Developmental differences in spinal cyclooxygenase 1 expression after surgical incision.
BACKGROUND
Systemic administration of a cyclooxygenase 1 (COX-1) inhibitor reduces hypersensitivity to mechanical stimuli after incisional paw surgery in 4-week-old, but not 2-week-old, animals. The purpose of the current study was to test whether this developmental difference was reflected by differences in COX-1 expression in the spinal cord after surgery.


METHODS
Rats 2 and 4 weeks of age, paralleling infant and child human neurologic developmental stages, were used. A paw incision was made under general anesthesia and the withdrawal thresholds were measured before and after systemic and intrathecal administration of a COX-1 selective inhibitor (SC560). Immunohistochemistry was used to assess COX-1 protein in the spinal cord, and real-time polymerase chain reaction was used to quantify gene expression of COX-1 mRNA.


RESULTS
Systemic and intrathecal administration of SC560 produced an increase in withdrawal threshold in the 4-week-old, but not in the 2-week-old, animals. Intrathecal SC560 increased withdrawal thresholds in the 4-week-old animals at a dose 100-fold less than with systemic administration. Cyclooxygenase 1 protein in the spinal cord was increased ipsilateral to surgery in the 4-week-old, but not in the 2-week-old, animals. Cyclooxygenase 1 mRNA was increased in the 4-week-old animals in the spinal cord ipsilateral to surgery relative to the contralateral side of the spinal cord, but not in the 2-week-old animals.


CONCLUSIONS
These results suggest that developmental differences in COX-1 expression in the spinal cord likely explain the lack of efficacy of COX-1 inhibitors in the 2-week-old rats. Whether this reflects a deficit in factors that stimulate COX-1 expression or a difference in response to these factors is not addressed, but should similar deficits occur in humans, COX-1 inhibitors may exhibit reduced efficacy in infants.
Ririe
Douglas G
DG
Department of Anesthesiology and Center for the Study of Pharmacological Plasticity in the Presence of Pain, Wake Forest University School of Medicine, Winston-Salem, North Carolina 27157-1009, USA. dririe@wfubmc
Prout
Heather D
HD
Barclay
David
D
Tong
Chuanyo
C
Lin
Marina
M
Eisenach
James C
JC
D000367:Age Factors; D000818:Animals; D051545:Cyclooxygenase 1 / Q000032:analysis* / Q000235:genetics; D007150:Immunohistochemistry; D008297:Male; D016133:Polymerase Chain Reaction; D011720:Pyrazoles / Q000494:pharmacology; D012333:RNA, Messenger / Q000032:analysis; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000201:enzymology*; D013514:Surgical Procedures, Operative
D011720:Pyrazoles; D012333:RNA, Messenger; C115461:SC 560; D051545:Cyclooxygenase 1