Accurate Education – Reward Deficiency Syndrome (RDS) & Chronic Pain

Reward Deficiency Syndrome (RDS) & Chronic Pain

While Reward Deficiency Syndrome (RDS) is the common denominator underlying chemical & behavioral addictions and compulsive disorders, it also overlaps with and influences chronic pain. Understanding RDS is important in understanding both the assessment and the treatment of chronic pain.

 

See:

Reward Deficiency Syndrome (RDS)

Reward Deficiency Syndrome (RDS) & Addiction

Genetic Testing: Reward Deficiency Syndrome

Genetic Testing: Individual DNA Alleles

 

See also:

SynaptaGenX

Dopamine Diet

Dopamine Enhancement

Definitions and Terms Related to Pain

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Reward Deficiency Syndrome (RDS) & Chronic Pain

“Reward Deficiency Syndrome (RDS)”
Inadequate levels of dopamine in the reward centers of the brain due to genetic or environmental circumstances leads to an impaired sense of well-being. This condition of sub-optimal dopamine is the basis of the “Reward Deficiency Syndrome.”
See first: Reward Deficiency Syndrome (RDS)

 

Understanding the roles that RDS plays in the management of chronic pain stems from two perspectives:
1. Enhancing Pain Management and Reducing Suffering
2. Identifying and Managing Addiction Risk

1. Enhancing Pain Management and Reducing Suffering

The final experience and measure of suffering as related to pain is linked to the reward pathways in the brain involved with pleasure, emotion, mood and motivation. Factors that impair these reward pathways can prevent recovery from pain or significantly reduce the effectiveness of treatment for pain. Furthermore, chronic pain can impair the reward pathways. Prolonged, recurrent acute pain episodes which lead to chronic pain result in the endogenous pain relief pathways in the reward system to be overwhelmed and insufficient to provide adequate pain relief. This in turn leads to increased stress due to overload of the stress aversion pathways.

 

Stress, including sleep deprivation, emotional and affective disorders (e.g., anxiety, depression) and cognitive deficits (e.g., memory impairment) are among the factors that contribute further to dysfunction of the reward pathways creating the stage for a vicious cycle of pain and stress.

 

The major neurotransmitters involved in the reward pathways include dopamine, serotonin, GABA and the brain’s endogenous opioids, including enkephalins. Variables that affect the manufacture, distribution and breakdown of these neurotransmitters impact both the experience of reward and well-being as well as the nature of the pain experience. For example, drugs that enhance dopamine levels in this area of the brain reduce pain and also enhance perception of reward. This is typified by opioids, cocaine and amphetamines which suppress pain but are also strongly rewarding, contributing to a drive to repeat their use. Eating, especially sweets, is a natural behavior that elevates dopamine and enhances reward and is therefore often used as a coping mechanism for those with pain or chronic stress.

 

A motivational role of dopamine in pain modulation, either to avoid or endure pain has also been identified. Depending on the circumstances, dopamine mediates the motivation to avoid or endure pain in exchange for a greater reward. In another study it was suggested that alterations of dopamine levels in normal physiological ranges do not have measurable effects on pain perception and no direct anti-nociceptive effects. Instead, dopamine’s role in the processing of nociceptive stimuli is through influences on pain salience and coping responses. These propositions indicate that the dopamine system carries subjective value of aversive stimuli, including emotional and physical pain.

 

Glia Cells and the Mesolimbic Dopamine System
The specifics of how chronic pain affects the mesolimbic dopamine (DA) system is not fully understood, but there is new evidence for a role of altered DA signaling, not only in the chronicity of pain, but also in its response to opioid drugs. This evidence suggests a mechanism in which chronic pain activates microglia in the VTA to inhibit DA transmission and disrupt reward behaviors by disrupting Cl homeostasis in GABAergic neurons.This microglial activation is a critical component modulating reward behavior in chronic pain. Activation of microglia and also mast cells, both elements of an inflammatory process involving the nervous system is described as “neuroinflammation.” The process of neuroinflammation is understood to be the basis of the chronification of pain, overlapping with that of RDS.

 

Treating neuroinflammation by inhibiting microglial activation restores normal DA signaling and reward behavior and may be an effective strategy for restoring disrupted DA transmission in RDS as well as disorders linked to RDS such as depression and addiction. Microglial inhibitors such as minocycline, palmitoylethanolamide (PEA) and others are being explored and demonstrating promise as effective agents for treating chronic pain.
See:

Neuroinflammation

Reward Deficiency Syndrome

Genetic Testing: Reward Deficiency Syndrome

Genetic Variants and and Their Impact on Pain

Dopamine functions as a neurotransmitter that activates 5 receptors in the brain, known as dopamine receptors D1 through D5. Research indicates that one receptor in particular, the D2 receptor, is of particular importance in achieving pleasure and reward. The number and availability of the D2 receptors play a role in both reward and pain are influenced by genetic, stress, mood and emotional factors.The low dopamine function in the reward areas of the brain associated with RDS predispose individuals to low pain tolerance. Additionally, it has been shown that stress also reduces dopamine activity in the reward centers and results in hyperalgesia and increased sensitivity to pain. The vicious cycle of chronic pain and stress strongly argues for the potential benefit of treating chronic pain with substances and activities that enhance dopamine in the reward centers.

 

Genetic variants are known to impact the reward pathways. These genetic variations can contribute to impairment of dopamine function in the reward pathways via a number of mechanisms including enhanced breakdown of dopamine and reduction In the number of dopamine receptors necessary for dopamine actions or effects. Genetic variants leading to a deficit of COMT or MAO enzymes that metabolize dopamine may result in excessive tonic dopamine levels that are sufficient to engage feedback by dopamine receptors (D2-autoreceptors) and reduce phasic dopamine release resulting in reduced experience of pleasure and reward. Over time, this may lead to a reward deficit state that accentuates chronic pain and associated symptoms including reduced interest in naturally rewarding stimuli and depression.

 

The naturally occurring endorphin opioids (and exogenous opioids) bind with mu-opioid receptors (such as OPRM1) in the pituitary gland and hypothalamus and can produce a pleasure state through facilitation of dopamine release in the VTA and NAc. Over time, chronic release of endorphins related to pain or exposure to opioids results in down-regulation of the dopamine system and dysregulation of mu-opioid receptors. Genetic variants in the OPRM1 receptor impact this process.

 

Glutamatergic (excitatory) and GABAergic (inhibitory) mechanisms within the reward system have also been studied. Dysregulation of these mechanisms can lead to disruption of dopamine levels. Glutamatergic activity is increased and sensitized during pain chronification. Additionally, increases in GABA activity can block pain signals from reaching the reward center. These mechanisms can eventually lead to increased pain. Again, genetic variants have been identified that impact these factors.

 

Genetic Addiction Risk Score (GARS)

The best way to evaluate an individual for these genetic variants is the use of the saliva-based GARS panel of DNA tests. The GARS also evaluates genetic associations with opioid analgesic requirements for acute and chronic pain states, as well as sensitivity to pain. Knowledge of these findings may facilitate better choices in pain management.

 

For example, it has been shown that individuals with a reduced number of dopamine D2 receptors as identified by the GARS panel have an impaired ability to cope with stress. Dopamine agonist medications that specifically activate dopamine D2 receptors in the reward center inhibit inflammatory pain. Dopamine depletion associated with chronic pain and stress, especially in those with genetic-associated reduction of D2 receptors, has been shown to be responsive to L-tyrosine, a dopamine precursor amino acid supplement. Another means of enhancing dopamine in the reward center is to increase endogenous opioids (enkephalins) with the supplemental use of d-phenylalanine, an enkephalinase inhibitor, which results in increased dopamine. These pharmacological manipulations achieved with the use of dietary supplements such as SynaptaGenX that are designed to up-regulate dopaminergic pathways can lead to reduced pain and stress.

It has been shown that dopamine agonist medications that specifically activate dopamine D2 receptors in the NAc inhibit inflammatory pain and involves mu-opioid receptor interaction as well. The number and availability of these D2 receptors which play a role in both reward and pain are influenced by genetic, stress, mood and emotional factors. It follows that low dopamine function in the reward areas of the brain may predispose individuals to low pain tolerance. Current research supports this concept suggesting that chronic pain patients who are carriers of the D2 TaqA1 allele, which is associated with a reduced number of D2 receptors, may be good candidates for nutrients or bioactive substances designed to enhance dopamine availability in the NAc.

Thus, the treatment of chronic pain should not only target those sensory pain pathways responsive to analgesic medications, but also the reward pathways that mediate affect, mood and salience (i.e., motivation and desire for rewarding stimuli and emotional significance). Knowledge of an individual’s reward pathways and balancing dopamine tone is important in reducing pain suffering and enhancing the sense of well-being.

 

Chronic pain patients with established diagnoses of RDS syndromes, especially those testing positive for significant genetic variants associated with impaired dopamine regulation should consider a trial of nutrition-based dopamine agonist therapy as a means of reducing the degree to which they suffer from their pain. The decision as to which dietary changes or supplements to engage should be based on medical history, genetic testing such as the GARS, and physician guidance.
See:
The Neurobiology of Pain
Genetic Testing: Reward Deficiency Syndrome (RDS)
SynaptaGenX

 

2. Identifying and Managing Addiction Risk

 
In the decision-making process regarding the use of opioids for chronic pain, it is valuable to understand an individual’s risk for developing an abusive or addictive relationship with opioids. Understanding if a person has, or is at risk to develop, an RDS condition allows for more informed decision-making in the choices of opioids and the monitoring of opioid use. No one, the patient nor the physician, wishes to add the burden of addiction to an already compromising condition of chronic pain.

 

Evaluating for RDS risk is best done with genetic testing through use of the saliva-based GARS panel of DNA tests. The GARS panel identifies specific vulnerabilities relative to specific RDS conditions, including impulse disorders and addiction risk to specific drugs and alcohol. This in turn also allows for the use of personalized “nutrigenomic” supplements based on the individual’s genetic profile that can reduce the symptoms or risks of these conditions.

 

While not directly related to RDS, other genetic testing can be useful in managing pain, anxiety and depression. These tests include those that evaluate for genetic variants of enzymes found in the liver, brain and gut. These genetic variants may determine an individual’s response to, and effectiveness of, medications including opioids, anxiolytics and antidepressants based on if they are metabolized quickly, normally, slowly or not at all. Other genetic tests evaluate an individual’s ability to manufacture neurotransmitters such as the test for MTHFR and serotonin production. New tests are becoming available that purport to evaluate an individual’s response to cannabinoids for medical use. (See genetic testing, coming soon).
See: Reward Deficiency Syndrome: Addiction

 

For more in-depth understanding of RDS and pain…

RDS – Overview

1. The Addictive Brain – All Roads Lead to Dopamine – 2012
2. Hatching the behavioral addiction egg – Reward Deficiency Solution System – 2014
3. Sex, Drugs, and Rock ‘N’ Roll – Hypothesizing Common Mesolimbic Activation as a Function of Reward Gene Polymorphisms – 2012
4. “Dopamine homeostasis” requires balanced polypharmacy – Issue with destructive, powerful dopamine agents to combat America’s drug epidemic
5. Neurodynamics of relapse prevention-neuronutrient approach to outpatient DUI offenders
6. Genetic Addiction Risk Testing Coupled with Pro Dopamine Homeostasis
7. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD
8. Neuro-Nutrient Effects on Weight Loss in Carbohydrate Bingers – an open clinical trial
9. Enkephalinase Inhibition – Regulation of Ethanol Intake in Genetically Predisposed Mice
10. The D2 dopamine receptor gene as a determinant of reward deficiency syndrome – 1996
11. Dopamine D2 receptor gene variants: association and linkage studies in impulsive-addictive-compulsive behaviour. – PubMed – NCBI
12. Activation instead of blocking mesolimbic dopaminergic reward circuitry is a preferred modality in the long term treatment of reward deficiency syndrome (RDS) – a commentary – 2008
13. Reward deficiency syndrome: a biogenetic model for the diagnosis and treatment of impulsive, addictive, and compulsive behaviors. – PubMed – NCBI
14. Association of polymorphisms of dopamine D2 receptor (DRD2), and dopamine transporter (DAT1) genes with schizoid:avoidant behaviors (SAB). – PubMed – NCBI
15. Reward deficiency syndrome: genetic aspects of behavioral disorders. – PubMed – NCBI
16. The D2 dopamine receptor gene as a predictor of compulsive disease: Bayes’ theorem. – PubMed – NCBI
17. Delayed P300 latency correlates with abnormal Test of Variables of Attention (TOVA) in adults and predicts early cognitive decline in a clinical se… – PubMed – NCBI

RDS – ADD

1. Attention-deficit-hyperactivity disorder and reward deficiency syndrome – 2008
2. Reward Deficiency Syndrome – Attentional Arousal Subtypes, Limitations of Current Diagnostic Nosology, and Future Research – 2015
3. Neurogenetic interactions and aberrant behavioral co-morbidity of attention deficit hyperactivity disorder (ADHD) -dispelling myths – 2005
4. Epigenetics in Developmental Disorder – ADHD and Endophenotypes
5. Low Dopamine Function in Attention Deficit:Hyperactivity Disorder – Should Genotyping Signify Early Diagnosis in Children? – 2014
6. Enhancement of attention processing by Kantroll in healthy humans: a pilot study. – PubMed – NCBI
7. Pro-dopamine regulator, KB220Z, attenuates hoarding and shopping behavior in a female, diagnosed with SUD and ADHD

RDS – Exercise

1. Physical Exercise Interventions for Drug Addictive Disorders – 2017
2. Basal ganglia dysfunction contributes to physical inactivity in obesity – 2017
3. Running from Disease – Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes – 2017

RDS – Gaming

1. linking-online-gaming-and-addictive-behavior-converging-evidence-for-a-general-reward-deficiency-in-frequent-online-gamers-2014

 

RDS – Genetics

1. Multilocus Genetic Composite Reflecting Dopamine Signaling Capacity Predicts Reward Circuitry Responsivity 2012
2. Genetic Addiction Risk Score (GARS) – Testing For Polygenetic Predisposition and Risk to Reward Deficiency Syndrome (RDS) – 2011
3. Neurogenetic Impairments of Brain Reward Circuitry Links to Reward Deficiency Syndrome (RDS) – Potential Nutrigenomic Induced Dopaminergic Activation

RDS – Obesity

1. Reward Deficiency Syndrome Studies of KB220 Variants
2. Mood, food, and obesity
3. Dopamine and glucose, obesity, and reward deficiency syndrome – 2014
4. Dopamine for “wanting” and opioids for “liking”: a comparison of obese adults with and without binge eating. – PubMed – NCBI
5. “Liking” and “Wanting” Linked to Reward Deficiency Syndrome (RDS) – Hypothesizing Differential Responsivity in Brain Reward Circuitry – 2012
6. Neuro-Genetics of Reward Deficiency Syndrome (RDS) as the Root Cause of “Addiction Transfer”- 2011
7. Physical Exercise Interventions for Drug Addictive Disorders – 2017
8. Basal ganglia dysfunction contributes to physical inactivity in obesity – 2017
9. Running from Disease – Molecular Mechanisms Associating Dopamine and Leptin Signaling in the Brain with Physical Inactivity, Obesity, and Type 2 Diabetes – 2017
10. Incorporating food addiction into disordered eating – the disordered eating food addiction nutrition guide (DEFANG) – 2017
11. Do Dopaminergic Impairments Underlie Physical Inactivity in People with Obesity? – 2016
12. Pilot clinical observations between food and drug seeking derived from fifty cases attending an eating disorder clinic – 2016
13. A meta-analysis of the relationship between brain dopamine receptors and obesity – a matter of changes in behavior rather than food addiction? – 2016
14. Increasing dopamine D2 receptor expression in the adult nucleus accumbens enhances motivation – 2013
15. Food restriction markedly increases dopamine D2 receptor (D2R) in a rat model of obesity as assessed with in-vivo muPET imaging ([11C] raclopride) … – PubMed – NCBI
16. LOW DOPAMINE D2 RECEPTOR INCREASES VULNERABILITY TO OBESITY VIA REDUCED PHYSICAL ACTIVITY NOT INCREASED APPETITIVE MOTIVATION – 2016
17. Dopamine and glucose, obesity, and reward deficiency syndrome – 2014
18. Food Addiction, High-Glycemic-Index Carbohydrates, and Obesity. – PubMed – NCBI – 2018
19. Association of dopamine D2 receptor and leptin receptor genes with clinically severe obesity. – PubMed – NCBI
20. LG839: anti-obesity effects and polymorphic gene correlates of reward deficiency syndrome. – PubMed – NCBI

 

RDS – Chronic Pain

1. Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic – 2009
2. A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain – 2014
3. Love as a Modulator of Pain – 2017
4. Comorbidity of alcohol use disorder and chronic pain – Genetic influences on brain reward and stress systems – 2017
5. Reward Circuitry Plasticity in Pain Perception and Modulation – 2017
6. Modulation of pain, nociception, and analgesia by the brain reward center – 2016
7. Pharmacology of enkephalinase inhibitors: animal and human studies. – PubMed – NCBI 198
8. Analgesic properties of enkephalinase inhibitors: animal and human studies. – PubMed – NCBI 1985
9. DL-phenylalanine markedly potentiates opiate analgesia – an example of nutrient:pharmaceutical up-regulation of the endogenous analgesia system. – PubMed – NCBI – 2000
10. Iatrogenic opioid dependence is endemic and legal – Genetic addiction risk score (GARS) with electrotherapy a paradigm shift in pain treatment programs – 2013
11. Mesolimbic dopamine signaling in acute and chronic pain – implications for motivation, analgesia, and addiction – 2016
12. Microglia Disrupt Mesolimbic Reward Circuitry in Chronic Pain Positive emotions and brain reward circuits in chronic pain – 2016
13. The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain – 2016
14. Dopamine and Pain Sensitivity – Neither Sulpiride nor Acute Phenylalanine and Tyrosine Depletion Have Effects on Thermal Pain Sensations in Healthy Volunteers – 2013
15. Dopamine Precursor Depletion Influences Pain Affect Rather than Pain Sensation – 2014
16. Insurance Companies Fighting the Peer Review Empire without any Validity – 2018
17. Modulation of pain, nociception, and analgesia by the brain reward center – 2016
18. Mesolimbic dopamine signaling in acute and chronic pain – implications for motivation, analgesia, and addiction – 2016
19. The risk for problematic opioid use in chronic pain: What can we learn from studies of pain and reward? – PubMed – NCBI
20. Reward Circuitry Plasticity in Pain Perception and Modulation – 2017

 

RDS – PTSD

1. Neuro-psychopharmacogenetics and Neurological Antecedents of Posttraumatic Stress Disorder – Unlocking the Mysteries of Resilience and Vulnerability – 2010
2. Diagnosis and Healing In Veterans Suspected of Suffering from Post-Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and RewardCircuitry Natural Dopaminergic Activation-2012
3. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients – Role of enhanced brain reward functional connectivity and homeostasis redeeming joy – 2015

RDS – Sleep

1. Dopaminergic Neurogenetics of Sleep Disorders in Reward Deficiency Syndrome (RDS) – 2014

 

RDS – Treatment

RDS Treatment – Overview

1. Clinically Combating Reward Deficiency Syndrome (RDS) with Dopamine Agonist Therapy as a Paradigm Shift – Dopamine for Dinner? 2015
2. Neurogenetics and Nutrigenomics of Neuro-Nutrient Therapy for Reward Deficiency Syndrome (RDS)

RDS Treatment – Meditation

1. Increased dopamine tone during meditation-induced change of conscio… – PubMed – NCBI

RDS Treatment – Music Therapy

1. Do dopaminergic gene polymorphisms affect mesolimbic reward activat… – PubMed – NCBI

RDS Treatment – SynaptaGenX

SynaptaGenX – Overviews

1. Synaptamine – brief summary

SynaptaGenX – Buprenorphine

1. Withdrawal from Buprenorphine:Naloxone and Maintenance with a Natural Dopaminergic Agonist – A Cautionary Note

SynaptaGenX – Fibromyalgia

1. A Multi-Locus Approach to Treating Fibromyalgia by Boosting Dopaminergic Activity in the Meso-Limbic System of the Brain

 

SynaptaGenX – Lucid Nightmares

1. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients – Role of enhanced brain reward functional connectivity and homeostasis redeeming joy – 2015
2. Using the Neuroadaptagen KB200zTM to Ameliorate Terrifying, Lucid Nightmares in RDS Patients – the Role of Enhanced, Brain- Reward, Functional Connectivity and Dopaminergic Homeostasis – 2015

SynaptaGenX – PTSD

1. Putative dopamine agonist (KB220Z) attenuates lucid nightmares in PTSD patients – Role of enhanced brain reward functional connectivity and homeostasis redeeming joy – 2015
2. Diagnosis and Healing In Veterans Suspected of Suffering from Post-Traumatic Stress Disorder (PTSD) Using Reward Gene Testing and RewardCircuitry Natural Dopaminergic Activation-2012

SynaptaGenX – Sleep

1. hypothesizing-that-putative-dopaminergic-melatonin-benzodiazepine-reward-circuitry-receptors – 2013

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