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COX ‐2 is required for the modulation of spinal nociceptive information related to ephrinB/EphB signalling
Author(s) -
Zhou X.L.,
Wang Y.,
Zhang C.J.,
Yu L.N.,
Cao J.L.,
Yan M.
Publication year - 2015
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/ejp.657
Subject(s) - nociception , mapk/erk pathway , hyperalgesia , pharmacology , spinal cord , receptor , allodynia , protein kinase a , kinase , downregulation and upregulation , medicine , chemistry , microbiology and biotechnology , neuroscience , biology , biochemistry , gene
Abstract 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.