ABSTRACT
Aim To investigate the effect of intrathecal injection of fluorocitrate(Fc)on mechanical and thermal hyperalgesia induced by complete Freund's adjuvant(CFA)injection in rats.Methods The mechanical withdrawal threshold(MWT)and thermal withdrawal latency(TWL)were measured before and after CFA or Fc treatment.The changes of glial fibrillary acidic protein(GFAP)and OX-42(a microglial marker)expression in the spinal cord dorsal horn were evaluated by immunohistochemistry analysis.Results Rats with CFA-induced arthritis showed mechanical allodynia and thermal hyperalgesia,which was correlated with the increased GFAP and OX-42 expression in the spinal cord dorsal horn.Intrathecal injection of Fc markedly suppressed CFA-induced thermal hyperalgesia and mechanical allodynia.Fc significantly attenuated the activation of GFAP and OX-42 in the spinal cord dorsal horn.Conclusions The glia activation in spinal cord is closely related to the progress of CFA-induced peripheral hyperalgesia.Fc may exert antihyperalgesic effect by inhibiting the activation of astrocyte and microglia.
ABSTRACT
Objective To evaluate the role of gliocytes in the spinal cord in the development of inflammatory pain (IP) in rats. Methods Adult male SD rats weighing 180-220 g were used in this experiment. A catheter was implanted in the subarachnoid space according to the method described by Yang. Animals with abnormal motor function of the hindlimb after intrathecal (IT) catheter implantation were excluded. IP was induced by subcutaneous (sc) injection of complete Freund's adjuvant (CFA) 50 μl at the lateral side of the ankle joint of the right hindpaw. Sixty-five rats were randomly divided into 5 groups ( n = 13 each): group I IP control normal saline (NS) 50μl was injected sc instead of CFA; group II IP; group IE PC (IT) + IP control fluorinated citric acid (FC, a gliocyte metabolism inhibitor) 1 nmol/10μl was injected IT at 15 min before NS 50 μl sc injection; group IV NS (IT) + IP and group V FC (IT) + IP. The mechanical paw withdrawal threshold (MWT) and thermal paw withdrawal latency (TWL) were measured 2 d before induction of IP (T_0, baseline) .before and at 2, 4, 6, 8, 10, 12, 24 and 26 h (T_(1-9)) after sc NS or CFA injection. Five enimals in each group were killed at T_5 (8 h after sc NS/CFA injection) and the lumbar segment (L_(4,5)) was removed for determination of glial fibrillary acidic protein ( CFAP) and OX-42 expression by immuno-histochemistry. Results In group Ⅱ and Ⅳ sc CFA significantly decreased MWT and TWL. Mechanical and thermal hyperalgegia induced by sc CFA was significantly suppressed by intrathecal FC in group V . IP significantly increased GFAP and OX-42 expression in the spinal cord. Intrathecal FC significantly attenuated IP-induced up-regulation of GFAP and OX-42 expression in the spinal cord. Conclusion The activation of gliocytes in the spinal cord is involved in the development of CFA-induced hyperalgesia in rats.
ABSTRACT
Objective To investigate the effect of propentofylline on nerve growth factor (NGF) and IL-1βrelease from rat cerebral cortical astrocytes. Methods Primary cultured rat astrocytes from SD rats (1-3 d,weighing 6-8 g) after 4 passages were randomly divided into 8 groups ( n = 6 wells each): group Ⅰ control (group C); group Ⅱ , Ⅲ, Ⅳ the astrocytes were exposed to propentofylline 10, 100 and 1000 μmol/L respectively (group P1, P2, P3 ); group Ⅴ the astrocytes were exposed to LPS 1 μg/ml and group Ⅵ, Ⅶ, Ⅷ the astrocytes were exposed to propentofylline 10, 100 and 1000 μmol/L in addition to LPS 1 μg/ml (group P1 + LPS, P2 + LPS,P3 + LPS). The astrocytes were then incubated for 3 days in all 8 groups. The concentrations of IL-1β and NGF in the supernatant were detected at 1 and 3 days of incubation using ELISA. Results LPS activated astrocytes resulting in decrease in NGF release and increase in IL-1β release. Propentofylline significantly increased NGF release and decreased IL-1β release from astrocytes incubated alone or with LPS by suppressing activation of astrocytes. Conclusion Propentofylline can enhance NGF release and inhibit IL-1β release from rat cerebral cortical astrocytes.