Incision-induced Pain Behaviors in the DBA/2 Mouse

DBA/2 계열 마우스의 절개통증에서의 행동양상

  • Bae, Da Hyoun (Department of Anesthesiology and Pain Medicine, Our Lady of Mercy Hospital, The Catholic University College of Medicine) ;
  • Park, Soo Seog (Department of Anesthesiology and Pain Medicine, Our Lady of Mercy Hospital, The Catholic University College of Medicine) ;
  • Woo, Young Cheol (Department of Anesthesiology and Pain Medicine, Joong Ang University College of Medicine)
  • 배다현 (가톨릭대학교 의과대학 성모자애병원 마취통증의학교실) ;
  • 박수석 (가톨릭대학교 의과대학 성모자애병원 마취통증의학교실) ;
  • 우영철 (중앙대학교 의과대학 마취통증의학교실)
  • Received : 2008.01.24
  • Accepted : 2008.02.27
  • Published : 2008.06.01

Abstract

Background: Because genetic manipulation is commonly accomplished in mice, mouse models for pain have advanced our understanding of the mechanisms of persistent pain. The purpose of this experimental study is to develop a mouse model for understanding incision induced postoperative pain. Methods: A longitudinal incision was made at the hindpaw of male DBA/2 mice. The withdrawal frequency(WF) from applications of von Frey filaments and the response frequency (RF) to blunt mechanical stimulation were examined in an incision group and a control grouP. The withdrawal latency (WL) to radiant heat and a pain score based on weight bearing were also measured. Tests were performed 1 day before incision, and 2 hours, 1-3 days, 5 days and 7 days after incision. Results: The WF for the strongest filament was $35.0{\pm}9.1%$ before incision and this increased to $100.0{\pm}0%$ at 2 hours and to $65.0{\pm}9.1%$ at 7 days after incision. The RF to the blunt stimulus was $4.1{\pm}4.1%$ before incision and $100.0{\pm}0.0%$ at 2 hours and $42.8{\pm}10.8%$ at 7 days after incision. The WL was $6.6{\pm}0.5sec$ before incision and $2.4{\pm}0.3sec$ at 2 hours and $5.9{\pm}0.6sec$ at 7 days after incision. The pain score increased from $1.1{\pm}0.8$ to $7.4{\pm}1.5$ at 2 days after incision. Conclusions: A mouse model of acute postoperative pain was developing by making a surgical incision in the mouse hindpaw. Mechanical hyperalgesia and allodynia lasting for several days demonstrate that this model has similarities to the human post-operative pain state. Future studies will allow us to further investigate the genetic and molecular mechanisms of incisional pain.

Keywords

References

  1. Woolf CJ, Chong MS: Preemptive analgesia-treating postoperative pain by preventing the establishment of central sensitization. Anesth Analg 1993; 77: 362-79 https://doi.org/10.1213/00000539-199377020-00026
  2. Kehlet H: Postoperative pain relief-what is the issue? Br J Anaesth 1994; 72: 375-8 https://doi.org/10.1093/bja/72.4.375
  3. Brennan TJ, Vandermeulen EP, Gebhart GF: Characterization of a rat model of incisional pain. Pain 1996; 64: 493-501 https://doi.org/10.1016/0304-3959(95)01441-1
  4. Tverskoy M, Cozacov C, Ayache M, Bradley EL Jr, Kissin I: Postoperative pain after inguinal herniorrhaphy with different types of anesthesia. Anesth Analg 1990; 70: 29-35 https://doi.org/10.1213/00000539-199002001-00029
  5. Schulze S, Roikjaer O, Hasselstrom L, Jensen NH, Kehlet H: Epidural bupivacaine and morphine plus systemic indomethacin eliminates pain but not systemic response and convalescence after cholecystectomy. Surgery 1988; 103: 321-7
  6. Johansson B, Glise H, Hallerback B, Dalman P, Kristoffersson A: Preoperative local infiltration with ropivacaine for postoperative pain relief after cholecystectomy. Anesth Analg 1994; 78: 210-4 https://doi.org/10.1213/00000539-199402000-00003
  7. Tverskoy M, Oz Y, Isakson A, Finger J, Bradley EL Jr, Kissin I: Preemptive effect of fentanyl and ketamine on postoperative pain and wound hyperalgesia. Anesth Analg 1994; 78: 205-9 https://doi.org/10.1213/00000539-199402000-00002
  8. Inagaki Y, Mashimo T, Yoshiya I: Time-related differential effects of epidural morphine on the neuraxis. Anesth Analg 1993; 76: 308-15
  9. Tjolsen A, Berge OG, Hunskaar S, Rosland JH, Hole K: The formalin test: an evaluation of the method. Pain 1992; 51: 5-17 https://doi.org/10.1016/0304-3959(92)90003-T
  10. Kim SH, Chung JM: An experimental model for peripheral neuropathy produced by segmental spinal nerve ligation in the rat. Pain 1992; 50: 355-63 https://doi.org/10.1016/0304-3959(92)90041-9
  11. Mogil JS: The genetic mediation of individual differences in sensitivity to pain and its inhibition. Proc Natl Acad Sci USA 1999; 96: 7744-51
  12. Kelly DD: The role of endorphins in stress-induced analgesia. Ann N Y Acad Sci 1982; 398: 260-71 https://doi.org/10.1111/j.1749-6632.1982.tb39499.x
  13. Smolensky MH, Halberg F, Harter J, Hsi B, Nelson W: Higher corticosterone values at a fixed single timepoint in serum from mice "trained" by prior handling. Chronobiologia 1978; 5: 1-13
  14. Hole K, Tjolsen A: The tail-flick and formalin tests in rodents: changes in skin temperature as a confounding factor. Pain 1993; 53: 247-54 https://doi.org/10.1016/0304-3959(93)90220-J
  15. Mogensen T, Eliasen K, Ejlersen E, Vegger P, Nielsen IK, Kehlet H: Epidural clonidine enhances postoperative analgesia from a combined low-dose epidural bupivacaine and morphine regimen. Anesth Analg 1992; 75: 607-10
  16. Richmond CE, Bromley LM, Woolf CJ: Preoperative morphine pre-empts postoperative pain. Lancet 1993; 342: 73-5 https://doi.org/10.1016/0140-6736(93)91284-S
  17. Kim SH, Na HS, Sheen K, Chung JM: Effects of sympathectomy on a rat model of peripheral neuropathy. Pain 1993; 55: 85-92 https://doi.org/10.1016/0304-3959(93)90187-T
  18. Lewin GR, Ritter AM, Mendell LM: Nerve growth factor-induced hyperalgesia in the neonatal and adult rat. J Neurosci 1993; 13: 2136-48 https://doi.org/10.1523/JNEUROSCI.13-05-02136.1993
  19. Ren K, Dubner R: NMDA receptor antagonists attenuate mechanical hyperalgesia in rats with unilateral inflammation of the hindpaw. Neurosci Lett 1993; 163: 22-6 https://doi.org/10.1016/0304-3940(93)90220-F
  20. Tal M, Bennett GJ: Extra-territorial pain in rats with a peripheral mononeuropathy: mechano-hyperalgesia and mechano-allodynia in the territory of an uninjured nerve. Pain 1994; 57: 375-82 https://doi.org/10.1016/0304-3959(94)90013-2
  21. Dahl JB, Brennum J, Arendt-Nielsen L, Jensen TS, Kehlet H: The effect of pre-versus postinjury infiltration with lidocaine on thermal and mechanical hyperalgesia after heat injury to the skin. Pain 1993; 53: 43-51 https://doi.org/10.1016/0304-3959(93)90054-S
  22. Brennum J, Dahl JB, Moiniche S, Arendt Nielsen L: Quantitative sensory examination of epidural anaesthesia and analgesia in man: effects of pre- and post-traumatic morphine on hyperalgesia. Pain 1994; 59: 261-71 https://doi.org/10.1016/0304-3959(94)90079-5
  23. Carter RB: Differentiating analgesic and non-analgesic drug activities on rat hot plate: effect of behavioral endpoint. Pain 1991; 47: 211-20 https://doi.org/10.1016/0304-3959(91)90207-E
  24. Espejo EF, Mir D: Structure of the rat's behaviour in the hot plate test. Behav Brain Res 1993; 56: 171-6 https://doi.org/10.1016/0166-4328(93)90035-O
  25. Yanai K, Son LZ, Endou M, Sakurai E, Nakagawasai O, Tadano T, et al: Behavioural characterization and amounts of brain monoamines and their metabolites in mice lacking histamine H1 receptors. Neuroscience 1998; 87: 479-87 https://doi.org/10.1016/S0306-4522(98)00167-5
  26. Cao YQ, Mantyh PW, Carlson EJ, Gillespie AM, Epstein CJ, Basbaum AI: Primary afferent tachykinins are required to experience moderate to intense pain. Nature 1998; 392: 390-4 https://doi.org/10.1038/32897
  27. Caterina MJ, Leffler A, Malmberg AB, Martin WJ, Trafton J, Petersen-Zeitz KR, et al: Impaired nociception and pain sensation in mice lacking the capsaicin receptor. Science 2000; 288: 306-13 https://doi.org/10.1126/science.288.5464.306
  28. Wilson SG, Mogil JS: Measuring pain in the (knockout) mouse: big challenges in a small mammal. Behav Brain Res 2001; 125: 65-73 https://doi.org/10.1016/S0166-4328(01)00281-9
  29. Cook AJ, Woolf CJ, Wall PD, McMahon SB: Dynamic receptive field plasticity in rat spinal cord dorsal horn following C-primary afferent input. Nature 1987; 325: 151-3 https://doi.org/10.1038/325151a0