Figure 4.
The different effect of glial inhibitors (propentofylline, fluorocitrate, and minocycline) on behavioral hyperalgesia/allodynia at early (3 d) and later (14 d) time points after CCI-ION. At posttreatment, the glial inhibitor propentofylline (A), the selective astrocytic inhibitor fluorocitrate (B), and the microglial inhibitor minocycline (C) are microinjected into the RVM at 3 d (right column) and 14 d (left column) after sham operation or CCI-ION. The dose-dependent effects of the glial inhibitors on behavioral hyperalgesia/allodynia are measured at 14 d after the surgery. An effective high dose of the inhibitor is then used for behavioral observation at the 3 d time point. Vehicles are microinjected as a control. A, PPF (1 fmol, 100 fmol, and 10 pmol) produces a dose-dependent attenuation of CCI-induced mechanical hyperalgesia and allodynia at 14 d, persistent for 4–24 h compared with vehicle microinjection in CCI rats (left). High-dose propentofylline (10 pmol) has no effect on EF50 values at 14 d in sham rats (left). This dose of propentofylline transiently blocks moderate hyperalgesia and allodynia at 3 d compared with vehicle in sham-operated rats (right), and also significantly abolishes mechanical allodynia at 3 d after CCI compared with vehicle in CCI rats (right). B, Two doses of FC (1 and 100 fmol) after microinjection into the RVM significantly attenuate hyperalgesia and allodynia similarly at least for 6 h, compared with vehicle treatment at 14 d in CCI rats (left). High dose of fluorocitrate (100 fmol) has no effect on EF50 values at 14 d in sham rats (left). However, fluorocitrate (100 fmol) does not prevent CCI-induced behavioral hypersensitivity to mechanical stimulation at 3 d after CCI or sham operation (right). C, In contrast, microinjection of MC (1 pmol) into the RVM significantly reduces hyperalgesia and allodynia for 6 h at 3 d after CCI-ION compared with vehicle treatment in CCI rats, and also transiently blocks sham operation-induced mechanical hypersensitivity (right). Lower dose of minocycline (10 fmol) induced a slight and short-lasting inhibition for CCI-induced allodynia (right). The two doses of minocycline have no effect on CCI-induced hyperalgesia and allodynia at 14 d (left). Also, there are no changes in EF50 values after minocycline (1 pmol) injection at 14 d after sham-operated rats. ***, ###p < 0.001; **p < 0.01; *, #,^ p < 0.05 versus CCI plus vehicle in left. ***p < 0.001, *p < 0.05, CCI plus drug versus CCI plus vehicle in right. #p < 0.05, sham plus drug versus sham plus vehicle in right. Error bars indicate SEM.
