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.
Second Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-machi, Nobeoka-shi, Miyazaki 882-8508, Japan; Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan. Electronic address: ohsawa@phar.nagoya-cu.ac.jp.
Masahiro
M
Ohsawa
Second Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-machi, Nobeoka-shi, Miyazaki 882-8508, Japan.
Junpei
J
Mutoh
Department of Neuropharmacology, Graduate School of Pharmaceutical Sciences, Nagoya City University, 3-1 Tanabe-dori, Mizuho-ku, Nagoya 467-8603, Japan.
Shohei
S
Yamamoto
Second Department of Pharmacology, School of Pharmaceutical Sciences, Kyushu University of Health and Welfare, 1714-1 Yoshino-machi, Nobeoka-shi, Miyazaki 882-8508, Japan.
Hiroaki
H
Hisa
D000818:Animals; D006930:Hyperalgesia / Q000378:metabolism; D007093:Imidazoles / Q000494:pharmacology; D047908:Intracellular Signaling Peptides and Proteins / Q000378:metabolism; D007930:Leucine / Q000031:analogs & derivatives / Q000494:pharmacology; D008297:Male; D008565:Membrane Proteins / Q000378:metabolism; D051379:Mice; D008813:Mice, Inbred ICR; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D009281:Naphthalenes / Q000494:pharmacology; D009437:Neuralgia / Q000209:etiology / Q000378:metabolism*; D010766:Phosphorylation; D017368:Protein Prenylation / Q000502:physiology*; D012584:Sciatic Nerve / Q000293:injuries
C547856:GGTI-2133; D007093:Imidazoles; D047908:Intracellular Signaling Peptides and Proteins; C000619711:Marcks protein, mouse; D008565:Membrane Proteins; D009281:Naphthalenes; D000076250:Myristoylated Alanine-Rich C Kinase Substrate; D007930:Leucine
Allodynia; Hyperalgesia; MARCKS protein; Protein isoprenylation