title: Local anaesthetics attenuates spinal nociception and HPA-axis activation during experimental laparotomy in pigs.
abstract: The effect of local anaesthetics on spinal nociception and activation of the hypothalamic-pituitary-adrenal axis (HPA-axis) was examined in a porcine model of abdominal surgery. A standardised laparotomy without visceral involvement was performed on 24 pigs. One group received a unilateral infiltration of mixed lidocaine and bupivacaine in skin, muscle and peritoneum of the surgical area prior to surgery (n=12), while local anaesthetics were replaced by isotonic saline in a second group (n=12). A sham group was subjected to anaesthesia (n=8), but did not undergo surgery. Two hours after surgery, half of the pigs from each group were perfused with formalin and the spinal cord was taken out for stereological quantification of the total number of Fos-like-immunoreactive (Fos-LI) neurones in the dorsal horn. Surgery with saline gave rise to a significant increase in the number of Fos-LI neurones ipsilaterally (107,001+/-16,548; p<0.001) as well as contralaterally (12,766+/-3,842; p<0.01) compared to the sham group. In animals undergoing surgery with LA, the number of Fos-LI neurones ipsilaterally was not significantly different from the sham group (p=0.78), and was reduced significantly both ipsilaterally (6960+/-1662; p<0.001) and contralaterally (3974+/-1131; p<0.05) compared to the saline group. In the other half of each group, blood samples, for determination of ACTH, cortisol, C-reactive protein and interleukin-6 concentrations, were drawn prior to and at predetermined time-points during and after surgery. Surgery with saline gave rise to dramatic increases in plasma ACTH and cortisol (p<0.01 and p<0.001, respectively) within 15 min of incision. In contrast, no changes from the initial concentrations of ACTH and cortisol were observed in pigs receiving local anaesthetics. No changes in plasma concentrations of C-reactive protein or interleukin-6 were observed in either of the groups. These results indicate that spinal nociception and HPA-axis activation caused by laparotomy in pigs can be attenuated by use of infiltration and incisional local anaesthetics prior to surgery. The present model provides a valuable tool in the evaluation of analgesic treatment during surgery, offering objective measures of both nociception and stress.
authors.affiliation: Department of Pharmacology and Pathobiology, The Royal Veterinary and Agricultural University, 9 Ridebanevej, DK-1870 Frederiksberg C, Copenhagen, Denmark. kl@rheoscience.com
authors.forename: K
authors.initials: K
authors.lastname: Lykkegaard
authors.forename: B
authors.initials: B
authors.lastname: Lauritzen
authors.forename: L
authors.initials: L
authors.lastname: Tessem
authors.forename: P
authors.initials: P
authors.lastname: Weikop
authors.forename: O
authors.initials: O
authors.lastname: Svendsen
mesh_terms: D000324:Adrenocorticotropic Hormone / Q000097:blood; D000772:Anesthesia, Local / Q000662:veterinary*; D000779:Anesthetics, Local / Q000627:therapeutic use*; D000818:Animals; D002045:Bupivacaine / Q000627:therapeutic use; D002097:C-Reactive Protein / Q000378:metabolism; D004195:Disease Models, Animal; D005260:Female; D006854:Hydrocortisone / Q000097:blood; D007030:Hypothalamo-Hypophyseal System / Q000187:drug effects*; D015850:Interleukin-6 / Q000097:blood; D007813:Laparotomy / Q000662:veterinary*; D008012:Lidocaine / Q000627:therapeutic use; D008297:Male; D010146:Pain / Q000188:drug therapy* / Q000503:physiopathology* / Q000662:veterinary; D010913:Pituitary-Adrenal System / Q000187:drug effects*; D013552:Swine / Q000502:physiology; D013553:Swine Diseases / Q000188:drug therapy / Q000503:physiopathology
chemical_list: D000779:Anesthetics, Local; D015850:Interleukin-6; D000324:Adrenocorticotropic Hormone; D002097:C-Reactive Protein; D008012:Lidocaine; D006854:Hydrocortisone; D002045:Bupivacaine