Involvement of protein isoprenylation in neuropathic pain induced by sciatic nerve injury in mice.

Isoprenylation is crucial step for activating many intracellular signaling. The present study examined whether inhibition of the protein isoprenylation could affect neuropathic pain in partial sciatic nerve-ligated mice. Intrathecal treatment with a geranylgeranyl transferase I inhibitor GGTI-2133, but not with a farnesyl transferase inhibitor FTI-277, dose-dependently blocked the thermal hyperalgesia in partial sciatic nerve-ligated mice. Intrathecal treatment with GGTI-2133 also attenuated the mechanical allodynia in partial sciatic nerve-ligated mice. Phosphorylated MARCKS expression was increased in the ipsilateral side of the spinal cord dorsal horn in partial sciatic nerve-ligated mice, and this increase was attenuated by GGTI-2133 but not by FTI-277. These results suggest that protein isoprenylation by geranylgeranyl transferase I is involved in the neuropathic pain.