Journal
JOURNAL OF NEUROSCIENCE
Volume 26, Issue 3, Pages 851-861Publisher
SOC NEUROSCIENCE
DOI: 10.1523/JNEUROSCI.3292-05.2006
Keywords
adenylyl cyclases; Erk; spinal dorsal horn; mice; spinal cord; glutamate; substance P; cyclic Amp; Camp; C-Amp
Categories
Funding
- PHS HHS [42733] Funding Source: Medline
Ask authors/readers for more resources
The extracellular signal-regulated kinase (Erk) cascades are suggested to contribute to excitatory synaptic plasticity in the CNS, including the spinal cord dorsal horn. However, many of their upstream signaling pathways remain to be investigated. Here, we demonstrate that glutamate and substance P (SP), two principal mediators of sensory information between primary afferent fibers and the spinal cord, activate Erk in dorsal horn neurons of both adult rat and mouse spinal cord. In genetic knock-out mice of calcium calmodulin-stimulated adenylyl cyclase subtypes 1 (AC1) and 8(AC8), activation of Erk in dorsal horn neurons were significantly reduced or blocked, either after peripheral tissue inflammation or by glutamate or SP in spinal cord slices. Our studies suggest that AC1 and AC8 act upstream from Erk activation in spinal dorsal horn neurons and the calcium-AC1/AC8-dependent Erk signaling pathways may contribute to spinal sensitization, an underlying mechanism for the development of persistent pain after injury.
Authors
I am an author on this paper
Click your name to claim this paper and add it to your profile.
Reviews
Recommended
No Data Available