title: Targeting pain mediators induced by injured nerve-derived COX2 and PGE2 to treat neuropathic pain.
abstract: BACKGROUND
  Neuropathic pain (NeP) is an intractable chronic pain condition which severely deteriorates the quality of life of 6% of the population. Caused by direct physical damage or diseases of the nervous system responsible for pain generation and transmission, NeP is manifested as spontaneous pain, hyperalgesia and allodynia. Its treatment is a challenging and unmet medical need. It is generally accepted that inflammatory mediators over-produced in injured nerves play a crucial role in the initiation and maintenance of NeP.
  
  
  METHODS
  Among numerous inflammatory mediators, cyclooxygenase 2 (COX2) and its end product prostaglandin E2 (PGE2) are persistently up-regulated in infiltrating macrophages and Schwann cells in injured nerves and contribute to the development of NeP. In a NeP rat model and an ex vivo model of sensory ganglion explant culture, injured nerve-derived COX2 and PGE2 facilitate the synthesis of pain mediators including neuropeptides, ion channels, cytokines and neurotrophins in primary sensory neurons.
  
  
  CONCLUSIONS
  Stimulating the synthesis of pain mediators in primary sensory neurons is a novel mechanism underlying the contribution of injured nerve-derived COX2 and PGE2 to the genesis of NeP. Targeting COX2/PGE2/EP signaling in injured nerves through local administration could open a novel therapeutic avenue to treat this debilitating disease.
authors.affiliation: McGill University, Douglas Mental Health University Institute, Montréal, Québec, H4H 1R3, Canada. Weiya.ma@douglas.mcgill.ca
authors.forename: Weiya
authors.initials: W
authors.lastname: Ma
authors.forename: Bruno
authors.initials: B
authors.lastname: St-Jacques
authors.forename: Pedro Cruz
authors.initials: PC
authors.lastname: Duarte
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism*; D015232:Dinoprostone / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000166:cytology; D006801:Humans; D015850:Interleukin-6 / Q000378:metabolism; D009437:Neuralgia / Q000378:metabolism*; D010455:Peptides / Q000378:metabolism; D011984:Sensory Receptor Cells / Q000378:metabolism; D020196:Trauma, Nervous System / Q000378:metabolism*
chemical_list: D015850:Interleukin-6; D010455:Peptides; D051546:Cyclooxygenase 2; D015232:Dinoprostone