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Papers of the Week

2020 May 12

Brain Res

Activation of p38MAPK in spinal microglia contributes to autologous nucleus pulposus-induced mechanical hyperalgesia in a modified rat model of lumbar disk herniation.


Wang Y-M, Gao F-J, Lin S-Q, Yi Z-X, Zhang J-M, Wu H-X, He Q-L, Wei M, Zou X-N, Zhang H, Sun L-B
Brain Res. 2020 May 12:146881.
PMID: 32413357.


Recent studies have implicated the activation of p38 mitogen-activated protein kinase (MAPK) and glial cells contribute to hyperalgesia following nerve injury or nerve compression. In our work, we investigated the underlying mechanisms of autologous nucleus pulposus (NP)-induced mechanical hyperalgesia in a modified rat model of lumbar disk herniation (LDH). Firstly, our results showed that 50% mechanical withdrawal threshold (50% MWT) decreased on postoperative day (POD) 1 and significantly minimally reduced on POD 7and lasted for day 28 after surgery(P<0.05). Secondly, phosphorylation of p38MAPK (p-p38MAPK) and glial cells were monitored on POD 1、3、7、14 and 28 using immunofluorescence staining. P38MAPK activation, observed in the spinal cord, began to increase on POD 1, peaked on POD 3, and significantly decreased on POD 14 and POD 28(P<0.05). Microglia activation was initiated at day 1, maximal at day 3, and maintained until day 14 after surgery(P<0.05). Astrocytic activation was found in 7 to 14 days after modelling(P<0.05). Then, double immunostaining method was applied to observe the co-expression of p-p38MAPK and glial cells, and it showed that p-p38MAPK was mainly expressed in activated microglia, rarely in neurons, and none in astrocytes. Lastly, we discovered that both SB203580 (50ug, p38MAPK inhibitor) and minocycline (0.5mg, microglial inhibitor) would inhibit the p-p38MAPK protein expression tested by western blot analysis and reduce mechanical hyperalgesia. In conclusion, current study suggest that activation or phosphorylation of p38MAPK in spinal microglia contributes to autologous NP-induced mechanical hyperalgesia in our animal model.