COX-2 is required for the modulation of spinal nociceptive information related to ephrinB/EphB signalling.
BACKGROUND
EphB receptors and their ephrinB ligands are implicated in modulating spinal nociceptive information processing. Here, we investigated whether cyclooxygenase-2 (COX-2), acts as a downstream effector, participates in the modulation of spinal nociceptive information related to ephrinB/EphB signalling.


METHODS
Thermal hyperalgesia and mechanical allodynia were measured by using radiant heat and von Frey filaments test, respectively. Real-time PCR (RT-PCR) was used to detect the expression of spinal COX-2 mRNA. Spinal COX-2 and extracellular signal-regulated kinase (ERK) protein were determined by Western blot analysis.


RESULTS
Intrathecal injection of ephrinB2-Fc caused thermal hyperalgesia and mechanical allodynia, which were accompanied by increased expression of spinal COX-2 mRNA and protein. Inhibition of spinal COX-2 prevented and reversed pain behaviours induced by the intrathecal injection of ephrinB2-Fc. Blockade of EphB receptors by intrathecal injection of EphB2-Fc reduced complete Freund's adjuvant (CFA)-induced inflammatory pain behaviours, which were accompanied by decreased expression of spinal COX-2 mRNA and protein. Furthermore, treatment with U0126, a mitogen-activated protein/extracellular signal-regulated kinase kinase (MEK) inhibitor, suppressed spinal ERK activation and COX-2 mRNA and protein expression induced by intrathecal injection of ephrinB1-Fc.


CONCLUSIONS
These results confirmed the important involvement of COX-2 in the modulation of spinal nociceptive information related to ephrinBs-EphBs signalling.
Department of Anesthesiology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
X-L
XL
Zhou
Jiangsu Province Key Laboratory of Anesthesilogy, Xuzhou Medical College, China.
Y
Y
Wang
Department of Gastroenterology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
C-J
CJ
Zhang
Department of Anesthesiology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.
L-N
LN
Yu
Jiangsu Province Key Laboratory of Anesthesilogy, Xuzhou Medical College, China.
J-L
JL
Cao
Department of Anesthesiology, School of Medicine, The Second Affiliated Hospital, Zhejiang University, Hangzhou, China.|Jiangsu Province Key Laboratory of Anesthesilogy, Xuzhou Medical College, China.
M
M
Yan
D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D004195:Disease Models, Animal; D036388:Ephrin-B2 / Q000008:administration & dosage / Q000378:metabolism*; D048049:Extracellular Signal-Regulated MAP Kinases / Q000378:metabolism*; D006930:Hyperalgesia / Q000139:chemically induced / Q000175:diagnosis / Q000378:metabolism*; D008297:Male; D051379:Mice; D008810:Mice, Inbred C57BL; D059225:Nociception / Q000502:physiology*; D012333:RNA, Messenger / Q000378:metabolism; D036081:Receptors, Eph Family / Q000187:drug effects / Q000378:metabolism*; D015398:Signal Transduction / Q000502:physiology*; D013116:Spinal Cord / Q000378:metabolism*
D036388:Ephrin-B2; D012333:RNA, Messenger; D051546:Cyclooxygenase 2; D036081:Receptors, Eph Family; D048049:Extracellular Signal-Regulated MAP Kinases