Veterinary World

     Open access and peer reviewed journal  

ISSN (Online): 2231-0916

ISSN (Print): 0972-8988


Home l Editorial board l Instructions for authors l Reviewer guideline l Open access policy l Archives l FAQ

Open Access

Copyright: The authors. This article is an open access article licensed under the terms of the Creative Commons Attribution License

( which permits unrestricted use, distribution and reproduction in any medium, provided the work is properly cited.

Research (Published online: 07-03-2015)

5. The effect of gabapentin and pregabalin on intestinal incision wound healing in rabbits - M. Korkmaz, T. B. Saritas, A. Sevimli, Z. K. Saritas and B. Elitok

Veterinary World, 8(3): 279-283



   doi: 10.14202/vetworld.2015.279-283


M. Korkmaz: Department of Surgery, Faculty of Veterinary Medicine, Afyon Kocatepe University, 03200, Afyonkarahisar, Turkey;

T. B. Saritas: Department of Anaesthesiology and Reanimation, Meram Medical School, Necmettin Erbakan University, 42080, Konya, Turkey;

A. Sevimli: Department of Pathology, Faculty of Veterinary Medicine, Afyon Kocatepe University, 03200, Afyonkarahisar, Turkey;

Z. K. Saritas: Department of Surgery, Faculty of Veterinary Medicine, Afyon Kocatepe University, 03200, Afyonkarahisar, Turkey;

B. Elitok: Department of Internal Medicine, Faculty of Veterinary Medicine, Afyon Kocatepe University, 03200, Afyonkarahisar, Turkey;


Received: 18-11-2014, Revised: 15-01-2015, Accepted: 25-01-2015, Published online: 07-03-2015


Corresponding author: M. Korkmaz, e-mail:

Citation: Korkmaz M, Saritas TB, Sevimli A, Saritas ZK, Elitok B (2015) The effect of gabapentin and pregabalin on intestinal incision wound healing in rabbits, Veterinary World 8(3):279-283.

Aim: To evaluate the macroscopic and histologic effects of pregabalin (PG) gabapentin (GB) on longitudinal intestinal wound healing in New Zealand rabbits.

Materials and Methods: The animals were divided into three groups randomly; the control group (n=6), PG group (n=6) and GB group (n=6). All animals were premedicated with xylazine HCI, 5 mg/kg i.m. and general anaesthesia was performed by ketamine HCI 50 mg/kg i.m injection. A 4 cm incision in the caecum through median laparotomy was achieved under aseptic surgery. Intestinal wound was closed with double-sutured. All animals were received parenteral antibiotic treatment for 5 days. PG and GB groups were treated by PG (30 mg/kg, oral, daily) and GB (30 mg/kg, oral, daily) for 10 days respectively. Control group did not receive any treatment. The animals were euthanized on day 10 and the caecum was examined by laparotomy. Adhesion formation was observed, and tissue samples were taken from suture lines for histologic examination. Cellular infiltration (polymorphonuclear white blood cells and mononuclear cells), accumulation of connective tissue, vascularization and extent of necrosis were evaluated and scored separately for each of mucosal, submucosal, muscular and serosal layers of caecum.

Results: Adhesions were more severe in the GB group compared to other groups. No statistically significant differences were detected among the three groups about the wound healing.

Conclusion: It was suggested that the use of gabapentinoids had no significant effect on wound healing in patients undergoing gastrointestinal surgery and further studies with treatment periods longer than 10 days are needed.

Keywords: gabapentin, intestinal incisional wound, pregabalin, rabbit.

1. Stadelmann, W.K., Digenis, A.G. and Tobin GR. (1998) Physiology and healing dynamics of chronic cutaneous wounds. Am. J. Surg., 176 2A Suppl: 26-38.
2. Cronin, K., Jackson, D.S. and Dunphy J.E. (1968) Changing bursting strength and collagen content of the healing colon. Surg. Gynecol. Obstet., 126(4): 747-753.
3. Graham, M.F., Drucker, D.E., Diegelmann, R.E. and Elson, C.O. (1987) Collagen synthesis by human intestinal smooth muscle cells in culture. Gastroenterology, 92(2): 400-405.
4. Graham, M.F., Blomguist, P. and Zederfeldt, B. (1992) The alimentary canal. In: Cohen, I.K., Diegelmann, R.F. and Lindblad, W.J. editors. Wound Healing: Biochemical and Clinical Aspects. WB Sunders Company, Philadephia. p433-449.
5. Brasken, P. (1991) Healing of experimental colon anastomoses. Eur. J. Surg., 566: 8-51.
6. Frostberg, E., Ström, P., Gerke, O. and Qvist, N. (2014) Infliximab's influence on anastomotic strength and degree of inflammation in intestinal surgery in a rabbit model. BMC Surg., 14(1): 23.
PMid:24762063 PMCid:PMC4017771
7. Carrico, T.J., Mehrhof Jr, A.I., and Cohen, I.K. (1984) Biology of wound healing. Surg. Clin. North Am., 64(4): 721-733.
8. Gottschalk, A. and Smith, D.S. (2001) New concepts in acute pain therapy: preemptive analgesia. Am. Fam. Physician., 63: 1979-84.
9. Carstensen, M. and Moller, A.M. (2010) Adding ketamine to morphine for intravenous patient controlled analgesia for acute postoperative pain: a qualitative review of randomized trials. Br. J. Anaesth., 104: 401-406.
10. Wood, S. (2010) Postoperative pain 1: understanding the factors affecting patients' experiences of pain. Nurs. Times, 106: 10-13.
11. Chelly, J.E., Ploskanych, T., Dai, F. and Nelson, J.B. (2011) Multimodal analgesic approach incorporating paravertebral blocks for open radical retro-pubic prostatectomy: a randomized double-blind placebo-controlled study. Can. J. Anaesth., 58: 371-8.
12. Gajraj, N.M. (2007) Pregabalin: its pharmacology and use in pain management. Anesth. Analg., 105: 1805-1815.
13. Zhang, J., Ho, K.Y. and Wang, Y. (2011) Efficacy of pregabalin in acute postoperative pain: a meta-analysis. Br. J. Anaesth., 106: 454-462.
14. Kong, V.K. and Irwin, M.G. (2007) Gabapentin A: multimodal perioperative drug? Br. J. Anaesth., 99: 775-786.
15. Tiippana, E.M., Hamunen, K., Kontinen, V.K. and Kalso, E. (2007) Do surgical patients benefit from perioperative gabapentin/pregabalin? A systematic review of efficacy and safety. Anaesth. Analg., 104: 1545-1556.
16. Evans, D.M., McAree, K., Guyton, D.P, Hawkins, N. and Stakleff, K., (1993) Dose dependency and wound healing aspects of the use of tissue plasminogen activator in the prevention of intra-abdominal adhesions. Am. J. Surg., 165: 229-232.
17. Tadros, T., Wobbes, T. and Hendrics, T. (1992) Blood transfusion impairs the healing of experimental intestinal anastomoses. Ann. Surg., 215: 276-281.
PMid:1543401 PMCid:PMC1242433
18. Foster, M.E., Laycock, J.R.D., Silver, I.A. and Leaper, D.J. (1985) Hypovolemia and healing in colonic anastomoses. Br. J. Surg., 72: 831-834.
19. Kologlu, M. and Sayer, I. (1999) Effects of persistently elevated intraabdominal pressure on healing of colonic anastomoses. Am. J. Surg., 178: 293-297.
20. Eubanks, T.R., Greenberg, J.J., Dobrin, P.B., Harford, F.J. and Gamelli, R.L. (1997) The effects of different corticosteroids on the healing colon anastomoses and cecum in rat model. Am. J. Surg., 63: 266-306.
21. Lee, H.J., Kwon, J.Y., Shin, S.W., Baek, S.H., Choi, K.U., Jeon, Y.H. and Baik, S.W. (2010) Effects of sevoflurane on collagen production and growth factor expression in rats with an excision wound. Acta. Anaesthesiol. Scand., 54(7): 885-893.
22. Dere, K., Sen, H., Teksoz, E., Ozkan, S., Dagli, G., Sucullu, I. and Kucukodaci, Z. (2009) The comparison of the effects of different doses of levobupivacaine infiltration on wound healing. Invest. Surg., 22(2): 112-116.
23. Stein, C. and Kuchler, S. (2012) Non-analgesic effects of opioids: peripheral opioid effects on inflammation and wound healing. Curr. Pharm. Des., 18(37): 6053-6069.
24. Sarıtaş, T.B., Korkmaz, M., Sevimli, A. and Sarıtaş, Z.K. (2014) Comparison of the effects of gabapentin and pregabalin on wound healing in rats. Int. Wound J., DOI: 10.1111/iwj.12364.
25. Chambers, W.M. and Mortensen, N.J. (2004) Postoperative leakage and abscess formation after colorectal surgery. Best. Pract. Res. Clin. Gastroenterol., 18(5):865-80.
26. Ott, M.M., Norris, P.R., Diaz, J.J., Collier, B.R., Jenkins, J.M., Gunter, O.L. and Morris, J.A. (2011) Colon anastomosis after damage control laparotomy: recommendations from 174 trauma colectomies. J. Trauma., 70(3): 595-602.
27. Ozel, L., Ozel, M.S., Toros, A.B., Kara, M., Ozkan, K.S., Tellioglu, G. and Berber, I. (2009) Effect of early preoperative 5-fluorouracil on the integrity of colonic anastomoses in rats. World J. Gastroenterol., 15(33): 4156.
PMid:19725150 PMCid:PMC2738812
28. Binnebösel, M., Klink, C.D., Grommes, J., Jansen, M., Neumann, U.P. and Junge, K. (2011) Influence of small intestinal serosal defect closure on leakage rate and adhesion formation: a pilot study using rabbit models. Langenbecks Arch. Surg., 396(1): 133-137.
29. Yang, H., Liang, G., Hawkins, B., Madesh, M., Pierwola, A. and Wei, H. (2008) Inhalational anaesthetics induce cell damage by disruption of intracellular calcium homeostasis with different potencies Anaesthesiology, 109: 243-250.
30. Helmy, S.A. and Al-Attiyah, R.J. (2000) The effects of halothane and isoflurane on plasma cytokine levels. Anaesthesia, 55: 904-910.
31. Sills, G.J. (2006) The mechanisms of action gabapentin and pregabalin. Curr. Opin. Pharmacol., 120: 421-433.
32. Ling, B., Coudore, F., Decalonne, L., Eschalier, A. and Authier N. (2008) Comparative antiallodynic activity of morphine, pregabalin and lidocaine in a rat model of neuropathic pain produced by one oxaliplatin injection. Neuropharmacology, 55: 724-728.
33. Teresiak-Mikołajczak, E., Czarnecka-Operacz, M., Jenerowicz, D. and Silny, W. (2013) Neurogenic markers of the inflammatory process in atopic dermatitis: relation to the severity and pruritus. Postepy. Dermatol. Alergol., 30: 286-292.
PMid:24353488 PMCid:PMC3858656