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The contribution of autophosphorylated alpha-calcium-calmodulin kinase II to injury-induced persistent pain.
- Source :
-
Neuroscience [Neuroscience] 2004; Vol. 128 (4), pp. 889-98. - Publication Year :
- 2004
-
Abstract
- Increases in neuronal activity in response to tissue or nerve injury can lead to prolonged functional changes in the spinal cord resulting in an enhancement/sensitization of nociceptive processing. To assess the contribution of alpha-calcium-calmodulin kinase II (alpha-CaMKII) to injury-induced inflammation and pain, we evaluated nociceptive responses in mice that carry a point mutation in the alpha-CaMKII gene at position 286 (threonine to alanine). The mutated protein is unable to autophosphorylate and thus cannot function independently of calcium and calmodulin. Responses to acute noxious stimuli did not differ between alpha-CaMKII T286A mutant and wild type mice. However, the ongoing pain produced by formalin injury was significantly reduced in the mutant mice, as was formalin-evoked spinal Fos-immunoreactivity. In contrast, the decreased mechanical and thermal thresholds associated with nerve injury, Complete Freund's Adjuvant-induced inflammation or formalin-evoked tissue injury were manifest equally in wild-type and mutant mice. Double-labeling immunofluorescence studies revealed that in the mouse alpha-CaMKII is expressed in the superficial dorsal horn as well as in a population of small diameter primary afferent neurons. In summary, our results suggest that alpha-CaMKII, perhaps secondary to an N-methyl-D-aspartate-mediated calcium increase in postsynaptic dorsal horn nociresponsive neurons, is a critical contributor to the spontaneous/ongoing component of tissue-injury evoked persistent pain.
- Subjects :
- Animals
Behavior, Animal
Calcium metabolism
Calcium-Calmodulin-Dependent Protein Kinase Type 2
Calcium-Calmodulin-Dependent Protein Kinases genetics
Calcium-Calmodulin-Dependent Protein Kinases metabolism
Cell Count methods
Edema pathology
Freund's Adjuvant
Ganglia, Spinal metabolism
Glycoproteins metabolism
Immunohistochemistry methods
Intermediate Filament Proteins metabolism
Membrane Glycoproteins metabolism
Mice
Mice, Inbred C57BL
Mice, Mutant Strains
Nerve Tissue Proteins metabolism
Nociceptors physiology
Oncogene Proteins v-fos metabolism
Pain etiology
Pain Measurement
Pain Threshold
Peripherins
Phosphorylation
Physical Stimulation methods
Protein Kinase C metabolism
Reaction Time genetics
Substance P metabolism
Time Factors
Trigeminal Ganglion metabolism
Calcium-Calmodulin-Dependent Protein Kinases physiology
Pain enzymology
Wounds and Injuries complications
Subjects
Details
- Language :
- English
- ISSN :
- 0306-4522
- Volume :
- 128
- Issue :
- 4
- Database :
- MEDLINE
- Journal :
- Neuroscience
- Publication Type :
- Academic Journal
- Accession number :
- 15464294
- Full Text :
- https://doi.org/10.1016/j.neuroscience.2004.07.029