Morphine for the treatment of pain in sickle cell disease

Scientific World Journal

Volumn 2015, Issue , 2015, Pages

  Gupta, Mihir ^a   Msambichaka, Lilian ^b,c   Ballas, Samir K ^d   Gupta, Kalpna ^b  

^a STANFORD UNIVERSITY SCHOOL OF MEDICINE   (United States)

^b UNIVERSITY OF MINNESOTA MEDICAL SCHOOL   (United States)

^c CHRISTIANA CARE HEALTH SYSTEM   (United States)

^d THOMAS JEFFERSON UNIVERSITY HOSPITAL   (United States)

Author keywords

[No Author keywords available]

Indexed keywords

MORPHINE; OPIATE; OPIATE RECEPTOR; TOLL LIKE RECEPTOR 4; NARCOTIC ANALGESIC AGENT;

ANALGESIA; DRUG EXPOSURE; ERYTHROCYTE; HUMAN; KIDNEY DISEASE; LEG ULCER; LUNG DISEASE; NONHUMAN; ORGAN SYSTEMS; PAIN; PATHOPHYSIOLOGY; PULMONARY HYPERTENSION; REVIEW; SICKLE CELL ANEMIA; COMPLICATION; PROCEDURES;

ANALGESICS, OPIOID; ANEMIA, SICKLE CELL; HUMANS; MORPHINE; PAIN; PAIN MANAGEMENT;

EID: 84947649714     PISSN: 23566140     EISSN: 1537744X     Source Type: Journal    
DOI: 10.1155/2015/540154     Document Type: Review

References (110)

1. F.B.Piel, S. I. Hay, S. Gupta, D. J.Weatherall, andT. N.Williams, "Global burden of sickle cell anaemia in children under five, 2010-2050:modelling based on demographics, excessmortality, and interventions" PLoS Medicine, vol. 10, no. 7, Article ID e1001484, 2013.
2. S. K. Ballas, K. Gupta, and P. Adams-Graves, "Sickle cell pain: a critical reappraisal" Blood, vol. 120, no. 18, pp. 3647-3656, 2012.
3. D. Fletcher and V. Martinez, "Opioid-induced hyperalgesia in patients after surgery: a systematic review and a meta-analysis" British Journal of Anaesthesia, vol. 112, no. 6, pp. 991-1004, 2014.
4. S. H. Kim, N. Stoicea, S. Soghomonyan, and S. D. Bergese, "Intraoperative use of remifentanil and opioid induced hyperalgesia/acute opioid tolerance: systematic review" Frontiers in Pharmacology, vol. 5, article 108, 2014.
5. D.G. Soergel, R. A. Subach, N. Burnham et al., "Biased agonism of the μ-opioid receptor by TRV130 increases analgesia and reduces on-target adverse effects versus morphine: a randomized, double-blind, placebo-controlled, crossover study in healthy volunteers" Pain, vol. 155, no. 9, pp. 1829-1835, 2014.
6. K. Gupta, S. Kshirsagar, L. Chang et al., "Morphine stimulates angiogenesis by activating proangiogenic and survivalpromoting signaling and promotes breast tumor growth" Cancer Research, vol. 62, no. 15, pp. 4491-4498, 2002.
7. I. D. Buchanan, M. Woodward, and G. W. Reed, "Opioid selection during sickle cell pain crisis and its impact on the development of acute chest syndrome" Pediatric Blood and Cancer, vol. 45, no. 5, pp. 716-724, 2005.
8. L. Spikes, P.Dalvi,O. Tawfik et al., "Enhanced pulmonary arteriopathy in simian immunodeficiency virus-infected macaques exposed tomorphine"The American Journal of Respiratory and Critical Care Medicine, vol. 185, no. 11, pp. 1235-1243, 2012.
9. M. L. Weber, M. Farooqui, J. Nguyen et al., "Morphine induces mesangial cell proliferation and glomerulopathy via κ-opioid receptors" American Journal of Physiology: Renal Physiology, vol. 294, no. 6, pp. F1388-F1397, 2008.
10. X. Lan, P. Rai, N. Chandel et al., "Morphine induces albuminuria by compromising podocyte integrity" PLoSONE, vol. 8, no. 3, Article ID e55748, 2013.
11. D. Zylla, B. L. Gourley, D. Vang et al., "Opioid requirement, opioid receptor expression, and clinical outcomes in patients with advanced prostate cancer" Cancer, vol. 119, no. 23, pp. 4103-4110, 2013.
12. D. Zylla,M.A.Kuskowski,K.Gupta, and P.Gupta, "Association of opioid requirement and cancer pain with survival in advanced non-small cell lung cancer" British Journal of Anaesthesia. In press.
13. E. E. Cunningham, M. A. Zielezny, and R. C. Venuto, "Heroinassociated nephropathy. A nationwide problem" Journal of the American Medical Association, vol. 250, no. 21, pp. 2935-2936, 1983.
14. D. C. Rees, T. N. Williams, and M. T. Gladwin, "Sickle-cell disease" The Lancet, vol. 376, no. 9757, pp. 2018-2031, 2010.
15. O. S. Platt, D. J. Brambilla,W. F.Rosse et al., "Mortality in sickle cell disease. Life expectancy and risk factors for early death"The NewEngland Journal ofMedicine, vol. 330, no.23, pp. 1639-1644, 1994.
16. C.D.Dampier,W. R. Smith, C. G.Wager et al., "IMPROVE trial: a randomized controlled trial of patient-controlled analgesia for sickle cell painful episodes: rationale, design challenges, initial experience, and recommendations for future studies" Clinical Trials, vol. 10, no. 2, pp. 319-331, 2013.
17. "Evidence based management of sickle cell disease" Expert Panel Report, 2014, http://www.nhlbi.nih.gov/health-pro/guidelines/sickle-cell-disease-guidelines.
18. S. K. Ballas, Sickle Cell Pain, IASP Press,Washington, DC, USA, 2014.
19. D. S.Darbari, M.Neely, J. van den Anker, and S. Rana, "Increased clearance of morphine in sickle cell disease: implications for pain management" Journal of Pain, vol. 12, no. 5, pp. 531-538, 2011.
20. C. D. Dampier, B. N. Y. Setty, J. Logan, J. G. Ioli, and R. Dean, "Intravenous morphine pharmacokinetics in pediatric patients with sickle cell disease" Journal of Pediatrics, vol. 126, no. 3, pp. 461-647, 1995.
21. D. R. Kohli, Y. Li, S. G. Khasabov et al., "Pain-related behaviors and neurochemical alterations in mice expressing sickle hemoglobin: modulation by cannabinoids" Blood, vol. 116, no. 3, pp. 456-465, 2010.
22. C. A. Hillery, P. C. Kerstein, D. Vilceanu et al., "Transient receptor potential vanilloid 1 mediates pain in mice with severe sickle cell disease" Blood, vol. 118, no. 12, pp. 3376-3383, 2011.
23. D. M. Cain, D. Vang, D. A. Simone, R. P. Hebbel, and K. Gupta, "Mouse models for studying pain in sickle disease: effects of strain, age, and acuteness" British Journal of Haematology, vol. 156, no. 4, pp. 535-544, 2012.
24. L. Vincent, D. Vang, J. Nguyen et al., "Mast cell activation contributes to sickle cell pathobiology and pain in mice." Blood, vol. 122, no. 11, pp. 1853-1862, 2013.
25. J. Close and R. Lottenberg, "Effectiveness of imatinib therapy for a patient with sickle cell anemia and chronic myelocytic leukemia" in Proceedings of the 51st ASH Annual Meeting and Exposition, New Orleans, La, USA, 2009.
26. K. Stankovic Stojanovic, B. Thioliere, E. Garandeau, I. Lecomte, C. Bachmeyer, and F. Lionnet, "Chronic myeloid leukaemia and sickle cell disease: could imatinib prevent vaso-occlusive crisis?" British Journal of Haematology, vol. 155, no. 2, pp. 271-272, 2011.
27. O. J. Biedrzycki, D. Bevan, and S. Lucas, "Fatal overdose due to prescription fentanyl patches in a patient with sickle cell/-thalassemia and acute chest syndrome: a case report and review of the literature"The American Journal of ForensicMedicine and Pathology, vol. 30, no. 2, pp. 188-190, 2009.
28. U.Boerner, S.Abbott, andR.L.Roe,"Themetabolismofmorphine and heroin in man" Drug Metabolism Reviews, vol. 4, no. 1, pp. 39-73, 1975.
29. S. Y. Yeh, "Urinary excretion of morphine and its metabolites in morphine dependent subjects" Journal of Pharmacology and Experimental Therapeutics, vol. 192, no. 1, pp. 201-210, 1975.
30. F. Stain-Texier, P. Sandouk, and J.-M. Scherrmann, "Intestinal absorption and stability of morphine 6-glucuronide in different physiological compartments of the rat" Drug Metabolism and Disposition, vol. 26, no. 5, pp. 383-387, 1998.
31. A. Bodenham, K. Quinn, and G. R. Park, "Extrahepatic morphine metabolism in man during the anhepatic phase of orthotopic liver transplantation" British Journal of Anaesthesia, vol. 63, no. 4, pp. 380-384, 1989.
32. M. Waldhoer, S. E. Bartlett, and J. L. Whistler, "Opioid receptors" Annual Review of Biochemistry, vol. 73, pp. 953-990, 2004.
33. J. L. Whistler, H.-H. Chuang, P. Chu, L. Y. Jan, and M. Von Zastrow, "Functional dissociation of μ opioid receptor signaling and endocytosis: implications for the biology of opiate tolerance and addiction" Neuron, vol. 23, no. 4, pp. 737-746, 1999.
34. C. Sternini, M. Spann, B. Anton et al., "Agonist-selective endocytosis of μ opioid receptor by neurons in vivo" Proceedings of the National Academy of Sciences of the United States of America, vol. 93, no. 17, pp. 9241-9246, 1996.
35. L.He, J. Fong,M. von Zastrow, and J. L.Whistler, "Regulation of opioid receptor trafficking and morphine tolerance by receptor oligomerization" Cell, vol. 108, no. 2, pp. 271-282, 2002.
36. K. Gupta and E. Stephenson, The Endothelium: A Comprehensive Reference, Cambridge University Press, New York, NY, USA, 2007.
37. H.Wen, Y. Lu, H. Yao, and S. Buch, "Morphine induces expression of platelet-derived growth factor in human brain microvascular endothelial cells: implication for vascular permeability" PLoS ONE, vol. 6, no. 6,Article ID e21707, 2011.
38. K. Luk, S. Boatman, K. N. Johnson et al., "Influence ofmorphine on pericyte-endothelial interaction: implications for antiangiogenic therapy" Journal of Oncology, vol. 2012,Article ID458385, 10 pages, 2012.
39. P. A. Singleton, L. Moreno-Vinasco, S. Sammani, S. L. Wanderling, J. Moss, and J. G. N. Garcia, "Attenuation of vascular permeability by methylnaltrexone: role of mOP-R and S1P3 transactivation" The American Journal of Respiratory Cell and Molecular Biology, vol. 37, no. 2, pp. 222-231, 2007.
40. P. A. Singleton,M.W. Lingen, M. J. Fekete, J.G.N.Garcia, and J. Moss, "Methylnaltrexone inhibits opiate and VEGF-induced angiogenesis: role of receptor transactivation" Microvascular Research, vol. 72, no. 1-2, pp. 3-11, 2006.
41. C. Chen, M. Farooqui, and K. Gupta, "Morphine stimulates vascular endothelial growth factor-like signaling in mouse retinal endothelial cells" Current Neurovascular Research, vol. 3, no. 3, pp. 171-180, 2006.
42. M. Farooqui, Y. Li, T. Rogers et al., "COX-2 inhibitor celecoxib prevents chronic morphine-induced promotion of angiogenesis, tumour growth, metastasis and mortality, without compromising analgesia" British Journal of Cancer, vol. 97, no. 11, pp. 1523-1531, 2007.
43. E. S. Hatzipantelis, Z. D. Pana, N. Gombakis et al., "Endothelial activation and inflammation biomarkers in children and adolescents with sickle cell disease" International Journal of Hematology, vol. 98, no. 2, pp. 158-163, 2013.
44. H. Hyacinth, B. Gee, T. Adamkiewicz et al., "Plasma BDNF and PDGF-AA levels are associated with high TCD velocity and stroke in children with sickle cell anemia" Cytokine, vol. 60, pp. 302-308, 2012.
45. X.Niu, M.Nouraie, A. Campbell et al., "Angiogenic and inflammatory markers of cardiopulmonary changes in children and adolescents with sickle cell disease" PLoS ONE, vol. 4, no. 11, Article ID e7956, 2009.
46. X. Wang, L. C. Loram, K. Ramos et al., "Morphine activates neuro-inflammation in a manner parallel to endotoxin" Proceedings of the National Academy of Sciences of the United States of America, vol. 109, no. 16, pp. 6325-6330, 2012.
47. M. R. Hutchinson, Y. Shavit, P.M. Grace, K. C. Rice, S. F.Maier, and L. R.Watkins, "Exploring the neuroimmunopharmacology of opioids: an integrative review of mechanisms of central immune signaling and their implications for opioid analgesia" Pharmacological Reviews, vol. 63, no. 3, pp. 772-810, 2011.
48. J.D.Belcher, C. Chen, J.Nguyen et al., "Heme triggers TLR4 signaling leading to endothelial cell activation and vaso-occlusion in murine sickle cell disease" Blood, vol. 123, no. 3, pp. 377-390, 2014.
49. S.Ghosh,O.A.Adisa, P.Chappa et al., "Extracellular hemin crisis triggers acute chest syndrome in sickle mice" Journal of Clinical Investigation, vol. 123, no. 11, pp. 4809-4820, 2013.
50. L. A. Michaels, K. Ohene-Frempong, H. Zhao, and S. D. Douglas, "Serum levels of substance P are elevated in patients with sickle cell disease and increase further during vaso-occlusive crisis" Blood, vol. 92, no. 9, pp. 3148-3151, 1998.
51. A. C. Mcclellan, J. C. Luthi, J. R. Lynch et al., "High one year mortality in adults with sickle cell disease and end-stage renal disease" British Journal of Haematology, vol. 159, no. 3, pp. 360-367, 2012.
52. J. I. Scheinman, "Sickle cell disease and the kidney" Nature Clinical Practice Nephrology, vol. 5, no. 2, pp. 78-88, 2009.
53. G. B. Da Silva Junior, A. B. Liborio, and E. De Francesco Daher, "New insights on pathophysiology, clinical manifestations, diagnosis, and treatment of sickle cell nephropathy" Annals of Hematology, vol. 90, no. 12, pp. 1371-1379, 2011.
54. R. Arerangaiah, N. Chalasani, A. Udager et al., "Opioids induce renal abnormalities in tumor-bearing mice" Nephron Experimental Nephrology, vol. 105, no. 3, pp. e80-e89, 2007.
55. M. L.Weber, C. Chen, Y. Li et al., "Morphine stimulates plateletderived growth factor receptor- signalling in mesangial cells in vitro and transgenic sicklemouse kidney in vivo" British Journal of Anaesthesia, vol. 111, no. 6, pp. 1004-1012, 2013.
56. S. Atici, I. Cinel, L. Cinel, N. Doruk, G. Eskandari, and U. Oral, "Liver and kidney toxicity in chronic use of opioids: an experimental long term treatment model" Journal of Biosciences, vol. 30, no. 2, pp. 245-252, 2005.
57. J. F. Borzelleca, J. L. Egle Jr., L. S. Harris, D. N. Johnson, J. B. Terrill, and J. A. Nuite Belleville, "Toxicological evaluation of μ-agonists part I: assessment of toxicity following 30 days of repeated oral dosing of male and female rats with levo-alphaacetylmethadol HCl (LAAM)" Journal of Applied Toxicology, vol. 14, no. 6, pp. 435-446, 1994.
58. P. C. Singhal, M. Pamarthi, R. Shah, D. Chandra, and N. Gibbons, "Morphine stimulates superoxide formation by glomerular mesangial cells" Inflammation, vol. 18, no. 3, pp. 293-299, 1994.
59. B. M. Sharp, W. F. Keane, H. J. Suh, G. Gekker, D. Tsukayama, and P. K. Peterson, "Opioid peptides rapidly stimulate superoxide production by human polymorphonuclear leukocytes and macrophages" Endocrinology, vol. 117, no. 2, pp. 793-795, 1985.
60. M. L. Weber, D. Vang, P. E. Velho et al., "Morphine promotes renal pathology in sickle mice" International Journal ofNephrology and Renovascular Disease, vol. 5, pp. 109-118, 2012.
61. P. C. Singhal, C. Q. Pan, S. Sagar, N. Gibbons, and E. Valderrama, "Morphine enhances deposition of ferritin-antiferritin complexes in the glomerular mesangium" Nephron, vol. 70, no. 2, pp. 229-234, 1995.
62. A. A. Kapasi, N. Gibbons, J. Mattana, and P. C. Singhal, "Morphine stimulates mesangial cell TNF-α and nitrite production" Inflammation, vol. 24, no. 5, pp. 463-476, 2000.
63. M. M. Kilcoyne, D. J. Gocke, J. I. Meltzer et al., "Nephrotic syndrome in heroin addicts" The Lancet, vol. 1, no. 7740, pp. 17-20, 1972.
64. L. Benjamin, "Sickle cell disease" in Advances in Pain Research andTherapy, M. B. Max, R. K. Portenoy, and E. M. Laska, Eds., pp. 317-331, Raven Press,New York,NY, USA, 1991.
65. C. Birken, A. Khambalia, A. Dupuis et al., "Morphine is associated with acute chest syndrome in children hospitalized with sickle cell disease" Hospital Pediatrics, vol. 3, no. 2, pp. 149-155, 2013.
66. S. K. Ballas and C. H. Park, "Severe hypoxemia secondary to acute sternal infarction in sickle cell anemia" Journal of Nuclear Medicine, vol. 32, no. 8, pp. 1617-1618, 1991.
67. P. S. Bellet, K. A. Kalinyak, R. Shukla, M. J. Gelfand, and D. L. Rucknagel, "Incentive spirometry to prevent acute pulmonary complications in sickle cell diseases"The New England Journal of Medicine, vol. 333, no. 11, pp. 699-703, 1995.
68. D. L. Rucknagel, K. A. Kalinyak, and M. J. Gelfand, "Rib infarcts and acute chest syndrome in sickle cell diseases"TheLancet, vol. 337, no. 8745, pp. 831-833, 1991.
69. E. P. Vichinsky, L. D. Neumayr, A. N. Earles et al., "Causes and outcomes of the acute chest syndrome in sickle cell disease" The New England Journal ofMedicine, vol. 342, no. 25, pp. 1855-1865, 2000.
70. L. A. Styles, C. G. Schalkwijk, A. J. Aarsman, E. P. Vichinsky, B. H. Lubin, and F. A. Kuypers, "Phospholipase A2 levels in acute chest syndrome of sickle cell disease" Blood, vol. 87, no. 6, pp. 2573-2578, 1996.
71. M. T. Ashcroft and G. R. Serjeant, "Growth, morbidity, and mortality in a cohort of Jamaican adolescents with homozygous sicke cell disease"West IndianMedical Journal, vol. 30,no. 4, pp. 197-201, 1981.
72. R. H. Sprinkle, T. Cole, S. Smith, and G. R. Buchanan, "Acute chest syndrome in children with sickle cell disease. A retrospective analysis of 100 hospitalized cases" American Journal of Pediatric Hematology/Oncology, vol. 8, no. 2, pp. 105-110, 1986.
73. E. P. Vichinsky and B. H. Lubin, "Sickle cell anemia and related hemoglobinopathies" Pediatric Clinics ofNorthAmerica, vol. 27, no. 2, pp. 429-447, 1980.
74. E. A. Kopecky, S. Jacobson, P. Joshi, and G. Koren, "Systemic exposure tomorphine and the risk of acute chest syndrome in sickle cell disease" Clinical Pharmacology andTherapeutics, vol. 75, no. 3, pp. 140-146, 2004.
75. K. Lewing, K. Britton, M. Debaun, and G. Woods, "The impact of parenteral narcotic choice in the development of acute chest syndrome in sickle cell disease" Journal of Pediatric Hematology/Oncology, vol. 33, no. 4, pp. 255-260, 2011.
76. A. A. Kassim andM. R. DeBaun, "Sickle cell disease, vasculopathy, and therapeutics" Annual Review of Medicine, vol. 64, pp. 451-466, 2013.
77. G. J. Kato,M. T.Gladwin, andM.H. Steinberg, "Deconstructing sickle cell disease: reappraisal of the role of hemolysis in the development of clinical subphenotypes" Blood Reviews, vol. 21, no. 1, pp. 37-47, 2007.
78. F. Parent, D. Bachir, J. Inamo et al., "A hemodynamic study of pulmonary hypertension in sickle cell disease" The New England Journal of Medicine, vol. 365, no. 1, pp. 44-53, 2011.
79. N. Dham, G. Ensing, C.Minniti et al., "Prospective echocardiography assessment of pulmonary hypertension and its potential etiologies in children with sickle cell disease" The American Journal of Cardiology, vol. 104, no. 5, pp. 713-720, 2009.
80. D. Farmakis and A. Aessopos, "Pulmonary hypertension associated with hemoglobinopathies: prevalent but overlooked" Circulation, vol. 123, no. 11, pp. 1227-1232, 2011.
81. M. T. Gladwin and E. Vichinsky, "Pulmonary complications of sickle cell disease" The New England Journal of Medicine, vol. 359, no. 21, pp. 2194-2265, 2008.
82. J. Nguyen, K. Luk, D. Vang et al., "Morphine stimulates cancer progression and mast cell activation and impairs survival in transgenic mice with breast cancer" British Journal of Anaesthesia, vol. 113, pp. i4-i13, 2014.
83. S. Farha, J. Sharp, K. Asosingh et al., "Mast cell number, phenotype, and function in human pulmonary arterial hypertension" Pulmonary Circulation, vol. 2, pp. 220-228, 2012.
84. C.W.-S. Lee, C.-H.Muo, J.-A. Liang, F.-C. Sung, andC.-H. Kao, "Association of intensive morphine treatment and increased stroke incidence in prostate cancer patients: a populationbased nested case-control study" Japanese Journal of Clinical Oncology, vol. 43, no. 8, pp. 776-781, 2013.
85. J. Koch, R. Manworren, L. Clark, C. T. Quinn, G. R. Buchanan, and Z. R. Rogers, "Pilot study of continuous co-infusion of morphine and naloxone in children with sickle cell pain crisis" American Journal of Hematology, vol. 83, no. 9, pp. 728-731, 2008.
86. P.Mucci-LoRusso,B.S.Berman,P.T.Silberstein et al., "Controlledrelease oxycodone compared with controlled-release morphine in the treatment of cancer pain: a randomized, double-blind, parallel-group study" European Journal of Pain, vol. 2, no. 3, pp. 239-249, 1998.
87. P. Klepstad, P. C. Borchgrevink, and S. Kaasa, "Effects on cancer patients health-related quality of life after the start ofmorphine therapy" Journal of Pain and SymptomManagement, vol. 20, no. 1, pp. 19-26, 2000.
88. S. J. Panchal, P.Muller-Schwefe, and J. I.Wurzelmann, "Opioidinduced bowel dysfunction: prevalence, pathophysiology and burden" International Journal of Clinical Practice, vol. 61, no. 7, pp. 1181-1187, 2007.
89. R. K. Portenoy, J. Thomas, M. L. Moehl Boatwright et al., "Subcutaneous methylnaltrexone for the treatment of opioidinduced constipation in patients with advanced illness: a double-blind, randomized, parallel group, dose-ranging study" Journal of Pain and Symptom Management, vol. 35, no. 5, pp. 458-468, 2008.
90. L. T. Pizz, R. Toner, K. Foley et al., "Relationship between potential opioid-related adverse effects and hospital length of stay in patients receiving opioids after orthopedic surgery" Pharmacotherapy, vol. 32, no. 6, pp. 502-514, 2012.
91. J. Y.Wong, B. Carvalho, and E. T. Riley, "Intrathecal morphine 100 and 200 μg for post-cesarean delivery analgesia: a tradeoff between analgesic efficacy and side effects" International Journal of Obstetric Anesthesia, vol. 22, no. 1, pp. 36-41, 2013.
92. X. Nie, Z.-Y. Wen, Z.-Y. Yan, L. Huang, D. Sun, and B. Cheng, "Effects of morphine on rheological properties of rat red blood cells" Clinical Hemorheology and Microcirculation, vol. 22, no. 3, pp. 189-195, 2000.
93. A. Schein,C. Enriquez, T. D. Coates, and J. C.Wood, "Magnetic resonance detection of kidney iron deposition in sickle cell disease: a marker of chronic hemolysis" Journal of Magnetic Resonance Imaging, vol. 28, no. 3, pp. 698-704, 2008.
94. Y. Savov,N. Antonova, E. Zvetkova, Y. Gluhcheva, I. Ivanov, and I. Sainova, "Whole blood viscosity and erythrocyte hematometric indices in chronic heroin addicts" Clinical Hemorheology and Microcirculation, vol. 35, no. 1-2, pp. 129-133, 2006.
95. L. S. Brown Jr., M. J. Hickson, D. C. Ajuluchukwu, and J. Bailey, "Medical disorders in a cohort of New York City drug abusers: Much more than HIV disease" Journal of Addictive Diseases, vol. 12, no. 4, pp. 11-27, 1993.
96. A. R. Zeiger, A. A. Patkar, R. Fitzgerald, A. Lundy, S. K. Ballas, and S. P. Weinstein, "Changes in mu opioid receptors and rheological properties of erythrocytes among opioid abusers" Addiction Biology, vol. 7, no. 2, pp. 207-217, 2002.
97. M. Senturk, O. I. Kufrevioglu, and M. Ciftci, "Effects of some analgesic anaesthetic drugs on human erythrocyte glutathione reductase: an in vitro study" Journal of Enzyme Inhibition and Medicinal Chemistry, vol. 24, no. 2, pp. 420-424, 2009.
98. M. Halabi-Tawil, F. Lionnet, R. Girot, C. Bachmeyer, P. P. Levy, and S. Aractingi, "Sickle cell leg ulcers: a frequently disabling complication and a marker of severity" British Journal of Dermatology, vol. 158, no. 2, pp. 339-344, 2008.
99. P.Connes,Y.Lamarre,M.-D.Hardy-Dessources et al., "Decreased hematocrit-to-viscosity ratio and increased lactate dehydrogenase level in patients with sickle cell anemia and recurrent leg ulcers" PLoS ONE, vol. 8, no. 11,Article ID e79680, 2013.
100. A. J. Madu, A. Ubesie, K. A. Madu, B. Okwor, and C. Anigbo, "Evaluation of clinical and laboratory correlates of sickle leg ulcers"Wound Repair and Regeneration, vol. 21, no. 6, pp. 808-812, 2013.
101. C. P. Minniti, K.-M. H. Delaney, A. M. Gorbach et al., "Vasculopathy, inflammation, and blood flow in leg ulcers of patients with sickle cell anemia" American Journal of Hematology, vol. 89, no. 1, pp. 1-6, 2014.
102. A.M.M.Queiroz, J. Campos, C. Lobo, C. R. Bonini-Domingos, G. Cardoso, and S. K. Ballas, "Leg amputation for an extensive, severe and intractable sickle cell anemia ulcer in a Brazilian patient" Hemoglobin, vol. 38, no. 2, pp. 95-98, 2014.
103. S. K. Ballas, "Treatment of painful sickle cell leg ulcers with topical opioids" Blood, vol. 99, no. 3, p. 1096, 2002.
104. T. Poonawala, B. K. Levay-Young, R. P. Hebbel, and K. Gupta, "Opioids heal ischemic wounds in the rat" Wound Repair and Regeneration, vol. 13, no. 2, pp. 165-174, 2005.
105. M. Gupta, T. Poonawala, M. Farooqui, M. Ericson, and K. Gupta, "Topical fentanyl stimulates healing of ischaemic wounds in diabetic rats" Journal of Diabetes, 2014.
106. P. Farley, "Should topical opioid analgesics be regarded as effective and safe when applied to chronic cutaneous lesions?" Journal of Pharmacy and Pharmacology, vol. 63, no. 6, pp. 747-756, 2011.
107. J. R. Goldsmith, J.M. Uronis, andC. Jobin, "Muopioid signaling protects against acute murine intestinal injury in a manner involving Stat3 signaling" The American Journal of Pathology, vol. 179, no. 2, pp. 673-683, 2011.
108. M. Bigliardi-Qi, C. Gaveriaux-Ruff, K. Pfaltz et al., "Deletion of μ-and κ-opioid receptors in mice changes epidermal hypertrophy, density of peripheral nerve endings, and itch behavior" Journal of Investigative Dermatology, vol. 127, no. 6, pp. 1479-1488, 2007.
109. R. Sim, D. M. Cheong, K. S. Wong, B. M. K. Lee, and Q. Y. Liew, "Prospective randomized, double-blind, placebo-controlled study of pre-and postoperative administration of a COX-2-specific inhibitor as opioid-sparing analgesia in major colorectal surgery" Colorectal Disease, vol. 9, no. 1, pp. 52-60, 2007.
110. J. Moss and C. E. Rosow, "Development of peripheral opioid antagonists: new insights into opioid effects" Mayo Clinic Proceedings, vol. 83, no. 10, pp. 1116-1130, 2008.