Topical treatment with the opioid antagonist naltrexone facilitates closure of full-thickness wounds in diabetic rats

Experimental Biology and Medicine

Volumn 236, Issue 10, 2011, Pages 1122-1132

  McLaughlin, Patricia J ^a   Pothering, Christian A ^a   Immonen, Jessica A ^a   Zagon, Ian S ^a  

^a PENN STATE COLLEGE OF MEDICINE   (United States)

Author keywords

Diabetes; DNA synthesis; Naltrexone; Topical delivery; Wound healing

Indexed keywords

BROXURIDINE; NALTREXONE; OPIATE PEPTIDE; OPIATE RECEPTOR;

ANIMAL EXPERIMENT; ANIMAL MODEL; ARTICLE; CONTROLLED STUDY; DNA SYNTHESIS; FULL THICKNESS SKIN GRAFT; GENE OVEREXPRESSION; HISTOPATHOLOGY; INSULIN DEPENDENT DIABETES MELLITUS; MALE; NONHUMAN; PATHOPHYSIOLOGY; RAT; STREPTOZOCIN DIABETES; WOUND CLOSURE; WOUND CONTRACTION; WOUND HEALING IMPAIRMENT;

ADMINISTRATION, TOPICAL; ANIMALS; BLOOD GLUCOSE; DIABETES COMPLICATIONS; DIABETES MELLITUS, EXPERIMENTAL; DNA; MALE; NALTREXONE; NARCOTIC ANTAGONISTS; RATS; RATS, SPRAGUE-DAWLEY; SKIN; WOUND HEALING;

ANIMALIA; RATTUS;

EID: 80053460113     PISSN: 15353702     EISSN: 15353699     Source Type: Journal    
DOI: 10.1258/ebm.2011.011163     Document Type: Article

References (47)

1. Guo S, DiPietro LA. Factors affecting wound healing. J Dent Res 2010;89:219-29
2. Boulton JM, Vileikyte L, Ragnarson-Tennvall G, Apelquist J. The global burden of diabetic foot disease. Lancet 2005;366:1719-24
3. O'Loughlin A, McIntosh C, Dinneen SF, O'Brien T. Basic concepts to novel therapies: a review of the diabetic foot. Int J Lower Extremity Wounds 2010;9:90-102
4. Usui ML, Mansbridge JN, Carter WG, Fujita M, Olerud JE. Keratinocyte migration, proliferation, and differentiation in chronic ulcers from patients with diabetes and normal wounds. J Histochem Cytochem 2008;56:687-96
5. Akil J, Watson SJ, Young E, Lewis ME, Khachaturian H, Walker JM. Endogenous opioids: biology and function. Ann Rev Neurosci 1984;7:223-55
6. Zagon IS, Wu Y, McLaughlin PJ. The opioid growth factor, [Met5]-enkephalin, and the z (zeta) opioid receptor are present in human and mouse skin and tonically act to inhibit DNA synthesis in the epidermis. J Invest Dermatol 1996;106:490-7
7. Zagon IS, Jenkins JB, Sassani JW, Wylie JD, Ruth TB, Fry JL, Lang CM, McLaughlin PJ. Naltrexone, an opioid antagonist, facilitates re-epithelialization of the cornea in diabetic rat. Diabetes 2002;51:3055-62
8. Zagon IS, Essis FM, Verderame MF, Healy DA, Atnip RG, McLaughlin PJ. Opioid growth factor inhibits intimal hyperplasia in balloon-injured rat carotid artery. J Vasc Surg 2003;37:636-43
9. Blebea J, Mazo JE, Kihara TK, Vu J-H, McLaughlin PJ, Atnip RG, Zagon IS. Opioid growth factor modulates angiogenesis. J Vasc Surg 2000;32:364-73
10. Zagon IS, Donahue RN, Bonneau RH, McLaughlin PJ. B lymphocyte proliferation is suppressed by the opioid growth factor-opioid growth factor receptor axis: implication for the treatment of autoimmune diseases. Immunobiology 2011;216:173-83
11. Zagon IS, Donahue RN, Bonneau RH, McLaughlin PJ. T lymphocyte proliferation is suppressed by the opioid growth factor ([Met5]-enkephalin)-opioid growth factor receptor axis: implication for the treatment of autoimmune diseases. Immunobiology 2011;216:579-90
12. Wilson RP, McLaughlin PJ, Lang CM, Zagon IS. The opioid growth factor, [Met5]-enkephalin, inhibits DNA synthesis during recornification of mouse tail skin. Cell Prolif 2000;33:63-73
13. Fallucca F, Tonnarini G, Di Biase N, D'Alessandro M, Negri M. Plasma met-enkephalin levels in diabetic patients: influence of autonomic neuropathy. Metabolism 1996;45:1065-8
14. Negri M, Tonnarini G, D'Alessandro M, Fallucca F. Plasma met-enkephalin in type 1 diabetes. Metabolism 1992;41:460-1
15. Kolta MG, Pierzchala K, Houdi AA, Van Loon GR. Effect of diabetes on the levels of two forms of met-enkephalin in plasma and peripheral tissues of the rat. Neuropeptides 1992;21:55-63
16. Timmers K, Voyles NR, Zalenski C, Wilkins S, Recant L. Altered b-endorphin, met- and leu-enkephalins, and enkephalin-containing peptides in pancreas and pituitary of genetically obese diabetic (db/db) mice during development of diabetic syndrome. Diabetes 1986;35:1143-51
17. Greenberg J, Ellyin F, Pullen G, Ehrenpreis S, Singh SP, Cheng J. Methionine-enkephalin and b-endorphin levels in brain, pancreas, and adrenals of db/db mice. Endocrinology 1985;116:328-31
18. Klocek MS, Sassani JW, McLaughlin PJ, Zagon IS. Topically applied naltrexone restores corneal reepithelialization in diabetic rats. J Ocul Pharmacol Ther 2007;23:89-102
19. Zagon IS, Sassani JW, McLaughlin PJ. Reepithelialization of the human cornea is regulated by endogenous opioids. Invest Ophthalmol Vis Sci 2000;41:73-81
20. Cheng B, Liu H-W, Fu X-B, Sheng Z-Y, Li J-F. Coexistence and upregulation of three types of opioid receptors, mu, delta and kappa, in human hypertrophic scars. Clin Lab Invest 2008;158:713-20
21. Wintzen M, de Winter S, Out-Luiting JJ, van Duinen SG, Vermeer BJ. Presence of immunoreactive beta-endorphin in human skin. Exp Dermatol 2001;10:305-11
22. Tominaga M, Ogawa H, Takamori K. Possible roles of epidermal opioid systems in pruritus of atopic dermatitis. J Invest Dermatol 2007;127:2228-35
23. Bigliardi-Qi M, Gaveriaux-Ruff C, Zhou H, Hell C, Bady P, Rufli T, Kieffer B, Bigliardi PL. Deletion of d-opioid receptor in mice alters skin differentiation and delays wound healing. Differentiation 2006;74:174-185
24. Nissen JB, Kragballe K. Enkephalins modulate differentiation of normal human keratinocytes in vitro. Exp Dermatol 1997;6:222-9
25. Wenk HN, Honda CN. Immunohistochemical localization of delta opioid receptors in peripheral tissues. J Comp Neurol 1999;408:567-79
26. Salemi S, Aeschlimann A, Reisch N, Jungel A, Gay RE, Heppner FL, Michel BA, Gay S, Sprott H. Detection of kappa and delta opioid receptors in skin - outside the nervous system. Biochem Biophys Res Commun 2005;338:1012-7
27. Zagon IS, Rhodes RE, McLaughlin PJ. Localization of enkephalin immunoreactivity in diverse tissues and cells of the developing and adult rat. Cell Tissue Res 1986;246:561-5
28. Bigliardi PL, Bigliardi-Qi M, Buechner S, Rufli T. Expression of mu-opiate receptor in human epidermis and keratinocytes. J Invest Dermatol 1998;111:297-301
29. Kauser S, Schallreuter KU, Thody AJ, Gummer C, Tobin DJ. Regulation of human epidermal melanocyte biology by beta-endorphin. J Invest Dermatol 2003;120:1073-80
30. Havel PJ, Hahn TM, Sindelar DK, Baskin DG, Dallman MF, Weigle DS, Schwartz MW. Effects of streptozotocin-induced diabetes and insulin treatment on the hypothalamic melanocortin system and muscle uncoupling protein 3 expression in rats. Diabetes 2000;49:244-52
31. Pietramaggiori G, Scherer SS, Mathews JC, Gennaoui T, Lancerotto L, Ragno G, Valeri CR, Orgill DP. Quiescent platelets stimulate angiogenesis and diabetic wound repair. J Surg Res 2010;160:169-77
32. Yannas I. Tissue and Organ Regeneration in Adults. New York: Springer, 2001
33. Blumberg H, Dayton HB. Naloxone and related compounds. In: Kosterlitz HW, Collier HOJ, Villarreal JE, eds. Agonist and Antagonist Actions of Narcotic Analgesic Drugs. Baltimore: University Park Press, 1973:110-9
34. Sawynok J, Pinsky, LaBella FS. Minireview on the specificity of naloxone as an opiate antagonist. Life Sci 1979;25:1621-32
35. Wermeling DP, Banks SL, Hudson DA, Gill HS, Gupta J, Prausnitz MR, Stinchcomb AL. Microneedles permit transdermal delivery of a skin-impermeant medication to humans. Proc Natl Acad Sci USA 2008;105:2058-63
36. Stinchcomb AL, Swaan PW, Ekabo O, Harris KK, Brown J, Hammell DC, Cooperman TA, Pearsall M. Straight-chain naltrexone ester prodrugs: diffusion and concurrent esterase biotransformation in human skin. J Pharm Sci 2002;91:2571-8
37. Cheng F, McLaughlin PJ, Banks WA, Zagon IS. Passive diffusion of naltrexone into human and animal cells and upregulation of cell proliferation. Am J Physiol 2009;297:R844-52
38. Shih B, Garside E, McGrouther DA, Bayst A. Molecular dissection of abnormal wound healing processes resulting in keloid diseases. Wound Repair Regener 2010;18:139-53
39. Mustoe T. Understanding chronic wounds: a unifying hypothesis on their pathogenesis and implications for therapy. Am J Surg 2004;187:655-705
40. Brem H, Balledux J, Bloom T, Herstein MD, Hollier L. Healing of diabetic foot ulcers and pressure ulcers with human skin equivalent: a new paradigm in wound healing. Arch Surg 2000;135:627-34
41. Leslie FM. Methods used for the study of opioid receptors. Pharmacol Rev 1987;39:197-249
42. Zagon IS, Verderame MF, McLaughlin PJ. The biology of the opioid growth factor receptor (OGFr). Brain Res Rev 2002;38:351-76
43. Cheng F, McLaughlin PJ, Verderame MF, Zagon IS. The OGF-OGFr axis utilizes the p16INK4a and p21WAF1/CIP1 pathways to restrict normal cell proliferation. Mol Biol Cell 2009;20:319-27
44. Zagon IS, Sassani JW, McLaughlin PJ. Opioid growth factor modulates corneal epithelial growth in tissue culture. Am J Physiol 1995;268:R942-50
45. Klocek MS, Sassani JW, McLaughlin PJ, Zagon IS. Topically applied naltrexone restores corneal reepithelialization in diabetic rats. J Ocul Pharmacol Therap 2007;23:89-102
46. Kirchmayer U, Davoli M, Verster AD, Amato L, Ferri A, Perucci CA. A systematic review on the efficacy of naltrexone maintenance treatment in opioid dependence. Addiction 2002;97:1241-9
47. Swift R. Emerging approaches to managing alcohol dependence. Am J Health Syst Pharm 2007;64:S12-S22