Protein phosphatase 2A regulates central sensitization in the spinal cord of rats following intradermal injection of capsaicin.
BACKGROUND
Intradermal injection of capsaicin into the hind paw of rats induces spinal cord central sensititzation, a process in which the responsiveness of central nociceptive neurons is amplified. In central sensitization, many signal transduction pathways composed of several cascades of intracellular enzymes are involved. As the phosphorylation state of neuronal proteins is strictly controlled and balanced by the opposing activities of protein kinases and phosphatases, the involvement of phosphatases in these events needs to be investigated. This study is designed to determine the influence of serine/threonine protein phosphatase type 2A (PP2A) on the central nociceptive amplification process, which is induced by intradermal injection of capsaicin in rats.


RESULTS
In experiment 1, the expression of PP2A protein in rat spinal cord at different time points following capsaicin or vehicle injection was examined using the Western blot method. In experiment 2, an inhibitor of PP2A (okadaic acid, 20 nM or fostriecin, 30 nM) was injected into the subarachnoid space of the spinal cord, and the spontaneous exploratory activity of the rats before and after capsaicin injection was recorded with an automated photobeam activity system. The results showed that PP2A protein expression in the spinal cord was significantly upregulated following intradermal injection of capsaicin in rats. Capsaicin injection caused a significant decrease in exploratory activity of the rats. Thirty minutes after the injection, this decrease in activity had partly recovered. Infusion of a phosphatase inhibitor into the spinal cord intrathecal space enhanced the central sensitization induced by capsaicin by making the decrease in movement last longer.


CONCLUSIONS
These findings indicate that PP2A plays an important role in the cellular mechanisms of spinal cord central sensitization induced by intradermal injection of capsaicin in rats, which may have implications in clinical pain therapy.
Zhang
Xuan
X
Department of Neuroscience and Cell Biology, The University of Texas Medical Branch, 301 University Blvd,, Galveston, TX 77555-1069, USA. xuzhang@utmb.edu
Wu
Jing
J
Lei
Yongzhong
Y
Fang
Li
L
Willis
William D
WD
D000818:Animals; D001522:Behavior, Animal; D002211:Capsaicin / Q000494:pharmacology*; D006801:Humans; D008297:Male; D008954:Models, Biological; D008959:Models, Neurological; D009619:Nociceptors / Q000378:metabolism; D010146:Pain; D010766:Phosphorylation; D054648:Protein Phosphatase 2 / Q000378:metabolism / Q000502:physiology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D018689:Sensory System Agents / Q000494:pharmacology; D013116:Spinal Cord / Q000187:drug effects* / Q000378:metabolism / Q000473:pathology
D018689:Sensory System Agents; D054648:Protein Phosphatase 2; D002211:Capsaicin