Behavioural neuroscienceDifferential expression of phosphorylated Ca2+/calmodulin-dependent protein kinase II and phosphorylated extracellular signal-regulated protein in the mouse hippocampus induced by various nociceptive stimuli
Section snippets
Experimental procedures
These experiments were approved by the Hallym University Animal Care and Use Committee. All procedures were conducted in accordance with the ‘Guide for Care and Use of Laboratory Animals’ published by the National Institutes of Health and the ethical guidelines of the International Association for the Study of Pain. We did our best to minimize the number of animals used and their suffering.
The effect of various nociceptive stimuli on pERK1/2 and pCaMK-IIα expression in the mouse hippocampus
All Western blot data shown in this study were from experiments repeated at least three times (the same three mice tested three times). To examine the effects of various nociceptive stimuli (1% acetic acid i.p. injection, 5% formalin s.c. injection, glutamate i.t. injection, and proinflammatory cytokines i.t. injection) on the hippocampal pCaMKIIα (53 kDa) and pERK1/2 (44 and 42 kDa) expression, Western blot analysis was performed at various time points (30 min, 1 h, and 2 h) after nociceptive
Discussion
We have tested the hypothesis that the hippocampal pCaMK-IIα and pERK1/2 are involved in nociceptive processing. We found that the expressions of pCaMK-IIα and pERK1/2 were significantly increased by various nociceptive stimuli. In addition, supraspinally administered CaMK-II inhibitor (KN-93) as well as MEK1/2 inhibitor (PD98059) significantly attenuated the nociceptive behaviors induced by i.p. acetic acids, i.t. glutamate, TNF-α, and IL-1β injection. Although the differential antinociceptive
Conclusion
In conclusion, the present data demonstrated that nociceptive stimuli induced by formalin, acetic acid, glutamate, and pro-inflammatory cytokines activate the hippocampal pCaMK-IIα and pERK1/2 molecules in a different manner, and these results suggest that alterations of hippocampal pCaMK-IIα and pERK1/2 may play an important role in supraspinal nociceptive processing.
Acknowledgments
This research was supported by research grants from the Korean Ministry of Science and Technology under the auspices of Brain Frontier (M103KV010014-08K2201-01410) and the MRC program of MOST/KOSEF (R13-2005-022-03002-0).
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2015, European Journal of PharmacologyCitation Excerpt :Corroborating this idea, Al Amin et al. (2004) demonstrated that neonatal hippocampal lesion in rats increased the nociceptive sensitivity in adulthood. The fact that the nociceptive stimulus induced by glutamate activates the hippocampal pERK1/2 molecules in supraspinal nociceptive processing (Seo et al., 2008) and that injections of MK-801 to the hippocampus produces an analgesic effect (Mckenna and Melzack, 1992) helps to explain how a neonatal injection of MSG leads changes in the glutamatergic neurotransmission within the hippocampus 60 days after. Glutamate is a critical neurotransmitter for excitatory synaptic transmission and for the generation and maintenance of pain hypersensitivity via activation of glutamate receptors (Basbaum et al., 2009).
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