ggti-2133 and Neuralgia

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.

Topics: Animals; Hyperalgesia; Imidazoles; Intracellular Signaling Peptides and Proteins; Leucine; Male; Membrane Proteins; Mice; Mice, Inbred ICR; Myristoylated Alanine-Rich C Kinase Substrate; Naphthalenes; Neuralgia; Phosphorylation; Protein Prenylation; Sciatic Nerve