Figure 3.

Delayed activation of microglia is involved in the maintenance, but not the induction, of bone cancer pain. A, B, Development of mechanical allodynia (A) and thermal hyperalgesia (B) is blocked by repeated intrathecal injections of astrocyte metabolic inhibitor fluorocitrate (FC; 0.8 μg = 1 nmol) but not by microglia inhibitor minocycline (Mino; 100 μg) during the early phase of bone cancer pain. FC or Mino is given once daily for 6 d with the first injection occurring 30 min before intratibia inoculation. **p < 0.01 versus baseline. ##p < 0.01 versus vehicle (Veh)- and Mino-treated groups. C, Repeated intrathecal injections of FC (0.8 μg = 1 nmol, once daily for 6 d) do not influence motor coordination in normal rats in a rotarod test. D, Few fluorescein-labeled apoptotic nuclei were detected in the lumbar spinal dorsal horns from normal or bone cancer rats with repeated intrathecal injections of FC (0.8 μg = 1 nmol, once daily for 6 d). HL-60 cells treated by 0.5 μg/ml actinomycin D for 19 h to induce apoptosis were used as a positive control. E, F, Intrathecal injection of either FC or Mino on PTD 14 significantly reduces bone cancer-induced mechanical allodynia (E) and thermal hyperalgesia (F). *p < 0.05; **p < 0.01 versus vehicle controls.