Holistic approach to opioid use disorder: Think nitric oxide!

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.

Portable Gentle Jogger Improves Glycemic Indices in Type 2 Diabetic and Healthy Subjects Living at Home: A Pilot Study

“…The Gentle Jogger does not require multitasking and can be self-administered while watching television, reading, operating a computer and dining, etc. In another study of 26 seated volunteers, mean age 44 years SD 15, BMI 28 SD 5, Gentle Jogger increased METS 15% with no individual exceeding 1.5 METS [26].…”

L-cysteine ethyl ester prevents and reverses acquired physical dependence on morphine in male Sprague Dawley rats

“…Frontiers in Pharmacology frontiersin.org Noda and Nabeshima, 2004;Glass, 2011;Fluyau et al, 2020), muscarinic receptors (Marshall and Buccafusco, 1987;Holland et al, 1993), corticotropin-releasing factor (CRF) receptor (CRF1) (García-Carmona et al, 2015), tachykinin receptors (Michaud and Couture, 2003), voltage-gated Ca 2+ -channels (Tokuyama et al, 1995;Dogrul et al, 2002;Esmaeili-Mahani et al, 2008;Alboghobeish et al, 2019), adenylyl cyclase superactivation and opioid receptor phosphorylation (Avido-Reiss et al, 1996;Avido-Reiss et al, 1997;Wang et al, 1999;Eckhardt et al, 2000), oxidative stress (Xu et al, 2006;Mori et al, 2007;Abdel-Zaher et al, 2013;Mansouri et al, 2020;Ward et al, 2020;Houshmand et al, 2021), and the nitric oxide-cGMP signaling cascade (Adams et al, 1993;Cappendijk et al, 1993;Majeed et al, 1994;Vaupel et al, 1995a;Buccafusco et al, 1995;Vaupel et al, 1995b;Herman et al, 1995;Leza et al, 1995;London et al, 1995;Dambisya and Lee, 1996;Bhatt and Kumar, 2015;Tsakova et al, 2015;Sackner et al, 2019;Gledhill and Babey, 2021). Since L-CYSee blunted the expression of all NLXprecipitated behavioral (except for sneezing), physical (body weight loss and hypothermia), and cardiorespiratory (hypertension, tachycardia, and incidence of apneas) phenomena, it is tempting to assume that L-CYSee interrupts fun...…”

The N‐methyl‐D‐aspartate receptor antagonist ketamin exerts analgesic effects via modulation of the nitric oxide pathway

“…Various studies have shown that NOS activation plays an important role in central and peripheral modulation of pain by subsequent NO production [7][8][9][10]. A body of evidence suggests that NO and cyclic guanosine monophosphate (cGMP) primarily aid in the processing of pain signals in the spinal cord; however, contradictory effects on analgesia have been observed depending on various factors such as the stage of NO involvement, concentration, site of action, and the identity of the pain stimuli [11][12][13].…”