| First Author | Saha M | Year | 2013 |
| Journal | J Neurosci | Volume | 33 |
| Issue | 43 | Pages | 17182-7 |
| PubMed ID | 24155322 | Mgi Jnum | J:204669 |
| Mgi Id | MGI:5538419 | Doi | 10.1523/JNEUROSCI.5605-12.2013 |
| Citation | Saha M, et al. (2013) Spinal mitogen-activated protein kinase phosphatase-3 (MKP-3) is necessary for the normal resolution of mechanical allodynia in a mouse model of acute postoperative pain. J Neurosci 33(43):17182-7 |
| abstractText | The mechanisms that drive the normal resolution of acute postoperative pain are not completely understood. We hypothesize a pivotal role of a major spinal mitogen-activated protein kinase (MAPKs) regulator, MAPK phosphatase (MKP)-3, in the resolution of postoperative pain. We used wild-type and MKP-3 knock-out (KO) mice, a paw incision model of acute postoperative pain, and behavioral and molecular biology experiments. We observed persistent mechanical allodynia in mice lacking MKP-3 (postoperative day 21), concurrently with persistent phosphorylation of spinal p38 and extracellular signal-regulated kinases (ERK)-1/2 on postoperative day 12, while both MAPK phosphorylation and allodynia resolved on postoperative day 7 in wild-type mice. Spinal p-ERK was expressed mainly in neurons and microglia, while spinal p-p38 was expressed mostly in microglia in MKP-3 KO mice, and their selective pharmacological inhibition reduced the persistent allodynia observed in these mice. Our findings strongly suggest that dysregulation of MKP-3 prevents spontaneous resolution of acute postoperative pain and drives its transition to persistent pain via persistent neuronal and microglial MAPK phosphorylation in the spinal cord. |
