Implication of spinal protein kinase Cgamma isoform in activation of the mouse brain by intrathecal injection of the protein kinase C activator phorbol 12,13-dibutyrate using functional magnetic resonance imaging analysis.
The aim of the present study was to investigate whether direct activation of protein kinase C (PKC) in the spinal cord could change brain activation using a functional magnetic resonance imaging (fMRI) analysis in mice that lack the PKCgamma gene. The activation of spinal PKC by intrathecal (i.t.) injection with phorbol 12,13-dibutyrate (PDBu), a specific PKC activator, caused a time-dependent decrease in paw-withdrawal latency to the heat thermal stimulus. In contrast, i.t. injection of PDBu failed to cause thermal hyperalgesia in mice which lacked the PKCgamma gene. We found that the i.t. injection with PDBu caused a remarkable increase in the activity of several brain regions in wild-type mice compared with vehicle injection. In the somatosensory cortex and lateral and medial thalamus, i.t. injection of PDBu produced a dramatic and time-dependent increase in signal intensity at 1-6h after i.t. PDBu injection. In contrast, i.t. injection of PDBu produced a delayed but significant increase in signal intensity at 3-6h in the cingulate cortex, at 4-6h in the nucleus accumbens and at 3-6h in the ventral tegmental area. In addition, all effects of PDBu were abolished in mice that lacked the PKCgamma gene. These results suggest that the activation of spinal PKCgamma associated with the activation of ascending pain transmission may be an important factor in chronic pain-like hyperalgesia with changes in emotionality.
Niikura
Keiichi
K
Department of Toxicology, Hoshi University School of Pharmacy and Pharmaceutical Sciences, 2-4-41 Ebara, Shinagawa-ku, Tokyo 142-8501, Japan.
Kobayashi
Yasuhisa
Y
Okutsu
Daiki
D
Furuya
Masaharu
M
Kawano
Kumi
K
Maitani
Yoshie
Y
Suzuki
Tsutomu
T
Narita
Minoru
M
D000344:Afferent Pathways / Q000187:drug effects / Q000201:enzymology* / Q000503:physiopathology; D000818:Animals; D001921:Brain / Q000201:enzymology* / Q000503:physiopathology; D001931:Brain Mapping; D004644:Emotions / Q000187:drug effects / Q000502:physiology*; D004789:Enzyme Activation / Q000187:drug effects; D020536:Enzyme Activators / Q000494:pharmacology; D006930:Hyperalgesia / Q000139:chemically induced / Q000201:enzymology / Q000235:genetics; D007278:Injections, Spinal; D008279:Magnetic Resonance Imaging; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009475:Neurons, Afferent / Q000187:drug effects / Q000201:enzymology; D009619:Nociceptors / Q000187:drug effects / Q000201:enzymology; D010146:Pain / Q000139:chemically induced / Q000201:enzymology* / Q000235:genetics; D010147:Pain Measurement / Q000187:drug effects; D017288:Pain Threshold / Q000187:drug effects / Q000502:physiology; D015240:Phorbol 12,13-Dibutyrate / Q000494:pharmacology; D011493:Protein Kinase C / Q000187:drug effects / Q000235:genetics / Q000378:metabolism*; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D013997:Time Factors
D020536:Enzyme Activators; D015240:Phorbol 12,13-Dibutyrate; C087857:protein kinase C gamma; D011493:Protein Kinase C