Holistic approach to opioid use disorder: Think nitric oxide!

Authors

  • Marvin A. Sackner, MD
  • Jose R. Lopez, MD
  • Veronica Banderas, BA TR
  • Jose A. Adams. MD

DOI:

https://doi.org/10.5055/jom.2019.0543

Keywords:

pain, opioid addiction, nitric oxide, a2 adrenoceptor agonists

Abstract

This review deals with opioid addiction, chronic pain, and an innovative, noninvasive technology with simultaneous, beneficial applications for both conditions. This technology, called passive simulated jogging device (GENTLE JOGGER, JD) targets addiction and pain by increasing endothelial nitric oxide (NO) bioavailability. It can be self-administered while sitting or lying without resorting to multitasking thereby allowing watching television or operating a computer while effortless, physical activity is produced from motorized foot pedals repetitively striking a bumper at 175-190 times per minute which adds small pulses to the circulation. This action increases shear stress (friction) to vascular endothelium that stimulates endothelial nitric oxide synthase (eNOS) to increase NO that decreases oxidative stress and inflammation, and, slows accelerated vascular ageing associated with opioids.

Since the 1970s, clonidine, lofexidine, and dexmedetomidine have been used off-label to suppress opioid withdrawal symptoms precipitated by excessive release of norepinephrine. These pharmacotherapy aids to withdrawal and tapering opioid dosagadrenoceptor agonists that act through eNOS to inhibit norepinephrine. Increasing NO as with JD and/ or in conjunction with opioid agonists should help stabilization, tapering, withdrawal, and relapses stages of addiction. Nitric oxide as increased with JD technology is antinociceptive as demonstrated in chronic and subacute pain states, viz., fibromyalgia, osteoarthritis, peripheral arterial disease, delayed onset of muscle soreness (DOMS), and sickle cell disease. Jogging device decreases elevated blood pressure that is produced with physical inactivity, a risk to opioid use disorder (OUD). Thus, JD provides holistic, cost-effective approach to opioid addiction as well as chronic and subacute pain.

Author Biographies

Marvin A. Sackner, MD

Emeritus Director of Medical Services, Mt Sinai Medical Center of Greater Miami, Miami Beach, Florida

Jose R. Lopez, MD

Research Associate, Mt Sinai Medical Center of Greater Miami, Miami Beach, Florida

Veronica Banderas, BA TR

Research Associate, Sackner Wellness Products LLC, Miami, Florida

Jose A. Adams. MD

Chief, Division of Neonatology, Mt Sinai Medical Center of Greater Miami, Miami Beach, Florida

References

Carise D, Dugosh KL, McLellan AT, et al.: Prescription OxyContin abuse among patients entering addiction treatment. Am J Psychiatry. 2007; 164(11): 1750-1756.

deShazo RD, Johnson M, Eriator I, et al.: Backstories on the US Opioid Epidemic: Good intentions gone bad, an industry gone rogue, and watch dogs gone to sleep. Am J Med. 2018; 131(6): 595-601.

Prekupec MP, Mansky PA, Baumann MH: Misuse of novel synthetic opioids: A deadly new trend. J Addict Med. 2017; 11(4): 256-265.

Schaefer CP, Tome ME, Davis TP. The opioid epidemic: A central role for the blood brain barrier in opioid analgesia and abuse. Fluids Barriers CNS. 2017; 14(1): 32.

Schuckit MA: Treatment of opioid-use disorders. N Engl J Med. 2016; 375(16): 1596-1597.

Zawilska JB: An expanding world of novel psychoactive substances: Opioids. Front Psychiatry. 2017; 8: 110.

Thornton JD, Goyat R, Dwibedi N, et al.: Health-related quality of life in patients receiving long-term opioid therapy: A systematic review with meta-analysis. Qual Life Res. 2017; 26(8): 1955-1967.

Dillie KS, Fleming MF, Mundt MP, et al.: Quality of life associated with daily opioid therapy in a primary care chronic pain sample. J Am Board Fam Med. 2008; 21(2): 108-117.

Krebs E, Kerr T, Wood E, et al.: Characterizing long-term health related quality of life trajectories of individuals with opioid use disorder. J Subst Abuse Treat. 2016; 67: 30-37.

Rajaratnam R, Sivesind D, Todman M, et al.: The aging methadone maintenance patient: Treatment adjustment, long-term success, and quality of life. J Opioid Manag. 2009; 5(1): 27-37.

Sakhuja A, Sztajnkrycer M, Vallabhajosyula S, et al.: National trends and outcomes of cardiac arrest in opioid overdose. Resuscitation. 2017; 121: 84-89.

Chen Q, Larochelle MR, Weaver DT, et al.: Prevention of prescription opioid misuse and projected overdose deaths in the United States. JAMA Netw Open. 2019; 2(2): e187621.

Cicero TJ, Ellis MS: The prescription opioid epidemic: A review of qualitative studies on the progression from initial use to abuse. Dialogues Clin Neurosci. 2017; 19(3): 259-269.

Van Zee A: The promotion and marketing of oxycontin: Commercial triumph, public health tragedy. Am J Public Health. 2009; 99(2): 221-227.

Page MG, Kudrina I, Zomahoun HTV, et al.: Relative frequency and risk factors for long-term opioid therapy following surgery and trauma among adults: A systematic review protocol. Syst Rev. 2018; 7(1): 97.

Younger JW, Chu LF, D'Arcy NT, et al.: Prescription opioid analgesics rapidly change the human brain. Pain. 2011; 152(8): 1803-1810.

Hines LA, Lynskey M, Morley KI, et al.: The relationship between initial route of heroin administration and speed of transition to daily heroin use. Drug Alcohol Rev. 2017; 36(5): 633-638.

Bohnert ASB, Ilgen MA: Understanding links among opioid use, overdose, and suicide. N Engl J Med. 2019; 380(1): 71-79.

Nock NL, Minnes S, Alberts JL: Neurobiology of substance use in adolescents and potential therapeutic effects of exercise for prevention and treatment of substance use disorders. Birth Defects Res. 2017; 109(20): 1711-1729.

McCabe SE, Veliz PT, Boyd CJ, et al.: A prospective study of nonmedical use of prescription opioids during adolescence and subsequent substance use disorder symptoms in early midlife. Drug Alcohol Depend. 2019; 194: 377-385.

McCarty D, Priest KC, Korthuis PT: Treatment and prevention of opioid use disorder: challenges and opportunities. Annu Rev Public Health. 2018; 39: 525-541.

Stein MD, Santiago Rivera OJ, Anderson BJ, et al.: Perceived need for depression treatment among persons entering inpatient opioid detoxification. Am J Addict. 2017; 26(4): 395-399.

Weiss RD, Rao V: The prescription opioid addiction treatment study: What have we learned. Drug Alcohol Depend. 2017; 173(Suppl 1): S48-S54.

McDermott KA, Griffin ML, Connery HS, et al.: Initial response as a predictor of 12-week buprenorphine-naloxone treatment response in a prescription opioid-dependent population. J Clin Psychiatry. 2015; 76(2): 189-194.

Muller AE, Skurtveit S, Clausen T: Many correlates of poor quality of life among substance users entering treatment are not addiction-specific. Health Qual Life Outcomes. 2016; 14: 39.

De Maeyer J, Vanderplasschen W, Lammertyn J, et al.: Current quality of life and its determinants among opiate-dependent individuals five years after starting methadone treatment. Qual Life Res. 2011; 20(1): 139-150.

Jones JD, Vogelman JS, Luba R, et al.: Chronic pain and opioid abuse: Factors associated with health-related quality of life. Am J Addict. 2017; 26(8): 815-821.

Akazawa N, Ra SG, Sugawara J, et al.: Influence of aerobic exercise training on post-exercise responses of aortic pulse pressure and augmentation pressure in postmenopausal women. Front Physiol. 2015; 6: 268.

Booth FW, Roberts CK, Thyfault JP, et al.: Role of inactivity in chronic diseases: Evolutionary insight and pathophysiological mechanisms. Physiol Rev. 2017; 97(4): 1351-1402.

Bouchard C, Blair SN, Katzmarzyk PT: Less sitting, more physical activity, or higher fitness? Mayo Clin Proc. 2015; 90(11): 1533-1540.

Finni T, Haakana P, Pesola AJ, et al.: Exercise for fitness does not decrease the muscular inactivity time during normal daily life. Scand J Med Sci Sports. 2014; 24(1): 211-219.

Watson KB, Carlson SA, Gunn JP, et al.: Physical inactivity among adults aged 50 years and older–United States, 2014. MMWR Morb Mortal Wkly Rep. 2016; 65(36): 954-958.

Cheval B, Tipura E, Burra N, et al.: Avoiding sedentary behaviors requires more cortical resources than avoiding physical activity: An EEG study. Neuropsychologia. 2018; 119: 68-80.

Bardo MT, Compton WM: Does physical activity protect against drug abuse vulnerability? Drug Alcohol Depend. 2015; 153: 3-13.

Ghitza UE, Zhai H, Wu P, et al.: Role of BDNF and GDNF in drug reward and relapse: A review. Neurosci Biobehav Rev. 2010; 35(2): 157-171.

Weiss RD: Adherence to pharmacotherapy in patients with alcohol and opioid dependence. Addiction. 2004; 99(11): 1382-1392.

Litz M, Leslie D: The impact of mental health comorbidities on adherence to buprenorphine: A claims based analysis. Am J Addict. 2017; 26(8): 859-863.

Surbhi S, Graetz I, Wan JY, et al.: The effect of opioid use and mental illness on chronic disease medication adherence in superutilizers. J Manag Care Spec Pharm. 2018; 24(3): 198-207.

Dahlhamer J, Lucas J, Zelaya C, et al:. Prevalence of chronic pain and high-impact chronic pain among adults–United States, 2016. MMWR Morb Mortal Wkly Rep. 2018; 67(36): 1001-1006.

Ambrose KR, Golightly YM: Physical exercise as non-pharmacological treatment of chronic pain: Why and when. Best Pract Res Clin Rheumatol. 2015; 29(1): 120-130.

Manhapra A, Becker WC: Pain and addiction: An integrative therapeutic approach. Med Clin North Am. 2018; 102(4): 745-763.

Bart G: Maintenance medication for opiate addiction: The foundation of recovery. J Addict Dis. 2012; 31(3): 207-225.

Dugosh K, Abraham A, Seymour B, et al.: A systematic review on the use of psychosocial interventions in conjunction with medications for the treatment of opioid addiction. J Addict Med. 2016; 10(2): 93-103.

Pergolizzi JV, Jr, Annabi H, Gharibo C, et al.: The role of lofexidine in management of opioid withdrawal. Pain Ther. 2018; 8(1): 67-78.

Babatunde OO, Jordan JL, Van der Windt DA, et al.: Effective treatment options for musculoskeletal pain in primary care: A systematic overview of current evidence. PLoS One. 2017; 12(6): e0178621.

Da Silva Santos R, Galdino G: Endogenous systems involved in exercise-induced analgesia. J Physiol Pharmacol. 2018; 69(1): 3-13.

Senba E, Kami, K: A new aspect of chronic pain as a lifestyle-related disease. Neurobiol Pain. 2017; 1: 6-15.

Sackner MA, Gummels E, Adams JA: Nitric oxide is released into circulation with whole-body, periodic acceleration. Chest. 2005; 127(1): 30-39.

Sackner MA, Patel S, Adams JA: Changes of blood pressure following initiation of physical inactivity and after external addition of pulses to circulation. Eur J Appl Physiol. 2019; 119(1): 201-211.

Sackner MA: Whole-body, periodic acceleration relieves pain and improves vitality in chronic pain conditions (Abstract). International symposium on nitric oxide, cytokines and inflammation. 2004.

Colledge F, Vogel M, Dursteler-Macfarland K, et al.: A pilot randomized trial of exercise as adjunct therapy in a heroin-assisted treatment setting. J Subst Abuse Treat. 2017; 76: 49-57.

Weinstock J, Wadeson HK, VanHeest JL: Exercise as an adjunct treatment for opiate agonist treatment: Review of the current research and implementation strategies. Subst Abuse. 2012; 33(4): 350-360.

Weinstock J, Farney MR, Elrod NM, et al.: Exercise as an adjunctive treatment for substance use disorders: Rationale and intervention description. J Subst Abuse Treat. 2017; 72: 40-47.

Hutcheson IR, Griffith TM: Release of endothelium-derived relaxing factor is modulated both by frequency and amplitude of pulsatile flow. Am J Physiol. 1991; 261(1 Pt 2): H257-H262.

Adams JA, Moore JE, Jr, Moreno MR, et al.: Effects of periodic body acceleration on the in vivo vasoactive response to Nomega-nitro-L-arginine and the in vitro nitric oxide production. Ann Biomed Eng. 2003; 31(11): 1337-1346.

Abraham WM, Ahmed A, Serebriakov I, et al.: Whole-body periodic acceleration modifies experimental asthma in sheep. Am J Respir Crit Care Med. 2006; 174(7): 743-752.

Adams JA, Bassuk J, Wu D, et al.: Survival and normal neurological outcome after CPR with periodic Gz acceleration and vasopressin. Resuscitation. 2003; 56(2): 215-221.

Adams JA, Bassuk JA, Arias J, et al.: Acute effects of "delayed postconditioning" with periodic acceleration after asphyxia induced shock in pigs. Pediatr Res. 2008; 64(5): 533-537.

Adams JA, Mangino MJ, Bassuk J, et al.: Regional blood flow during periodic acceleration. Crit Care Med. 2001; 29(10): 1983-1988.

Adams JA, Mangino MJ, Bassuk J, et al.: Hemodynamic effects of periodic G(z) acceleration in meconium aspiration in pigs. J Appl Physiol (1985). 2000; 89(6): 2447-2452.

Adams JA, Uryash A, Bassuk J, et al.: Biological basis of neuroprotection and neurotherapeutic effects of whole body periodic acceleration (pGz). Med Hypotheses. 2014; 82(6): 681-687.

Adams JA, Wu H, Bassuk JA, et al. Periodic acceleration (pGz) prior to whole body ischemia reperfusion injury provides early cardioprotective preconditioning. Life Sci. 2010; 86(19-20): 707-715.

Adams JA, Wu H, Bassuk JA, et al.: Periodic acceleration (pGz) acutely increases endothelial and neuronal nitric oxide synthase expression in endomyocardium of normal swine. Peptides. 2009; 30(2): 373-377.

Altamirano F, Perez CF, Liu M, et al.: Whole body periodic acceleration is an effective therapy to ameliorate muscular dystrophy in mdx mice. PLoS One. 2014; 9(9): e106590.

Uryash A, Bassuk J, Kurlansky P, et al.: Antioxidant properties of whole body periodic acceleration (pGz). PLoS One. 2015; 10(7): e0131392.

Uryash A, Bassuk J, Kurlansky P, et al.: Non-invasive technology that improves cardiac function after experimental myocardial infarction: Whole body periodic acceleration (pGz). PLoS One. 2015; 10(3): e0121069.

Martinez A, Arias J, Bassuk JA, et al.: Adrenomedullin is increased by pulsatile shear stress on the vascular endothelium via periodic acceleration (pGz). Peptides. 2008; 29(1): 73-78.

Martinez-Murillo R, Serrano J, Fernandez AP, et al.: Whole-body periodic acceleration reduces brain damage in a focal ischemia model. Neuroscience. 2009; 158(4): 1390-1396.

Rokutanda T, Izumiya Y, Miura M, et al.: Passive exercise using whole-body periodic acceleration enhances blood supply to ischemic hindlimb. Arterioscler Thromb Vasc Biol. 2011; 31(12): 2872-2880.

Lopez JR, Mijares A, Kolster J, et al.: Whole body periodic acceleration improves muscle recovery after eccentric exercise. Med Sci Sports Exerc. 2016; 48(8): 1485-1494.

Sakaguchi M, Fukuda S, Shimada K, et al.: Preliminary observations of passive exercise using whole body periodic acceleration on coronary microcirculation and glucose tolerance in patients with type 2 diabetes. J Cardiol. 2012; 60(4): 283-287.

Adams JA, Pastuszko P, Uryash A, et al.: Whole Body Periodic Acceleration (pGz) as a non-invasive preconditioning strategy for pediatric cardiac surgery. Med Hypotheses. 2018; 110: 144-149.

Fujita M, Sasayama S: Coronary collateral growth and its therapeutic application to coronary artery disease. Circ J. 2010; 74(7): 1283-1289.

Fukuda S, Shimada K, Kawasaki T, et al.: "Passive exercise" using whole body periodic acceleration: effects on coronary microcirculation. Am Heart J. 2010; 159(4): 620-626.

Kohler M, Amann-Vesti BR, Clarenbach CF, et al.: Periodic whole body acceleration: A novel therapy for cardiovascular disease. Vasa. 2007; 36(4): 261-266.

Matsumoto T, Fujita M, Tarutani Y, et al.: Whole-body periodic acceleration enhances brachial endothelial function. Circ J. 2008; 72(1): 139-143.

Miyamoto S, Fujita M, Inoko M, et al.: Effect on treadmill exercise capacity, myocardial ischemia, and left ventricular function as a result of repeated whole body periodic acceleration with heparin pretreatment in patients with angina pectoris and mild left ventricular dysfunction. Am J Cardiol. 2011; 107(2): 168-174.

Sackner MA, Gummels E, Adams JA: Effect of moderate-intensity exercise, whole- body periodic acceleration, and passive cycling on nitric oxide release into circulation. Chest. 2005; 128(4): 2794-2803.

Sackner MA, Gummels EM, Adams JA: Say NO to fibromyalgia and chronic fatigue syndrome: An alternative and complementary therapy to aerobic exercise. Med Hypotheses. 2004; 63(1): 118-123.

Sackner MA: Does fibromyalgia sit in a chair? Symptomatic relief with a simulated jogging device. Fibromyalgia: Open Access. 2017; 2(1): 1-5.

Kitada M, Ogura Y, Koya D: The protective role of Sirt1 in vascular tissue: its relationship to vascular aging and atherosclerosis. Aging (Albany NY). 2016; 8(10): 2290-2307.

Palatini P, Mos L, Mormino P, et al.: Blood pressure changes during running in humans: The "beat" phenomenon. J Appl Physiol (1985). 1989; 67(1): 52-59.

Sackner MA: Is awareness of obesity and type 2 diabetes from physical inactivity in the home and workplace well recognized. Adv Obes Weight Manag Control. 2017; 6(6): 158-162.

Adams JA, Patel S, Lopez JR, et al.: The effects of passive simulated jogging on short-term heart rate variability in a heterogeneous group of human subjects. J Sports Med (Hindawi Publ Corp). 2018; 2018: 4340925.

Caspersen CJ, Powell KE, Christenson GM: Physical activity, exercise, and physical fitness: Definitions and distinctions for health-related research. Public Health Rep. 1985; 100(2): 126-131.

Di Francescomarino S, Sciartilli A, Di Valerio V, et al.: The effect of physical exercise on endothelial function. Sports Med. 2009; 39(10): 797-812.

Ando J, Yamamoto K: Vascular mechanobiology: Endothelial cell responses to fluid shear stress. Circ J. 2009; 73(11): 1983-1992.

Adams JA, Uryash A, Lopez JR, et al.: Whole body periodic acceleration improves survival and microvascular leak in a murine endotoxin model. PLoS One. 2019; 14(1): e0208681.

Giovannitti JA, Jr, Thoms SM, Crawford JJ: Alpha-2 adrenergic receptor agonists:a review of current clinical applications. Anesth Prog. 2015; 62(1): 31-39.

Wang D, Wang Y, Wang Y, et al.: Impact of physical exercise on substance use disorders: A meta-analysis. PLoS One. 2014; 9(10): e110728.

Guthold R, Stevens GA, Riley LM, et al.: Worldwide trends in insufficient physical activity from 2001 to 2016: A pooled analysis of 358 population-based surveys with 1.9 million participants. Lancet Glob Health. 2018; 6(10): e1077-e1086.

Henson J, Dunstan DW, Davies MJ, et al.: Sedentary behavior as a new behavioural target in the prevention and treatment of type 2 diabetes. Diabetes Metab Res Rev. 2016; 32(Suppl 1): 213-220.

Buckley JP, Hedge A, Yates T, et al.: The sedentary office: An expert statement on the growing case for change towards better health and productivity. Br J Sports Med. 2015; 49(21): 1357-1362.

Dempsey PC, Larsen RN, Dunstan DW, et al.: Sitting less and moving more: implications for hypertension. Hypertension. 2018; 72(5): 1037-1046.

Larsen RN, Kingwell BA, Sethi P, et al.: Breaking up prolonged sitting reduces resting blood pressure in overweight/ obese adults. Nutr Metab Cardiovasc Dis. 2014; 24(9): 976-982.

Higgins ST. Editorial: 2nd special issue on behavior change, health, and health disparities. Prev Med. 2015; 80: 1-4.

Wilms B, Ernst B, Thurnheer M, et al.: Correction factors for the calculation of metabolic equivalents (MET) in overweight to extremely obese subjects. Int J Obes (Lond). 2014; 38(11): 1383-1387.

Burns J, Forde C, Dockrell S: Energy expenditure of standing compared to sitting while conducting office tasks. Hum Factors. 2017; 59(7): 1078-1087.

Tyton TN, Scott HM, Horswill CA: Metabolic rate during a cognitive vigilance challenge at alternative workstations. J Occup Environ Med. 2018; 60(6): e307-e311.

Padilla J, Fadel PJ: Prolonged sitting leg vasculopathy: Contributing factors and clinical implications. Am J Physiol Heart Circ Physiol. 2017; 313(4): H722-H728.

Restaino RM, Walsh LK, Morishima T, et al.: Endothelial dysfunction following prolonged sitting is mediated by a reduction in shear stress. Am J Physiol Heart Circ Physiol. 2016; 310(5): H648-H653.

Laina A, Stellos K, Stamatelopoulos K: Vascular ageing: Underlying mechanisms and clinical implications. Exp Gerontol. 2018; 109: 16-30.

Morishima T, Restaino RM, Walsh LK, et al.: Prolonged sitting- induced leg endothelial dysfunction is prevented by fidgeting. Am J Physiol Heart Circ Physiol. 2016; 311(1): H177-H182.

Hsieh HJ, Liu CA, Huang B, et al.: Shear-induced endothelial mechanotransduction: The interplay between reactive oxygen species (ROS) and nitric oxide (NO) and the pathophysiological implications. J Biomed Sci. 2014; 21: 3.

Adams V, Linke A, Krankel N, et al.: Impact of regular physical activity on the NAD(P)H oxidase and angiotensin receptor system in patients with coronary artery disease. Circulation. 2005; 111(5): 555-562.

Bangalore S, Toklu B, Gianos E, et al.: Optimal systolic blood pressure target after SPRINT: Insights from a network meta-analysis of randomized trials. Am J Med. 2017; 130(6): 707-719.

Muntner P, Whelton PK, Woodward M, et al.: A comparison of the 2017 American College of Cardiology/American Heart Association Blood Pressure Guideline and the 2017 American Diabetes Association Diabetes and Hypertension Position Statement for US Adults With Diabetes. Diabetes Care. 2018; 41(11): 2322-2329.

Fiuza-Luces C, Garatachea N, Berger NA, et al.: Exercise is the real polypill. Physiology (Bethesda). 2013; 28(5): 330-358.

Johnson BD, Mather KJ, Wallace JP: Mechanotransduction of shear in the endothelium: Basic studies and clinical implications. Vasc Med. 2011; 16(5): 365-377.

Seals DR, Walker AE, Pierce GL, et al.: Habitual exercise and vascular ageing. J Physiol. 2009; 587(Pt 23): 5541-5549.

Toda N: Age-related changes in endothelial function and blood flow regulation. Pharmacol Ther. 2012; 133(2): 159-176.

Toda N, Nakanishi-Toda M: How mental stress affects endothelial function. Pflugers Arch. 2011; 462(6): 779-794.

Donato AJ, Machin DR, Lesniewski LA: Mechanisms of dysfunction in the aging vasculature and role in age-related disease. Circ Res. 2018; 123(7): 825-848.

Zheng C, Liu Z: Vascular function, insulin action, and exercise: An intricateinterplay. Trends Endocrinol Metab. 2015; 26(6): 297-304.

Lobelo F, Rohm Young D, Sallis R, et al.: Routine assessment and promotion of physical activity in healthcare settings: A scientific statement from the American Heart Association. Circulation. 2018; 137(18): e495-e522.

Duvivier B, Bolijn JE, Koster A, et al.: Reducing sitting time versus adding exercise: Differential effects on biomarkers of endothelial dysfunction and metabolic risk. Sci Rep. 2018; 8(1): 8657.

Walker AE, Kaplon RE, Pierce GL, et al.: Prevention of age-related endothelial dysfunction by habitual aerobic exercise in healthy humans: Possible role of nuclear factor kappaB. Clin Sci (Lond). 2014; 127(11): 645-654.

Doukas N: Older adults prescribed methadone: A review of the literature across the life span from opiate initiation to methadone maintenance treatment. Curr Drug Abuse Rev. 2014; 7(3): 165-173.

Reece AS, Hulse GK: Impact of opioid pharmacotherapy on arterial stiffness and vascular ageing: Cross-sectional and longitudinal studies. Cardiovasc Toxicol. 2013; 13(3): 254-266.

Reece AS, Hulse GK: Impact of lifetime opioid exposure on arterial stiffness and vascular age: Cross-sectional and longitudinal studies in men and women. BMJ Open. 2014; 4(6): e004521.

Reece AS, Hulse GK: Duration of opiate exposure as a determinant of arterial stiffness and vascular age in male opiate dependence: A longitudinal study. J Clin Pharm Ther. 2014; 39(2): 158-167.

Gfroerer J, Penne M, Pemberton M, et al.: Substance abuse treatment need among older adults in 2020: The impact of the aging baby-boom cohort. Drug Alcohol Depend. 2003; 69(2): 127-135.

Maillard P, Mitchell GF, Himali JJ, et al.: Effects of arterial stiffness on brain integrity in young adults from the Framingham heart study. Stroke. 2016; 47(4): 1030-1036.

van Sloten TT, Mitchell GF, Sigurdsson S, et al.: Associations between arterial stiffness, depressive symptoms and cerebral small vessel disease: Cross-sectional findings from the AGES-Reykjavik Study. J Psychiatry Neurosci. 2016; 41(3): 162-168.

van Sloten TT, Protogerou AD, Henry RM, et al.: Association between arterial stiffness, cerebral small vessel disease and cognitive impairment: A systematic review and meta-analysis. Neurosci Biobehav Rev. 2015; 53: 121-130.

Fukuda D, Yoshiyama M, Shimada K, et al.: Relation between aortic stiffness and coronary flow reserve in patients with coronary artery disease. Heart. 2006; 92(6): 759-762.

Gould KL, Johnson NP: Coronary physiology beyond coronary flow reserve in microvascular angina: JACC state-of-the-art review. J Am Coll Cardiol. 2018; 72(21): 2642-2662.

Tritakis V, Tzortzis S, Ikonomidis I, et al.: Association of arterial stiffness with coronary flow reserve in revascularized coronary artery disease patients. World J Cardiol. 2016; 8(2): 231-239.

Esmaeili Nadimi A, Pour Amiri F, Sheikh Fathollahi M, et al.: Opium addiction as an independent risk factor for coronary microvascular dysfunction: A case-control study of 250 consecutive patients with slow-flow angina. Int J Cardiol. 2016; 219: 301-307.

Marinescu MA, Loffler AI, Ouellette M, et al.: Coronary microvascular dysfunction, microvascular angina, and treatment strategies. JACC Cardiovasc Imaging. 2015; 8(2): 210-220.

Ahmadi-Abhari S, Sabia S, Shipley MJ, et al.: Physical activity, sedentary behavior, and long-term changes in aortic stiffness: The Whitehall II study. J Am Heart Assoc. 2017; 6(8).

Ashor AW, Lara J, Siervo M, et al.: Effects of exercise modalities on arterial stiffness and wave reflection: A systematic review and meta- analysis of randomized controlled trials. PLoS One. 2014; 9(10): e110034.

Kohn JC, Lampi MC, Reinhart-King CA: Age-related vascular stiffening: Causes and consequences. Front Genet. 2015; 6: 112.

Isabelle M, Simonet S, Ragonnet C, et al.: Chronic reduction of nitric oxide level in adult spontaneously hypertensive rats induces aortic stiffness similar to old spontaneously hypertensive rats. J Vasc Res. 2012; 49(4): 309-318.

Costantino S, Paneni F, Cosentino F: Ageing, metabolism and cardiovasculardisease. J Physiol. 2016; 594(8): 2061-2073.

Hayashi T, Matsui-Hirai H, Miyazaki-Akita A, et al.: Endothelial cellular senescence is inhibited by nitric oxide: implications in atherosclerosis associated with menopause and diabetes. Proc Natl Acad Sci USA. 2006; 103(45): 17018-17023.

Foreman DL, Sanders M, Bloor CM: Total and regional cerebral blood flow during moderate and severe exercise in miniature swine. J Appl Physiol. 1976; 40(2): 191-195.

Stebbins CL, Symons JD: Role of angiotensin II in hemodynamic responses to dynamic exercise in miniswine. J Appl Physiol (1985). 1995; 78(1): 185-190.

Denier N, Gerber H, Vogel M, et al.: Reduction in cerebral perfusion after heroin administration: A resting state arterial spin labeling study. PLoS One. 2013; 8(9): e71461.

Jellinger KA: Pathogenesis and treatment of vascular cognitive impairment. Neurodegener Dis Manag. 2014; 4(6): 471-490.

Kurita GP, de Mattos Pimenta CA, Braga PE, et al.: Cognitive function in patients with chronic pain treated with opioids: Characteristics and associated factors. Acta Anaesthesiol Scand. 2012; 56(10): 1257-1266.

Puca AA, Carrizzo A, Ferrario A, et al.: Endothelial nitric oxide synthase, vascular integrity and human exceptional longevity. Immun Ageing. 2012; 9(1): 26.

Cheng GL, Zeng H, Leung MK, et al.: Heroin abuse accelerates biological aging: A novel insight from telomerase and brain imaging interaction. Transl Psychiatry. 2013; 3: e260.

Cunha-Oliiveira TC, Rego AC, et al.: Oxidative stress and drugs of abuse: An update. Mini-Rev Org Chem. 2013; 10: 1-14.

Lam CF, Liu YC, Tseng FL, et al.: High-dose morphine impairs vascular endothelial function by increased production of superoxide anions. Anesthesiology. 2007; 106(3): 532-537.

Takase B, Hattori H, Tanaka Y, et al. Acute effect of whole-body periodic acceleration on brachial flow-mediated vasodilatation assessed by a novel semi-automatic vessel chasing UNEXEF18G system. J Cardiovasc Ultrasound. 2013; 21(3): 130-136.

Salvemini D: Peroxynitrite and opiate antinociceptive tolerance: A painful reality. Arch Biochem Biophys. 2009; 484(2): 238-244.

Muscoli C, Cuzzocrea S, Ndengele MM, et al.: Therapeutic manipulation of peroxynitrite attenuates the development of opiate-induced antinociceptive tolerance in mice. J Clin Invest. 2007; 117(11): 3530-3539.

Matsuda M, Huh Y, Ji RR: Roles of inflammation, neurogenic inflammation, and neuroinflammation in pain. J Anesth. 2019; 33(1): 131-139.

Shen CH, Tsai RY, Wong CS: Role of neuroinflammation in morphine tolerance: Effect of tumor necrosis factor-alpha. Acta Anaesthesiol Taiwan. 2012; 50(4): 178-182.

Allen SJ, Dawbarn D: Clinical relevance of the neurotrophins and their receptors. Clin Sci (Lond). 2006; 110(2): 175-191.

Peregud DI, Yakovlev AA, Stepanichev MY, et al.: Expression of BDNF and TrkB phosphorylation in the rat frontal cortex during morphine withdrawal are NO dependent. Cell Mol Neurobiol. 2016; 36(6): 839-849.

Carnicella S, Ron D: GDNF–A potential target to treat addiction. Pharmacol Ther. 2009; 122(1): 9-18.

Marie C, Pedard M, Quirie A, et al.: Brain-derived neurotrophic factor secreted by the cerebral endothelium: A new actor of brain function? J Cereb Blood Flow Metab. 2018; 38(6): 935-949.

Monnier A, Prigent-Tessier A, Quirie A, et al.: Brain-derived neurotrophic factor of the cerebral microvasculature: A forgotten and nitric oxide-dependent contributor of brain-derived neurotrophic factor in the brain. Acta Physiol (Oxf). 2017; 219(4): 790-802.

Lopez JR, Uryash A, Kolster J, et al.: Enhancing endogenous nitric oxide by whole body periodic acceleration elicits neuroprotective effects in dystrophic neurons. Mol Neurobiol. 2018; 55(11): 8680-8694.

Pang PT, Teng HK, Zaitsev E, et al.: Cleavage of proBDNF by tPA/plasmin is essential for long-term hippocampal plasticity. Science. 2004; 306(5695): 487-491.

Maglione MA, Raaen L, Chen C, et al.: Effects of medication assisted treatment (MAT) for opioid use disorder on functional outcomes: A systematic review. J Subst Abuse Treat. 2018; 89: 28-51.

Sofuoglu M, DeVito E, Carroll K: Pharmacological and behavioral treatment of opioid use disorder. PRCP Adv. 2018: 12.

Toce MS, Chai PR, Burns MM, et al.: Pharmacologic treatment of opioid use disorder: A review of pharmacotherapy, adjuncts, and toxicity. J Med Toxicol. 2018; 14(4): 306-322.

Shipton EA, Shipton EE, Shipton AJ: A review of the opioid epidemic: What do we do about it? Pain Ther. 2018; 7(1): 23-36.

Feldman J, Fellmann L, Bousquet P: The central hypotensive effect induced by alpha 2-adrenergic receptor stimulation is dependent on endothelial nitric oxide synthase. J Hypertens. 2008; 26(5): 1033-1036.

Fresquez-Chavez KR, Fogger S: Reduction of opiate withdrawal symptoms with use of clonidine in a county jail. J Correct Health Care. 2015; 21(1): 27-34.

Gold MS, Redmond DE, Jr., Kleber HD. Clonidine blocks acute opiate-withdrawal symptoms. Lancet. 1978; 2(8090): 599-602.

Gold MS, Redmond DE, Jr., Kleber HD: Noradrenergic hyperactivity in opiate withdrawal supported by clonidine reversal of opiate withdrawal. Am JPsychiatry. 1979; 136(1): 100-102.

Nunes EV, Gordon M, Friedmann PD, et al.: Relapse to opioid use disorder after inpatient treatment: Protective effect of injection naltrexone. J Subst Abuse Treat. 2018; 85: 49-55.

Salarian A, Kadkhodaee M, Zahmatkesh M, et al.: Opioid use disorder induces oxidative stress and inflammation: The attenuating effect of methadone maintenance treatment. Iran J Psychiatry. 2018; 13(1): 46-54.

Cury Y, Picolo G, Gutierrez VP, et al.: Pain and analgesia: The dual effect of nitric oxide in the nociceptive system. Nitric Oxide. 2011; 25(3): 243-254.

Strauch B, Herman C, Dabb R, et al.: Evidence-based use of pulsed electromagnetic field therapy in clinical plastic surgery. Aesthet Surg J. 2009; 29(2): 135-143.

Tick H, Nielsen A, Pelletier KR, et al.: Evidence-based nonpharmacologic strategies for comprehensive pain care: The consortium pain task force white paper. Explore (NY). 2018; 14(3): 177-211.

Doughty B, Morgenson D, Brooks T: Lofexidine: A newly FDA-approved, nonopioid treatment for opioid withdrawal. Ann Pharmacother. 2019: 53(7): 746-753.

Charney DS, Redmond DE, Jr, Galloway MP, et al.: Naltrexone precipitated opiate withdrawal in methadone addicted human subjects: evidence for noradrenergic hyperactivity. Life Sci. 1984; 35(12): 1263-1272.

Gertler R, Brown HC, Mitchell DH, et al.: Dex medetomidine: A novelsedative-analgesic agent. Proc (Bayl Univ Med Cent). 2001; 14(1): 13-21.

Li HJ, Li CJ, Wei XN, et al.: Dexmedetomidine in combination with morphine improves postoperative analgesia and sleep quality in elderly patients after open abdominal surgery: A pilot randomized control trial. PLoS One. 2018; 13(8): e0202008.

Peng K, Zhang J, Meng XW, et al.: Optimization of postoperative intravenous patient-controlled analgesia with opioid-dexmedetomidine combinations: An updated meta-analysis with trial sequential analysis of randomized controlled trials. Pain Physician. 2017; 20(7): 569-596.

de Moura RS, Rios AA, Santos EJ, et al.: Role of the NO-cGMP pathway in the systemic antinociceptive effect of clonidine in rats and mice. Pharmacol Biochem Behav. 2004; 78(2): 247-253.

Dobrucki LW, Cabrera CL, Bohr DF, et al.: Central hypotensive action of clonidine requires nitric oxide. Circulation. 2001; 104(16): 1884-1886.

Sy GY, Bruban V, Bousquet P, et al.: Nitric oxide and central antihypertensive drugs: one more difference between catecholamines and imidazolines. Hypertension. 2001; 37(2): 246-249.

Hser YI, Mooney LJ, Saxon AJ, et al.: Chronic pain among patients with opioid use disorder: Results from electronic health records data. J Subst Abuse Treat. 2017; 77: 26-30.

Hung AL, Lim M, Doshi TL: Targeting cytokines for treatment of neuropathic pain. Scand J Pain. 2017; 17: 287-293.

Anastas T, Colpitts K, Ziadni M, et al.: Characterizing chronic pain in late adolescence and early adulthood: Prescription opioids, marijuana use, obesity, and predictors for greater pain interference. Pain Rep. 2018; 3(6): e700.

Carter S, Hartman Y, Holder S, et al.: Sedentary behavior and cardiovascular disease risk: Mediating mechanisms. Exerc Sport Sci Rev. 2017; 45(2): 80-86.

Gratas-Delamarche A, Derbre F, Vincent S, et al.: Physical inactivity, insulin resistance, and the oxidative-inflammatory loop. Free Radic Res. 2014; 48(1): 93-108.

Thosar SS, Bielko SL, Mather KJ, et al.: Effect of prolonged sitting and breaks in sitting time on endothelial function. Med Sci Sports Exerc. 2015; 47(4): 843-849.

Salvemini D, Little JW, Doyle T, et al.: Roles of reactive oxygen and nitrogen species in pain. Free Radic Biol Med. 2011; 51(5): 951-966.

Volkow ND, McLellan AT: Opioid abuse in chronic pain–misconceptions and mitigation strategies. N Engl J Med. 2016; 374(13): 1253-1263.

Dunn KE, Brooner RK, Clark MR: Severity and interference of chronic pain in methadone-maintained outpatients. Pain Med. 2014; 15(9): 1540-1548.

Serravite DH, Perry A, Jacobs KA, et al.: Effect of whole-body periodic acceleration on exercise-induced muscle damage after eccentric exercise. Int J Sports Physiol Perform. 2014; 9(6): 985-992.

Valentin GH, Pilegaard MS, Vaegter HB, et al.: Prognostic factors for disability and sick leave in patients with subacute non-malignant pain: A systematic review of cohort studies. BMJ Open. 2016; 6(1): e007616.

Al-Boloushi Z, Lopez-Royo MP, Arian M, et al.: Minimally invasive non-surgical management of plantar fasciitis: A systematic review. J Bodyw Mov Ther. 2019; 23(1): 122-137.

Dunlop DD, Song J, Arnston EK, et al.: Sedentary time in US older adults associated with disability in activities of daily living independent of physical activity. J Phys Act Health. 2015; 12(1): 93-101.

Dempsey PC, Sacre JW, Larsen RN, et al.: Interrupting prolonged sitting with brief bouts of light walking or simple resistance activities reduces resting blood pressure and plasma noradrenaline in type 2 diabetes. J Hypertens. 2016; 34(12): 2376-2382.

Rasouli J, Lekhraj R, White NM, et al.: Attenuation of interleukin- 1beta by pulsed electromagnetic fields after traumatic brain injury. Neurosci Lett. 2012; 519(1): 4-8.

Uryash A, Wu H, Bassuk J, et al.: Preconditioning with periodic acceleration (pGz) provides second window of cardioprotection. Life Sci. 2012; 91(5-6): 178-185.

Aronov S, Ben-Abraham R, Givati-Divshi D, et al.: Cerebroventricular injection of clonidine causes analgesia mediated by a nitrogen pathway. Drug Metabol Drug Interact. 2005; 21(1): 55-66.

Kosten TR, Baxter LE: Review article: Effective management of opioid withdrawal symptoms: A gateway to opioid dependence treatment. Am J Addict. 2019; 28(2): 55-62.

Teut M, Knilli J, Daus D, et al.: Qigong or yoga versus no intervention in older adults with chronic low back pain-a randomized controlled trial. J Pain. 2016; 17(7): 796-805.

Teut M, Ullmann A, Ortiz M, et al.: Pulsatile dry cupping in chronic low back pain–A randomized three-armed controlled clinical trial. BMC Complement Altern Med. 2018; 18(1): 115.

Ma SX: Nitric oxide signaling molecules in acupoints: Toward mechanisms of acupuncture. Chin J Integr Med. 2017; 23(11): 812-815.

Barbaresko J, Rienks J, Nothlings U: Lifestyle indices and cardiovascular disease risk: A meta-analysis. Am J Prev Med. 2018; 55(4): 555-564.

Fang J, Moore L, Loustalot F, et al.: Reporting of adherence to healthy lifestyle behaviors among hypertensive adults in the 50 states and the District of Columbia, 2013. J Am Soc Hypertens. 2016; 10(3): 252-262.

Chen D, Shen J, Zhao W, et al.: Osteoarthritis: Toward a comprehensive understanding of pathological mechanism. Bone Res. 2017; 5: 16044.

Krebs EE, Gravely A, Nugent S, et al.: Effect of opioid vs nonopioid medications on pain-related function in patients with chronic back pain or hip or knee osteoarthritis pain: The SPACE randomized clinical trial. JAMA. 2018; 319(9): 872-882.

Lee YC, Shmerling RH: The benefit of nonpharmacologic therapy to treat symptomatic osteoarthritis. Curr Rheumatol Rep. 2008; 10(1): 5-10.

Goh SL, Persson MSM, Stocks J, et al.: Relative efficacy of different exercises for pain, function, performance and quality of life in knee and hip osteoarthritis: Systematic review and network meta-analysis. Sports Med. 2019; 49(5): 743-761.

Abramson SB: Nitric oxide in inflammation and pain associated with osteoarthritis. Arthritis Res Ther. 2008; 10(Suppl 2): S2.

Segura-Jimenez V, Borges-Cosic M, Soriano-Maldonado A, et al.: Association of sedentary time and physical activity with pain, fatigue, and impact of fibromyalgia: The al-Andalus study. Scand J Med Sci Sports. 2017; 27(1): 83-92.

Peng X, Robinson RL, Mease P, et al.: Long-term evaluation of opioid treatment in fibromyalgia. Clin J Pain. 2015; 31(1): 7-13.

Argoff CE, Emir B, Whalen E, et al.: Pregabalin improves pain scores in patients with fibromyalgia irrespective of comorbid osteoarthritis. Pain Med. 2016; 17(11): 2100-2108.

Boers M, Buttgereit F, Saag K, et al.: What is the relationship between morning symptoms and measures of disease activity in patients with rheumatoid arthritis? Arthritis Care Res (Hoboken). 2015; 67(9): 1202-1209.

Cleeland CS, Ryan KM: Pain assessment: Global use of the brief pain inventory. Ann Acad Med Singapore. 1994; 23(2): 129-138.

Martins JC. Patients' satisfaction with information on disease and morbidity. Rev Lat Am Enfermagem. 2009; 17(3): 335-340.

Mendoza TR, Wang XS, Cleeland CS, et al.: The rapid assessment of fatigue severity in cancer patients: Use of the Brief Fatigue Inventory. Cancer. 1999; 85(5): 1186-1196.

Zung WW: A self-rating depression scale. Arch Gen Psychiatry. 1965; 12: 63-70.

Zung WW: A rating instrument for anxiety disorders. Psychosomatics. 1971; 12(6): 371-379.

Fanari Z, Weintraub WS: Cost-effectiveness of medical, endovascular and surgical management of peripheral vascular disease. Cardiovasc Revasc Med. 2015; 16(7): 421-425.

Hamburg NM, Creager MA: Pathophysiology of intermittent claudication in peripheral artery disease. Circ J. 2017; 81(3): 281-289.

Money SR, Herd JA, Isaacsohn JL, et al.: Effect of cilostazol on walking distances in patients with intermittent claudication caused by peripheral vascular disease. J Vasc Surg. 1998; 27(2): 267-274; discussion 274-265.

Ismaeel A, Brumberg RS, Kirk JS, et al.: Oxidative stress and arterial dysfunction in peripheral artery disease. Antioxidants (Basel). 2018; 7(10).

McDermott MM: Functional impairment in peripheral artery disease and how to improve it in 2013. Curr Cardiol Rep. 2013; 15(4): 347.

Agarwal S, Sud K, Shishehbor MH: Nationwide trends of hospital admission and outcomes among critical limb ischemia patients: From 2003-2011. J Am Coll Cardiol. 2016; 67(16): 1901-1913.

Teraa M, Conte MS, Moll FL, et al.: Critical limb ischemia: Current trends and future directions. J Am Heart Assoc. 2016; 5(2).

Alvarez OM, Wendelken ME, Markowitz L, et al.: Effect of high-pressure, intermittent pneumatic compression for the treatment of peripheral arterial disease and critical limb ischemia in patients without a surgical option. Wounds. 2015; 27(11): 293-301.

Buschmann EE, Brix M, Li L, et al.: Adaptation of external counterpulsation based on individual shear rate therapy improves endothelial function and claudication distance in peripheral artery disease. Vasa. 2016; 45(4): 317-324.

Dakour-Aridi H, Arora M, Nejim B, et al.: Association between drug use and in-hospital outcomes after infrainguinal bypass for peripheral arterial occlusive disease. Ann Vasc Surg. 2019; 58: 122-133.

Silva JR, Rumpf MC, Hertzog M, et al.: Acute and residual soccer match-related fatigue: A systematic review and meta-analysis. Sports Med. 2018; 48(3): 539-583.

Ranchordas MK, Rogerson D, Soltani H, et al.: Antioxidants for preventing and reducing muscle soreness after exercise: A cochrane systematic review. Br J Sports Med. 2018.

Viinikka L: Nitric oxide as a challenge for the clinical chemistry laboratory. Scand J Clin Lab Invest. 1996; 56(7): 577-581.

Vanhoutte PM, Zhao Y, Xu A, et al.: Thirty years of saying NO: Sources, fate, actions, and misfortunes of the endothelium-derived vasodilator mediator. Circ Res. 2016; 119(2): 375-396.

Buys ES, Zimmer DP, Chickering J, et al.: Discovery and development of next generation sGC stimulators with diverse multidimensional pharmacology andbroad therapeutic potential. Nitric Oxide. 2018; 78: 72-80.

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Published

11/01/2019

How to Cite

Sackner, MD, M. A., J. R. Lopez, MD, V. Banderas, BA TR, and J. A. Adams. MD. “Holistic Approach to Opioid Use Disorder: Think Nitric Oxide!”. Journal of Opioid Management, vol. 15, no. 6, Nov. 2019, pp. 521-55, doi:10.5055/jom.2019.0543.

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Review Articles