COX2 in CNS neural cells mediates mechanical inflammatory pain hypersensitivity in mice.
A cardinal feature of peripheral inflammation is pain. The most common way of managing inflammatory pain is to use nonsteroidal antiinflammatory agents (NSAIDs) that reduce prostanoid production, for example, selective inhibitors of COX2. Prostaglandins produced after induction of COX2 in immune cells in inflamed tissue contribute both to the inflammation itself and to pain hypersensitivity, acting on peripheral terminals of nociceptors. COX2 is also induced after peripheral inflammation in neurons in the CNS, where it aids in developing a central component of inflammatory pain hypersensitivity by increasing neuronal excitation and reducing inhibition. We engineered mice with conditional deletion of Cox2 in neurons and glial cells to determine the relative contribution of peripheral and central COX2 to inflammatory pain hypersensitivity. In these mice, basal nociceptive pain was unchanged, as was the extent of peripheral inflammation, inflammatory thermal pain hypersensitivity, and fever induced by lipopolysaccharide. By contrast, peripheral inflammation-induced COX2 expression in the spinal cord was reduced, and mechanical hypersensitivity after both peripheral soft tissue and periarticular inflammation was abolished. Mechanical pain is a major symptom of most inflammatory conditions, such as postoperative pain and arthritis, and induction of COX2 in neural cells in the CNS seems to contribute to this.
Vardeh
Daniel
D
Neural Plasticity Research Group, Department of Anesthesia and Critical Care, Massachusetts General Hospital, Harvard Medical School, Boston, Massachusetts 02129, USA.
Wang
Dairong
D
Costigan
Michael
M
Lazarus
Michael
M
Saper
Clifford B
CB
Woolf
Clifford J
CJ
Fitzgerald
Garret A
GA
Samad
Tarek A
TA
D000818:Animals; D051546:Cyclooxygenase 2 / Q000502:physiology*; D007249:Inflammation / Q000503:physiopathology*; D051379:Mice; D008810:Mice, Inbred C57BL; D018345:Mice, Knockout; D009474:Neurons / Q000201:enzymology*; D010146:Pain / Q000209:etiology*; D013116:Spinal Cord / Q000201:enzymology*
C077623:Ptgs2 protein, mouse; D051546:Cyclooxygenase 2