A Rat Model of Postoperative Pain

Timothy J. Brennan1

1 University of Iowa College of Medicine, Iowa City, Iowa
Publication Name:  Current Protocols in Pharmacology
Unit Number:  Unit 5.34
DOI:  10.1002/0471141755.ph0534s24
Online Posting Date:  May, 2004
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Research on pain resulting from an incision is crucial for developing therapies for postoperative pain, a condition for which effective and inexpensive treatments are not yet available. Because of the gap between preclinical models of persistent pain (e.g., inflammatory, neuropathic) and acute postsurgical pain, efforts have been undertaken to develop methods for studying pain caused by incisions. To this end, a rat model for postoperative pain has been developed. The model uses a plantar incision in the hindpaw and is characterized by persistent, reduced withdrawal thresholds to mechanical stimuli, as is the case in patients after surgery. The pain behaviors are greatest immediately after recovery from anesthesia. The enhanced responsiveness remains remarkable for several days and then gradually decreases. The model is useful for screening test compounds that may be effective in reducing postoperative pain and for understanding pain mechanisms associated with incisions.

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Table of Contents

  • Commentary
  • Literature Cited
  • Figures
  • Tables
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Basic Protocol 1:

  • 275‐ to 350‐g male Sprague‐Dawley rats (e.g., Harlan)
  • Halothane
  • 10% povidone‐iodine solution (e.g., Clay‐Park Lab)
  • Topical antibiotic ointment (e.g., polymixin B, neomycin, bacitracin)
  • Test compound
  • Vehicle (control)
  • Behavioral testing apparatus (ADPI Enterprises; Fig. ): clear 21 × 27 × 15–cm plastic chamber on an elevated plastic mesh floor with a grid size of 12 × 12 mm
  • Semmes Weinstein nylon (Stoelting) monofilaments with bending forces of ∼14, 30, 42, 65, 73, 98, 149, 265, and 520 mN
  • Sealed box for anesthesia induction
  • Halothane or other volatile anesthetic delivered by a vaporizer
  • Anesthesia nose cone for rat
  • Sterile cloth drape
  • Surgical instruments:
    • Surgical scalpel with no. 11 blade
    • Small curved forceps
    • Needle holders
  • 5‐0 nylon suture on an FS‐2 needle
  • Clean bedding (e.g., Tek Fresh; Harlan)
  • 1‐ml syringes and 25‐G needles
NOTE: All protocols using live animals must first be reviewed and approved by the Institutional Animal Care and Use Committee and must conform to USDA regulations regarding the care and humane use of laboratory animals.
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Literature Cited

   Brennan, T.J. 1999. Postoperative models of nociception. ILAR Journal 40:129‐136.
   Brennan, T.J., Vandermeulen, E., and Gebhart, G.F. 1996. Characterization of a rat model of incisional pain. Pain 64:493‐501.
   Kehlet, H. 1994. Postoperative pain relief—what is the issue? Br. J. Anesth. 72:375‐378.
   Kalso, E. and Rosenberg, P. 1995. Modern trends in postoperative pain. Ann. Med. 27:211‐212.
   Lascelles, B.D., Waterman, A.E., Cripps, P.J., Livingston, A., and Henderson, G. 1995. Central sensitization as a result of surgical pain: Investigation of the pre‐emptive value of pethidine for ovariohysterectomy in the rat. Pain 62:201‐212.
   Lascelles, B.D.X., Cripps, P.J., Jones, A., and Waterman, A.E. 1997. Post‐operative central hypersensitivity and pain—the pre‐emptive value of pethidine for ovariohysterectomy. Pain 73:461‐471.
   Richmond, C.E., Bromley, L.M., and Woolf, C.J. 1993. Preoperative morphine pre‐empts postoperative pain. Lancet 342:73‐75.
   Siegel, S. and Castellan, N.J. 1988. Nonparametric Statistics for the Behavioral Sciences, McGraw‐Hill, New York.
   Stubhaug, A., Breivik, H., Eide, P.K., Kreunen, M., and Foss, A. 1997. Mapping of punctate hyperalgesia around a surgical incision demonstrates that ketamine is a powereful suppressor of central sensitization to pain following surgery. Acta Anaesth Scand 41:1124‐1132.
   Zahn, P.K., Pogatzki, E.M., and Brennan, T.J. 2002. Mechanisms for pain caused by incisions. Reg. Anesth. Pain Med. 27:514‐516.
Key References
   Brennan, T.J. and Zahn, P.K. 2000. Effect of intrathecal ACEA‐1021 in a rat model for postoperative pain. Journal of Pain 1:279‐284.
  Effects of intrathecal drugs on motor and sensory functions after plantar incision were examined.
   Zahn, P.K., Gysbers, D., and Brennan, T.J. 1997. Effect of systemic and intrathecal morphine in a rat model of postoperative pain. Anesthesiology 86:1066‐1077.
  Characterized the effects of a standard analgesic drug, morphine, after incision.
   Zahn, P.K., Umali, E., and Brennan, T.J. 1998. Intrathecal non‐NMDA excitatory amino acid receptor antagonists inhibit pain behaviors in a rat model of postoperative pain. Pain 74:213‐223.
  Motor and sensory function after administration of intrathecal non‐NMDA receptor antagonists were studied in rats undergoing plantar incision.
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