Pioglitazone attenuates tactile allodynia and microglial activation in mice with peripheral nerve injury

To test the possibility of a peroxisome proliferator activated receptor (PPAR) γ agonist to treat neuropathic pain, we examined the effects of pioglitazone, a PPARγ agonist, on tactile allodynia and expression of activated microglia in the dorsal horn of spinal cord using neuropathic pain model. The unilateral sciatic nerve was partially ligated (PSL) in male ICR mice. Pioglitazone (1-25 mg/kg p.o.) was administrated to mice once daily for five days immediately after PSL. We stimulated the footpad of the hind paw of mice using a von Frey filament to estimate tactile allodynia on day 5 of PSL. The activated microglia in the lumbar spinal cord was observed by immunohistochemistry with anti-Iba1 antibody, a marker for activated microglia. The number of Iba1-immunoreactive cells was counted in the dorsal horn spinal cord. On day 5, significant allodynia was developed in PSL mice. Pioglitazone significantly attenuated the tactile allodynia in a dose of 1-25 mg/kg. However, these doses of pioglitazone did not affect nociceptive responses in sham mice. Moreover, on day 6, the number of activated microglia was significantly increased in the ipsilateral dorsal horn of mice. The increase in the number of activated microglia induced by PSL was significantly suppressed by pioglitazone (1-25 mg/kg p.o.). Pioglitazone did not affect the number of activated microglia in sham mice. These results suggest that PPARγ activation inhibits the development of tactile allodynia and the expression of activated microglia in the dorsal horn of spinal cord in mice with PSLinduced peripheral nerve injury.