Zhang L, Boysen PG. New Persistent Opioid Abuse and the Brain Reward Circuit. J Anesthesiol & Pain Therapy. 2020;1(1):11-13 Letter to the Editor Open Access New Persistent Opioid Abuse and the Brain Reward Circuit Ly Zhang*, Philip G. Boysen Department of Anesthesiology, University of Mississippi Medical Center, The Mississippi Critical Care Organization, USA Article Info New persistent opioid abuse in peri-operative and peri- procedural patients is reported to be ~6% in two large population- Article Notes 1 Received: December 06, 2019 based studies . In addressing the opioid crisis the CDC has developed Accepted: April 08, 2020 2 *Correspondence: approved opioids are prescribed by licensed professionals . The *Dr. Ly Zhang, Department of Anesthesiology, University of three categories. The first is prescription drugs, when legal and Mississippi Medical Center, The Mississippi Critical Care and fentanyl . Over time CDC data indicates a sharp uptick in opioid Organization, USA; Email: [email protected]. second and third3,4 categories involve illicit drugs, specifically heroin ©2020 Zhang L. This article is distributed under the terms of the prescription drugs5. Understanding the neurobiology of addiction Creative Commons Attribution 4.0 International License. deaths for heroin and fentanyl, but a flat incidence of overdose with and public health issues are integral to the understanding of how adds insight to the problem and treatment. In addition, the social the brain reward circuit is activated in the first place. human primates 50 years ago. Rats taught to push a lever to self – The brain reward circuit was described in rodents, then in non- aspectsadminister of addictive addictive behavior. drugs (heroin, When the cocaine environment amphetamines) is subsequently would not eat or sleep, began excessive lever-pushing, and exhibited other months and can be activated in response to addiction cues or stress6. withdrawn, the pleasure is not forgotten, but remains intact for key to this physiology is in the brain mesolimbic system located in In effect, the reward circuit is commandeered by the 7drug.. The VTAThe the ventral tegmental area (VTA) in the base of the brain targets the nucleus accumbens (NA) by sending dopamine 8.from its terminal to the NA. When the dopamine pathway is ablated, experimentalNeurotransmitters animals showactivate no interest the amygdala in substances to assess of abuse whether the experience is pleasurable or aversive, and whether it should9. The be repeated or avoided, thus forging the connection10. The between frontal the experience itself and other cues to that experience11. hippocampus records the memory of the experience cortex processes information to determine ultimate behavior to triggersOver the and past cues. 15 years, Diverse MRI drugs and PETcan activatescans have the confirmedbrain reward the existence of the brain reward circuit in humans, including responses and repackaging of the DA back into the VTA follows. Cocaine disables circuitry to release DA from the axon into synaptic clefts; reuptake VTAthe transporter and have a directprotein effect that onreturns cellular the function DA to the12. VTA, resulting in a “DA flood” at the terminals. Opioids bind directly to neurons in the characteristicAddiction progressesof withdrawal from if tolerancethe drug isto cutescalation off or discontinued. of drug use, then dependence, and finally the painful and emotional reactions Page 11 of 13 Zhang L, Boysen PG. New Persistent Opioid Abuse and the Brain Reward Circuit. J Anesthesiol & Pain Therapy. 2020;1(1):11-13 Journal of Anesthesiology and Pain Therapy Wit t hin the NA are cell transcription factors, and other herapy to treat addiction. Finally, it establishes the need to neurotransmitters, responsible for the final common examine clinical practices. 17 pathway to addiction. Cyclic AMP Response Element . He describes addiction as a In September 2001, Goldstein published Addiction: Binding protein (CREB) regulates gene expression to From Biology to Public Policy suppressingactively produce the reward dynorphin, circuit awhich natural results molecule in tolerance. with opioid like effects Dynorphin inhibits neurons in the VTA, brain disease, and also provides factual information about addiction as “a much neglected societal problem”. This of days13. The elaboration of CREB and its effects lasts only a matter position is corroborated by the aforementioned CDC report, resultedpreviously in noalluded death increasesto, Opioid due Overdose: to commonly Understanding prescribed rises to a peak level which will last for months. The the Epidemic, indicating that regulation and public policy riseAnother in this transcriptiontranscription factor,factor deltais accompaniedFosB gradually by heroin and synthetic fentanyl caused a marked increase in microscopic anatomic changes. Dendrites elaborate spiny opioids starting from 2010,5 whereas the illicit18 use of projections resulting in a bushy appearance that parallels the intransigence of addiction. Glutamate is the major ■ overdose deaths. (Figure) , Published data include : drug overdose. ■ From 1999 to 2017, more than 700,000 people died from neurotransmitter for14 the amygdala, hippocampus, frontal involving an opioid. cortex,There and are the some VTA individuals with a genetic predisposition In 2017, there were 70,200 overdose deaths, 68% to addiction ■ 15,16 (including prescription opioids and illegal opioids like . For a perioperative patient, it can take In 2017, the number of deaths involving opioids circuitry.only a few This instances can occur of exposure with prescriptive to a drug or (or recreational even only higher than 1999. one) for an addictive drug to “hi-jack” the brain reward heroin and illicitly manufactured fentanyl) was 6 times rewarddrugs, includingcircuitry corroboratesalcohol and addiction nicotine, as and a disease overeating with and compulsive gambling. Thus, understanding the brain The WONDER study (wide-ranging online data for craving and recidivism that is part of addictive behavior. epidemiologic research), part of the CDC and published definitive alterations in neurobiology. It also explains theic everyby the day National from an Center opioid for overdose Health 19Statistics,. reported that in the same year, 2017, an average of 130 Americans died It points the way to future research to provide specif Figure: https://www.cdc.gov/drugoverdose/epidemic/index.html Page 12 of 13 Zhang L, Boysen PG. New Persistent Opioid Abuse and the Brain Reward Circuit. J Anesthesiol & Pain Therapy. 2020;1(1):11-13 Journal of Anesthesiology and Pain Therapy common pathway or the reinforcing effects of drug abuse? Neurosci WAVE 1: During the 1990 – 2010 time frame a rise The CDC report identified three waves of opioid deaths: 8. Biobehav Rev. 2006; 30: 215-238. opioids and methadone was noted20. 6370.Trezza V, Damstegt R, Achterberg EJ, et al. Nucleus accumbens mu in prescribed opioids, both natural and semi-synthetic opioid receptors mediate social reward. J Neurosci. 2011; 17: 6362- WAVE 2: 9. increase in overdose deaths involving heroin. Starting in Jackson ME, Moghaddam B. Amygdala regulation of nucleus 2010 there was The no second increase wave in beganthe incidence in 2010, of with death a rapidfrom accumbens dopamine output is governed by prefrontal cortex. J 10. commonly prescribed opioids. Neurosci. 2001; 21: 676-681. Belujon P, Grace AA. Hippocampus, amygdala and stress: interacting WAVE 3: systems that affect susceptibility to addiction. Ann N Y Acad Sci. 2011; 11. 1216: 114-121. The third wave began in 2013, with a Tzschentke TM. The medial prefrontal cortex as a part of the brain significant increase in overdose deaths due to synthetic 12. reward system. Amino Acids. 2000; 19: 211-219. opioids, particularly involving illicitly manufactured Nestler EJ. The neurobiology of cocaine addiction. Sci Pract Perspect. usuallyfentanyl, unknown and of further to purchasing concern addicts a combination21. of fentanyl 13. 2005; 3: 4-10. with heroin, cocaine, and other counterfeit medications, While the biology of addiction provides insight into Walters CL, Kuo YC, Blendy JA. Differential distribution of CREB in the mesolimbic dopamine reward pathway. J Neurochem. 2003; 87: 1237- 1244. public health problem22. A recent report noted geographic a complex problem, addiction to opioids is a social and 14. Nestler EJ, Barrot M, Self DW. Delta FosB: A sustained molecular 15. switch for addiction. Proc Nat Acad Sci. 2001; 98: 11042-11046. 16. ofvariation the possibility in opioid prescribingof under-treatment in the United of patientsStates, raising with Nestler EJ. Genes and addiction. Nature Genetics. 2000; 26: 277-281. questions about opioid prescribing practices, and warned Bevilacqua L, Goldman D. Genes and addictions. Clin Pharmacol Ther. 17. noted in their study23. In the effort to manage appropriate 2009; 85: 359-361. prescribinglegitimate need there to manageare legal pain, issues versus that the willoverprescribing impact the Goldstein A. Addiction: from Biology to Drug Policy. 2 nd edition 2001 18. prescribing physician Oxford University Press. 24 https://www.cdc.gov/injury/features/prescription-drug-overdose/ 19. Monitoring pain25 in clinical practice index.html overdose-death-rates andis difficult, multi-professional and there engagementis concern aboutwill be using required patient of https://www.drugabuse.gov/related-topics/trends-statistics/ satisfaction as a proxy for quality care . Multidisciplinary 20. federal and state