4,6,8,10,12,24 and 26h after s.c..In part two,25 SD rats were randomly divided into 5 groups(n=5 each group):Five rats in groupⅠwere used as the blank control.All animals were killed after s.c.8h randomly.The change of glial fibrillary acidic protein(GFAP)and OX-42(an antibody recognizing the microglial marker complement receptor-3)expression in L4/5 segments of spinal cord was accessed by immunohistochemistry analysis.Results Fluorocitrate(1nmol in 10μl i.t.)solely had no effect on the TWL and MWT of normal rats.But it markedly suppressed CFA-induced thermal hyperalgesia and mechanical allodynia.Glia activation marker GFAP and OX-42 were deeply stained in spinal cord dorsal horn in group CFA.Fc i.t.significantly attenuated the activation of GFAP and OX-42 in the spinal cord dorsal horn in groupⅤ(P＜0.01).Conclusion The result suggests that Fc may have antihyperalgesia properties.The glia activation in spinal cord is closely related to the progress of CFA-induced peripheral hyperalgesia.Part two:The antinociceptive effect of intrathecal administration of fluorocitrate in inflammatory ratsObjective To investigate the antinociceptive effect of intrathecally(i.t.) administration of fluorocitrate(Fc)on the changes of mechanical and thermal hyperalgesia in a rat model of CFA-induced peripheral inflammation and evaluate the role played by the glia in spinal cord dorsal horn in hyperalgesia.Methods Adult male SD rats weighing 180-220g were used.The experiment was performed in two parts.In part one 40 adult male SD rats were randomly divided into 5 groups(n=8 each group): in groupⅠ,normal rats received normal saline(NS)subcutaneously(s.c.),in groupⅡ,normal rats received CFA s.c.,in groupⅢ,rats received Fc i.t.after NS s.c.24 h,in groupⅣ,rats received NS i.t.after CFA s.c.24 h,in groupⅤ,rats received Fc i.t.after CFA s.c.24 h.The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)was measured before and after drug i.t.per 2 h.In part two,25 SD rats were randomly divided into 5 groups(n=5 each group):Five rats in groupⅠwere used as the blank control.All animals were killed after drug i.t.6h randomly.The change of glial fibrillary acidic protein(GFAP)and OX-42(an antibody recognizing the microglial marker complement receptor-3)expression in L4/5 segments of spinal cord was accessed by immunohistochemistry analysis.Results Fluorocitrate(1nmol in 10μl i.t.)solely had no effect on the TWL and MWT of normal rats.But it markedly suppressed CFA-induced thermal hyperalgesia and mechanical allodynia.Glia activation marker GFAP and OX-42 were deeply stained in spinal cord dorsal horn in group CFA.Fc i.t.significantly attenuated the activation of GFAP and OX-42 in the spinal cord dorsal horn in groupⅤ(P＜0.01).Conclusion The result suggests that Fc may have antihyperalgesia properties.The glia activation in spinal cord is closely related to the progress of CFA-induced peripheral hyperalgesia.