DOI QR코드

DOI QR Code

Diverse characters of Brennan's paw incision model regarding certain parameters in the rat

  • Kumar, Rahul (Department of Anatomy, All India Institute of Medical Sciences) ;
  • Gupta, Shivani (Department of Anatomy, All India Institute of Medical Sciences) ;
  • Gautam, Mayank (Department of Anatomy, All India Institute of Medical Sciences) ;
  • Jhajhria, Saroj Kaler (Department of Anatomy, All India Institute of Medical Sciences) ;
  • Ray, Subrata Basu (Department of Anatomy, All India Institute of Medical Sciences)
  • Received : 2018.12.27
  • Accepted : 2019.03.12
  • Published : 2019.07.01

Abstract

Background: Brennan's rodent paw incision model has been extensively used for understanding mechanisms underlying postoperative pain in humans. However, alterations of physiological parameters like blood pressure and heart rate, or even feeding and drinking patterns after the incision have not been documented as yet. Moreover, though eicosanoids like prostaglandins and leukotrienes contribute to inflammation, tissue levels of these inflammatory mediators have never been studied. This work further investigates the antinociceptive effect of protein C after intra-wound administration. Methods: Separate groups of Sprague-Dawley rats were used for quantitation of cyclooxygenase (COX) activity and leukotriene B4 level by enzyme-linked immunosorbent assay, as well as estimation of cardiovascular parameters and feeding and drinking behavior after paw incision. In the next part, rats were subjected to incision and $10{\mu}g$ of protein C was locally administered by a micropipette. Both evoked and non-evoked pain parameters were then estimated. Results: COX, particularly COX-2 activity and leukotriene B4 levels increased after incision. Hemodynamic parameters were normal. Feeding and drinking were affected on days 1 and 3, and on day 1, respectively. Protein C attenuated non-evoked pain behavior alone up to day 2. Conclusions: Based upon current observations, Brennan's rodent paw incision model appears to exhibit a prolonged period of nociception similar to that after surgery, with minimal interference of physiological parameters. Protein C, which is likely converted to activated protein C in the wound, attenuated the guarding score, which probably represents pain at rest after surgery in humans.

Keywords

References

  1. Kumar V, Abbas AK, Aster JC. Robbins basic pathology. Philadelphia, Elsevier. 2013, pp 29-73.
  2. Dubois RN, Abramson SB, Crofford L, Gupta RA, Simon LS, Van De Putte LB, et al. Cyclooxygenase in biology and disease. FASEB J 1998; 12: 1063-73. https://doi.org/10.1096/fasebj.12.12.1063
  3. Funk CD. Prostaglandins and leukotrienes: advances in eicosanoid biology. Science 2001; 294: 1871-5. https://doi.org/10.1126/science.294.5548.1871
  4. Xu J, Brennan TJ. The pathophysiology of acute pain: animal models. Curr Opin Anaesthesiol 2011; 24: 508-14. https://doi.org/10.1097/ACO.0b013e32834a50d8
  5. Wu C, Boustany L, Liang H, Brennan TJ. Nerve growth factor expression after plantar incision in the rat. Anesthesiology 2007; 107: 128-35. https://doi.org/10.1097/01.anes.0000267512.08619.bd
  6. Kim TJ, Freml L, Park SS, Brennan TJ. Lactate concentrations in incisions indicate ischemic-like conditions may contribute to postoperative pain. J Pain 2007; 8: 59-66. https://doi.org/10.1016/j.jpain.2006.06.003
  7. Gautam M, Prasoon P, Kumar R, Reeta KH, Kaler S, Ray SB. Role of neurokinin type 1 receptor in nociception at the periphery and the spinal level in the rat. Spinal Cord 2016; 54: 172-82. https://doi.org/10.1038/sc.2015.206
  8. Foster D, Dav ie EW. Characterization of a cDNA coding for human protein C. Proc Natl Acad Sci U S A 1984; 81: 4766-70. https://doi.org/10.1073/pnas.81.15.4766
  9. Joyce DE, Gelbert L, Ciaccia A, DeHoff B, Grinnell BW. Gene expression profile of antithrombotic protein c defines new mechanisms modulating inflammation and apoptosis. J Biol Chem 2001; 276: 11199-203. https://doi.org/10.1074/jbc.C100017200
  10. Kumar R, Prasoon P, Gautam M, Ray SB. Comparative antinociceptive effect of arachidonylcyclopropylamide, a cannabinoid 1 receptor agonist & lignocaine, a local anaesthetic agent, following direct intrawound administration in rats. Indian J Med Res 2016; 144: 730-40. https://doi.org/10.4103/ijmr.IJMR_1402_15
  11. Bauer KA, Kass BL, Beeler DL, Rosenberg RD. Detection of protein C activation in humans. J Clin Invest 1984; 74: 2033-41. https://doi.org/10.1172/JCI111626
  12. Long GL, Belagaje RM, MacGillivray RT. Cloning and sequencing of liver cDNA coding for bovine protein C. Proc Natl Acad Sci U S A 1984; 81: 5653-6. https://doi.org/10.1073/pnas.81.18.5653
  13. Esmon CT. The endothelial cell protein C receptor. Thromb Haemost 2000; 83: 639-43. https://doi.org/10.1055/s-0037-1613883
  14. Marlar RA, Kleiss AJ, Griffin JH. Mechanism of action of human activated protein C, a thrombin-dependent anticoagulant enzyme. Blood 1982; 59: 1067-72. https://doi.org/10.1182/blood.V59.5.1067.1067
  15. Wijewardena A, Lajevardi SS, Vandervord E, Vandervord J, Lang TC, Fulcher G , et al. Activated protein C to heal pressure ulcers. Int Wound J 2016; 13: 986-91. https://doi.org/10.1111/iwj.12343
  16. Xue M, Thompson P, Kelso I, Jackson C. Activated protein C stimulates proliferation, migration and wound closure, inhibits apoptosis and upregulates MMP-2 activity in cultured human keratinocytes. Exp Cell Res 2004; 299: 119-27. https://doi.org/10.1016/j.yexcr.2004.05.015
  17. Bernard GR, Vincent JL, Laterre PF, LaRosa SP, Dhainaut JF, Lopez-Rodriguez A, et al. Efficacy and safety of recombinant human activated protein C for severe sepsis. N Engl J Med 2001; 344: 699-709. https://doi.org/10.1056/NEJM200103083441001
  18. Yuksel M, Okajima K, Uchiba M, Horiuchi S, Okabe H. Activated protein C inhibits lipopolysaccharide-induced tumor necrosis factor-alpha production by inhibiting activation of both nuclear factor-kappa Band activator protein-1 in human monocytes. Thromb Haemost 2002; 88: 267-73. https://doi.org/10.1055/s-0037-1613197
  19. Xue M, March L, Sambrook PN, Jackson CJ. Differential regulation of matrix metalloproteinase 2 and matrix metalloproteinase 9 by activated protein C : relevance to inflammation in rheumatoid arthritis. Arthritis Rheum 2007; 56: 2864-74. https://doi.org/10.1002/art.22844
  20. Smith JR, Galie PA, Slochower DR, Weisshaar CL, Janmey PA, Winkelstein BA. Salmon-derived thrombin inhibits development of chronic pain through an endothelial barrier protective mechanism dependent on APC. Biomaterials 2016; 80: 96-105. https://doi.org/10.1016/j.biomaterials.2015.11.062
  21. Pichler L, Schramm W, Ulrich W, Varadi K, Schwarz HP. Antinociceptive properties of protein C in a model of inflammatory hyperalgesia in rats. Thromb Haemost 1995; 73: 252-5. https://doi.org/10.1055/s-0038-1653760
  22. Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain 1983; 16: 109-10. https://doi.org/10.1016/0304-3959(83)90201-4
  23. 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
  24. Brown C, McFarlane-Anderson N, Alexander-Lindo R, Bishop K, Dasgupta T, McGrowder D. The effects of S-nitrosoglutathione and S-nitroso-N-acetyl-D, L-penicillamine in a rat model of pre-eclampsia. J Nat Sci Biol Med 2013; 4: 330-5. https://doi.org/10.4103/0976-9668.116998
  25. Wang Y, Cong Y, Li J, Li X, Li B, Qi S. Comparison of invasive blood pressure measurements from the caudal ventral artery and the femoral artery in male adult SD and Wistar rats. PLoS One 2013; 8: e60625. https://doi.org/10.1371/journal.pone.0060625
  26. Spofford CM, Ashmawi H, Subieta A, Buev ich F, Moses A, Baker M, et al. Ketoprofen produces modality-specific inhibition of pain behaviors in rats after plantar incision. Anesth Analg 2009; 109: 1992-9. https://doi.org/10.1213/ANE.0b013e3181bbd9a3
  27. Chaplan SR, Bach FW, Pogrel JW, Chung JM, Yaksh TL. Quantitative assessment of tactile allodynia in the rat paw. J Neurosci Methods 1994; 53: 55-63. https://doi.org/10.1016/0165-0270(94)90144-9
  28. Hargreaves K, Dubner R, Brown F, Flores C, Joris J. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988; 32: 77-88. https://doi.org/10.1016/0304-3959(88)90026-7
  29. Pogatzki-Zahn EM, Segelcke D, Schug SA. Postoperative pain-from mechanisms to treatment. Pain Rep 2017; 2: e588. https://doi.org/10.1097/PR9.0000000000000588
  30. Braz JM, Etlin A, Juarez-Salinas D, Llewellyn-Smith IJ, Basbaum AI. Rebuilding CNS inhibitory circuits to control chronic neuropathic pain and itch. Prog Brain Res 2017; 231: 87-105. https://doi.org/10.1016/bs.pbr.2016.10.001
  31. Lavand'homme P, Wu C, Katz J. From acute to chronic postoperative pain. In: Pain 2018: refresher courses for the 17th World Congress on Pain. Edited by Gold MS, Pogatzki-Zahn EM, Wallace MS. Washington, IASP Press. 2018, pp 147-57.
  32. Polanco-Garcia M, Garcia-Lopez J, Fabregas N, Meissner W, Puig MM; PAIN-OUT-Spain Consortium. Postoperative pain management in Spanish hospitals: a cohort study using the pain-out registry. J Pain 2017; 18: 1237-52. https://doi.org/10.1016/j.jpain.2017.05.006
  33. Brennan TJ. Pathophysiology of postoperative pain. Pain 2011; 152(3 Suppl): S33-40. https://doi.org/10.1016/j.pain.2010.11.005
  34. Rouzer CA, Marnett LJ. Cyclooxygenases: structural and functional insights. J Lipid Res 2009; 50 Suppl: S29-34. https://doi.org/10.1194/jlr.R800042-JLR200
  35. Smith WL, DeWitt DL, Garavito RM. Cyclooxygenases: structural, cellular, and molecular biology. Annu Rev Biochem 2000; 69: 145-82. https://doi.org/10.1146/annurev.biochem.69.1.145
  36. Futagami A, Ishizaki M, Fukuda Y, Kawana S, Yamanaka N. Wound healing involves induction of cyclooxygenase-2 expression in rat skin. Lab Invest 2002; 82: 1503-13. https://doi.org/10.1097/01.LAB.0000035024.75914.39
  37. Koller M, Konig W, Brom J, Raulf M, Gross-Weege W, Erbs G, et al. Generation of leukotrienes from human polymorphonuclear granulocytes of severely burned patients. J Trauma 1988; 28: 733-40. https://doi.org/10.1097/00005373-198806000-00002
  38. Cunha JM, Sachs D, Canetti CA, Poole S, Ferreira SH, Cunha FQ. The critical role of leukotriene B4 in antigen-induced mechanical hyperalgesia in immunised rats. Br J Pharmacol 2003; 139: 1135-45. https://doi.org/10.1038/sj.bjp.0705346
  39. Guimaraes FR, Sales-Campos H, Nardini V, da Costa TA, Fonseca MTC, Junior VR, et al. The inhibition of 5-Lipoxygenase (5-LO) products leukotriene B4 ($LTB_4$) and cysteinyl leukotrienes (cysLTs) modulates the inflammatory response and improves cutaneous wound healing. Clin Immunol 2018; 190: 74-83. https://doi.org/10.1016/j.clim.2017.08.022
  40. Foo H, Crabtree K, Thrasher A, Mason P. Eating is a protected behav ior even in the face of persistent pain in male rats. Physiol Behav 2009; 97: 426-9. https://doi.org/10.1016/j.physbeh.2009.03.015
  41. Hackett AF, Yeung CK, Hill GL. Eating patterns in patients recovering from major surgery--a study of voluntary food intake and energy balance. Br J Surg 1979; 66: 415-8. https://doi.org/10.1002/bjs.1800660613
  42. Fujita M, Fukuda T, Sato Y, Takasusuki T, Tanaka M. Allopregnanolone suppresses mechanical allodynia and internalization of neurokinin-1 receptors at the spinal dorsal horn in a rat postoperative pain model. Korean J Pain 2018; 31: 10-5. https://doi.org/10.3344/kjp.2018.31.1.10
  43. Deane R, LaRue B, Sagare AP, Castellino FJ, Zhong Z, Zlokovic BV. Endothelial protein Creceptor-assisted transport of activated protein Cacross the mouse blood-brain barrier. J Cereb Blood Flow Metab 2009; 29: 25-33. https://doi.org/10.1038/jcbfm.2008.117
  44. Carney EF. Inflammation: activated protein C inhibits inflammasome activation in IRI. Nat Rev Nephrol 2017; 13: 662. https://doi.org/10.1038/nrneph.2017.139
  45. Riewald M, Petrovan RJ, Donner A, Ruf W. Activated protein C signals through the thrombin receptor PAR1 in endothelial cells. J Endotoxin Res 2003; 9: 317-21. https://doi.org/10.1177/09680519030090050801
  46. Toltl LJ, Austin RC, Liaw PC. Activated protein C modulates inflammation, apoptosis and tissue factor procoagulant activity by regulating endoplasmic reticulum calcium depletion in blood monocytes. J Thromb Haemost 2011; 9: 582-92. https://doi.org/10.1111/j.1538-7836.2010.04177.x
  47. Comp PC, Nixon RR, Esmon CT. Determination of functional levels of protein C, an antithrombotic protein, using thrombinthrombomodulin complex. Blood 1984; 63: 15-21. https://doi.org/10.1182/blood.V63.1.15.15

Cited by

  1. A novel excisional wound pain model for evaluation of analgesics in rats vol.34, pp.2, 2019, https://doi.org/10.3344/kjp.2021.34.2.165