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Development and Characterization of a Novel, Anatomically Relevant Rat Model of Acute Postoperative Pain

  • Dara Bree
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Discipline of Physiology, School of Medicine, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • Orla Moriarty
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Discipline of Physiology, School of Medicine, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Research and Development, Covidien, North Haven, Connecticut
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  • Cliona M. O'Mahony
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Discipline of Physiology, School of Medicine, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Research and Development, Covidien, North Haven, Connecticut
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  • Bradley Morris
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Discipline of Physiology, School of Medicine, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • Karen Bannerton
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • Daniel C. Broom
    Affiliations
    Research and Development, Covidien, North Haven, Connecticut
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  • John P. Kelly
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • Michelle Roche
    Affiliations
    Discipline of Physiology, School of Medicine, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
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  • David P. Finn
    Correspondence
    Address reprint requests to David P. Finn, PhD, Pharmacology and Therapeutics, School of Medicine, University Road, National University of Ireland, Galway, Ireland.
    Affiliations
    Discipline of Pharmacology and Therapeutics, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland

    Galway Neuroscience Centre and Centre for Pain Research, National Centre for Biomedical Engineering Science, National University of Ireland, Galway, Ireland
    Search for articles by this author
Published:January 29, 2015DOI:https://doi.org/10.1016/j.jpain.2015.01.010

      Highlights

      • A novel rat model of acute postoperative pain has been developed.
      • It represents the first animal model of acute pain following inguinal hernia repair.
      • The model is characterized by deficits in locomotor activity, reversible by analgesics.
      • Pain-related phenotype is driven primarily by activation of deep somatic or visceral nociceptors.
      • The model is associated with increased c-Fos expression in the dorsal horn.

      Abstract

      Acute postoperative pain remains a significant health care issue. Development of anatomically relevant animal models of postoperative pain, with improved predictive validity, would advance understanding of postoperative pain mechanisms and improve treatment outcomes. This study aimed to develop, characterize, and validate a rat model of acute postoperative pain associated with inguinal hernia repair based on the Lichtenstein inguinal hernia repair procedure (without hernia induction). We hypothesized that the surgery would result in reduced spontaneous locomotor activity, which would represent a pain-related phenotype. Postsurgical characterization involved extensive monitoring of home cage and open field locomotor activity, as well as mechanical hypersensitivity and assessment of c-Fos expression in the dorsal horn of the spinal cord. In pharmacologic validation studies, rats received morphine, carprofen, or paracetamol 1 hour before, and/or immediately after, surgery. Rats that underwent hernia repair surgery exhibited significantly lower horizontal and vertical activities in the home cage and open field in the early postsurgical period, compared with sham rats or rats that underwent skin incision only. Morphine, carprofen, and paracetamol attenuated the surgery-induced reductions in locomotor activity, to varying degrees. Surgery was associated with significantly increased c-Fos expression in the ipsilateral dorsal horn of the spinal cord, an effect attenuated by carprofen treatment. These results support the development and characterization of a novel, anatomically relevant animal model of acute postoperative pain that may facilitate development of improved treatment regimens.

      Perspective

      Acute pain following inguinal hernia repair can be difficult to treat. Here we report, for the first time, the development of a novel, anatomically relevant rat model to facilitate improved understanding and treatment of acute postoperative pain following inguinal hernia repair.

      Key words

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      References

        • Aasvang E.K.
        • Bay-Nielsen M.
        • Kehlet H.
        Pain and functional impairment 6 years after inguinal herniorrhaphy.
        Hernia. 2006; 10: 316-321
        • Adamson T.W.
        • Kendall L.V.
        • Goss S.
        • Grayson K.
        • Touma C.
        • Palme R.
        • Chen J.Q.
        • Borowsky A.D.
        Assessment of carprofen and buprenorphine on recovery of mice after surgical removal of the mammary fat pad.
        J Am Assoc Lab Anim Sci. 2010; 49: 610-616
        • American Society of Anesthesiologists Task Force on Acute Pain Management
        Practice guidelines for acute pain management in the perioperative setting: an updated report by the American Society of Anesthesiologists Task Force on Acute Pain Management.
        Anesthesiology. 2012; 116: 248-273
        • Amid P.K.
        The Lichtenstein repair in 2002: an overview of causes of recurrence after Lichtenstein tension-free hernioplasty.
        Hernia. 2003; 7: 13-16
        • Amid P.K.
        • Shulman A.G.
        • Lichtenstein I.L.
        The Lichtenstein open “tension-free” mesh repair of inguinal hernias.
        Surg Today. 1995; 25: 619-625
        • Apfelbaum J.L.
        • Chen C.
        • Mehta S.S.
        • Gan T.J.
        Postoperative pain experience: results from a national survey suggest postoperative pain continues to be undermanaged.
        Anesth Analg. 2003; 97 (table of contents, 2003): 534-540
        • Brennan T.J.
        • Vandermeulen E.P.
        • Gebhart G.F.
        Characterization of a rat model of incisional pain.
        Pain. 1996; 64: 493-501
        • Buvanendran A.
        • Kroin J.S.
        • Kari M.R.
        • Tuman K.J.
        A new knee surgery model in rats to evaluate functional measures of postoperative pain.
        Anesth Analg. 2008; 107: 300-308
        • Chaplan S.R.
        • Bach F.W.
        • Pogrel J.W.
        • Chung J.M.
        • Yaksh T.L.
        Quantitative assessment of tactile allodynia in the rat paw.
        J Neurosci Methods. 1994; 53: 55-63
        • Duarte A.M.
        • Pospisilova E.
        • Reilly E.
        • Mujenda F.
        • Hamaya Y.
        • Strichartz G.R.
        Reduction of postincisional allodynia by subcutaneous bupivacaine: findings with a new model in the hairy skin of the rat.
        Anesthesiology. 2005; 103: 113-125
        • Faas C.L.
        • Acosta F.J.
        • Campbell M.D.
        • O'Hagan C.E.
        • Newton S.E.
        • Zagalaniczny K.
        The effects of spinal anesthesia vs epidural anesthesia on 3 potential postoperative complications: pain, urinary retention, and mobility following inguinal herniorrhaphy.
        AANA J. 2002; 70: 441-447
        • Flatters S.J.
        Characterization of a model of persistent postoperative pain evoked by skin/muscle incision and retraction (SMIR).
        Pain. 2008; 135: 119-130
        • Furedi R.
        • Bolcskei K.
        • Szolcsanyi J.
        • Petho G.
        Effects of analgesics on the plantar incision-induced drop of the noxious heat threshold measured with an increasing-temperature water bath in the rat.
        Eur J Pharmacol. 2009; 605: 63-67
        • Gilron I.
        • Orr E.
        • Tu D.
        • O'Neill J.P.
        • Zamora J.E.
        • Bell A.C.
        A placebo-controlled randomized clinical trial of perioperative administration of gabapentin, rofecoxib and their combination for spontaneous and movement-evoked pain after abdominal hysterectomy.
        Pain. 2005; 113: 191-200
        • Gourgiotis S.
        • Germanos S.
        • Stratopoulos C.
        • Moustafellos P.
        • Panteli A.
        • Hadjiyannakis E.
        Lichtenstein tension-free repair of inguinal hernia.
        Chirurgia (Bucur). 2006; 101: 509-512
        • Jenkins J.T.
        • O'Dwyer P.J.
        Inguinal hernias.
        BMJ. 2008; 336: 269-272
        • Kim S.H.
        • Chung J.M.
        An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat.
        Pain. 1992; 50: 355-363
        • Lichtenstein I.L.
        • Shulman A.G.
        • Amid P.K.
        • Willis P.A.
        Hernia repair with polypropylene mesh. An improved method.
        AORN J. 1990; 52: 559-565
        • Magnus-Ellenbroek B.
        • Havemann-Reinecke U.
        Morphine-induced hyperactivity in rats—A rebound effect?.
        Naunyn Schmiedebergs Arch Pharmacol. 1993; 347: 635-642
        • Martin T.J.
        • Buechler N.L.
        • Kahn W.
        • Crews J.C.
        • Eisenach J.C.
        Effects of laparotomy on spontaneous exploratory activity and conditioned operant responding in the rat: a model for postoperative pain.
        Anesthesiology. 2004; 101: 191-203
        • Massaron S.
        • Bona S.
        • Fumagalli U.
        • Battafarano F.
        • Elmore U.
        • Rosati R.
        Analysis of post-surgical pain after inguinal hernia repair: a prospective study of 1,440 operations.
        Hernia. 2007; 11: 517-525
        • Matson D.J.
        • Broom D.C.
        • Carson S.R.
        • Baldassari J.
        • Kehne J.
        • Cortright D.N.
        Inflammation-induced reduction of spontaneous activity by adjuvant: A novel model to study the effect of analgesics in rats.
        J Pharmacol Exp Ther. 2007; 320: 194-201
        • McGrath B.
        • Elgendy H.
        • Chung F.
        • Kamming D.
        • Curti B.
        • King S.
        Thirty percent of patients have moderate to severe pain 24 hr after ambulatory surgery: a survey of 5,703 patients.
        Can J Anaesth. 2004; 51: 886-891
        • Miranda H.F.
        • Puig M.M.
        • Prieto J.C.
        • Pinardi G.
        Synergism between paracetamol and nonsteroidal anti-inflammatory drugs in experimental acute pain.
        Pain. 2006; 121: 22-28
        • Moriarty O.
        • Roche M.
        • McGuire B.E.
        • Finn D.P.
        Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain.
        J Neurosci Methods. 2012; 204: 1-8
        • Ramsay M.A.
        Acute postoperative pain management.
        Proc (Bayl Univ Med Cent). 2000; 13: 244-247
        • Rea K.
        • Roche M.
        • Finn D.P.
        Modulation of conditioned fear, fear-conditioned analgesia, and brain regional c-Fos expression following administration of muscimol into the rat basolateral amygdala.
        J Pain. 2011; 12: 712-721
        • Roche M.
        • Johnston P.
        • Mhuircheartaigh O.N.
        • Olango W.M.
        • Mackie K.
        • Finn D.P.
        Effects of intra-basolateral amygdala administration of rimonabant on nociceptive behaviour and neuronal activity in the presence or absence of contextual fear.
        Eur J Pain. 2010; 14: 487-495
        • Roughan J.V.
        • Flecknell P.A.
        Behavioural effects of laparotomy and analgesic effects of ketoprofen and carprofen in rats.
        Pain. 2001; 90: 65-74
        • Roughan J.V.
        • Flecknell P.A.
        Effects of surgery and analgesic administration on spontaneous behaviour in singly housed rats.
        Res Vet Sci. 2000; 69: 283-288
        • Roughan J.V.
        • Flecknell P.A.
        Evaluation of a short duration behaviour-based post-operative pain scoring system in rats.
        Eur J Pain. 2003; 7: 397-406
        • Roughan J.V.
        • Flecknell P.A.
        • Davies B.R.
        Behavioural assessment of the effects of tumour growth in rats and the influence of the analgesics carprofen and meloxicam.
        Lab Anim. 2004; 38: 286-296
        • Rowe M.I.
        • Copelson L.W.
        • Clatworthy H.W.
        The patent processus vaginalis and the inguinal hernia.
        J Pediatr Surg. 1969; 4: 102-107
        • Sakorafas G.H.
        • Halikias I.
        • Nissotakis C.
        • Kotsifopoulos N.
        • Stavrou A.
        • Antonopoulos C.
        • Kassaras G.A.
        Open tension free repair of inguinal hernias; the Lichtenstein technique.
        BMC Surg. 2001; 1: 3
        • Smith K.L.
        • Roche M.
        • Jessop D.S.
        • Finn D.P.
        The effects of synthetic and endogenous imidazoline binding site ligands on neuronal activity in discrete brain regions of naive and restraint-stressed rats.
        Eur Neuropsychopharmacol. 2009; 19: 371-380
        • St A.S.L.
        • Martin W.J.
        Evaluation of postoperative analgesia in a rat model of incisional pain.
        Contemp Top Lab Anim Sci. 2003; 42: 28-34
        • Watson C.
        • Paxinos G.
        • Kayalioglu G.
        • Heise C.
        • Charles W.
        • George P.
        • Gulgun Kayalioglu A.2
        • Charles Watson G.P.
        • Gulgun K.
        Atlas of the Rat Spinal Cord.
        in: The Spinal Cord. Academic Press, San Diego2009: 238-306
        • Zempoalteca R.
        • Martinez-Gomez M.
        • Hudson R.
        • Cruz Y.
        • Lucio R.A.
        An anatomical and electrophysiological study of the genitofemoral nerve and some of its targets in the male rat.
        J Anat. 2002; 201: 493-505
        • Zhu C.Z.
        • Nikkel A.L.
        • Martino B.
        • Bitner R.S.
        • Decker M.W.
        • Honore P.
        Dissociation between post-surgical pain behaviors and spinal Fos-like immunoreactivity in the rat.
        Eur J Pharmacol. 2006; 531: 108-117