title: The time course of inflammatory cytokine secretion in a rat model of postoperative pain does not coincide with the onset of mechanical hyperalgesia.
abstract: We characterized the time course of inflammatory cytokine release at the site of injury and in plasma after surgery on the rat tail. Anesthetized Sprague-Dawley rats had a 20 mm long incision made through the skin and fascia of their tails. Control rats were anesthetized, but no incision was made. Blood and tissue samples were taken 2 h and 1, 2, 4, and 8 days after surgery and analysed by ELISA for interleukin-1beta (IL-1beta), interleukin-6 (IL-6), tumor necrosis factor-alpha (TNF-alpha), and cytokine-induced neutrophil chemoattractant-1 (CINC-1). In another group of rats, daily behavioral measurements were made of the rats' responses to a blunt noxious mechanical stimulus (4 Newtons) applied to their tails. Primary hyperalgesia developed within 2 h of surgery and lasted for 6 days. The tissue concentrations of IL-1beta, IL-6, and CINC-1 increased within 24 h of surgery, and TNF-alpha concentration increased within 48 h of surgery. Thereafter, cytokine concentrations remained elevated for 4 (IL-1beta and IL-6) to 8 days (CINC-1, TNF-alpha) after surgery. Control animals did not develop hyperalgesia and no changes in cytokines concentrations were detected. Thus, in our model of postoperative pain, secretion of inflammatory cytokines IL-1beta, IL-6, TNF-alpha, and CINC-1 was not essential for the initiation of postoperative hyperalgesia.
authors.affiliation: Brain Function Research Group, School of Physiology, University of the Witwatersrand, Johannesburg, 7 York Road, Parktown 2193, South Africa.
authors.forename: Lisa C
authors.initials: LC
authors.lastname: Loram
authors.forename: Andreas C
authors.initials: AC
authors.lastname: Themistocleous
authors.forename: Linda G
authors.initials: LG
authors.lastname: Fick
authors.forename: Peter R
authors.initials: PR
authors.lastname: Kamerman
mesh_terms: D000818:Animals; D054360:Chemokine CXCL1; D019743:Chemokines, CXC / Q000097:blood / Q000378:metabolism; D016207:Cytokines / Q000097:blood / Q000378:metabolism*; D004195:Disease Models, Animal; D004797:Enzyme-Linked Immunosorbent Assay; D005260:Female; D006930:Hyperalgesia / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D007249:Inflammation / Q000097:blood / Q000139:chemically induced / Q000378:metabolism; D018836:Inflammation Mediators / Q000097:blood / Q000378:metabolism*; D053583:Interleukin-1beta / Q000097:blood / Q000378:metabolism; D015850:Interleukin-6 / Q000097:blood / Q000378:metabolism; D008297:Male; D010149:Postoperative Pain / Q000097:blood / Q000378:metabolism / Q000503:physiopathology*; D051381:Rats; D017207:Rats, Sprague-Dawley; D013623:Tail / Q000601:surgery; D013997:Time Factors; D014409:Tumor Necrosis Factor-alpha / Q000097:blood / Q000378:metabolism; D015854:Up-Regulation