Activation of p38 mitogen-activated protein kinase in spinal microglia contributes to incision-induced mechanical allodynia.
BACKGROUND
Recent studies have implicated the activation of stress-activated mitogen-activated protein kinase (MAPK) p38 in spinal microglial cells for development of neuropathic and inflammatory pain. The aim of the present study was to investigate whether phosphorylation of p38 (p-p38) also mediates mechanical allodynia and thermal hyperalgesia induced by plantar incision.


METHODS
After rats received a plantar incision surgery, mechanical allodynia and thermal hyperalgesia were determined by von Frey filaments and radiant heat, respectively, and the number of p-p38 immunoreactive cells in the dorsal horn was quantified to determine p38 activation at different time points after incision. The p38 inhibitor FR167653 was administered intrathecally 30 min before hind paw plantar incision to determine the role of p38 in postoperative pain.


RESULTS
A significant increase in number of p-p38 immunoreactive cells was observed in the ipsilateral L4-5 spinal dorsal horn from 1 h to 3 days after the incision. p-p38 was found predominantly in microglia. However, microglial activation (assessed by OX-42 upregulation) was not evident until 3 days after plantar incision. Intrathecal pretreatment of FR167653 attenuated incision-induced mechanical allodynia from 1 h to day 2 and significantly reduced activation of p38 in the dorsal horn 1 day after plantar incision. However, FR167653 only inhibited heat hyperalgesia at an early time point.


CONCLUSIONS
Plantar incision-induced mechanical allodynia can be prevented by the p38 inhibitor. Our results suggest that p38 activation in spinal microglia play a role in incision-induced mechanical allodynia in rats. Therefore, p38 inhibition may be useful in treating postsurgical pain.
Wen
Yeong-Ray
YR
Graduate Institute of Medical Sciences, and School of Medicine, Taipei Medical University, Taipei, Taiwan.
Suter
Marc R
MR
Ji
Ru-Rong
RR
Yeh
Geng-Chang
GC
Wu
Yen-Sheng
YS
Wang
Kuo-Ching
KC
Kohno
Tatsuro
T
Sun
Wei-Zen
WZ
Wang
Chia-Chuan
CC
D000818:Animals; D004789:Enzyme Activation / Q000187:drug effects / Q000502:physiology; D008297:Male; D017628:Microglia / Q000187:drug effects / Q000201:enzymology*; D010146:Pain / Q000201:enzymology* / Q000517:prevention & control; D010147:Pain Measurement / Q000187:drug effects / Q000295:instrumentation / Q000379:methods*; D010812:Physical Stimulation / Q000379:methods; D011720:Pyrazoles / Q000494:pharmacology / Q000627:therapeutic use; D011725:Pyridines / Q000494:pharmacology / Q000627:therapeutic use; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000187:drug effects / Q000201:enzymology*; D048051:p38 Mitogen-Activated Protein Kinases / Q000037:antagonists & inhibitors / Q000378:metabolism*
C104334:FR 167653; D011720:Pyrazoles; D011725:Pyridines; D048051:p38 Mitogen-Activated Protein Kinases