Hypothesizing that brain reward circuitry genes are genetic antecedents of pain sensitivity and critical diagnostic and pharmacogenomic treatment targets for chronic pain conditions
Open accessAbstract
While it is well established that the principal ascending pathways for pain originate in the dorsal horn of the spinal cord and in the medulla, the control and sensitivity to pain may reside in additional neurological loci, especially in the mesolimbic system of the brain (i.e., a reward center), and a number of genes and associated polymorphisms may indeed impact pain tolerance and or sensitivity. It is hypothesized that these polymorphisms associate with a predisposition to intolerance or tolerance to pain. It is further hypothesized that identification of certain gene polymorphisms provides a unique therapeutic target to assist in the treatment of pain. It is hereby proposed that pharmacogenetic testing of certain candidate genes (i.e., mu receptors, PENK etc.) will result in pharmacogenomic solutions personalized to the individual patient, with potential improvement in clinical outcomes.
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Variability in the mesolimbic system, due to genetic polymorphisms, may predispose individuals to heightened pain sensitivity or enhanced tolerance.
“Variability in the mesolimbic system, due to genetic polymorphisms, may predispose individuals to heightened pain sensitivity or enhanced tolerance.27”
From Beyond Stigma–Integrating Neurobiology, Genetics, and Awareness Integration Theory in Addiction Recovery (2026) · cites this paper as [27]
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References 45 · Cited by 84
- Authors
- Chen, A. L.-C., Chen, T. J. H., Waite, R. L., Reinking, J., Tung, H. L., Rhoades, P., Downs, B. W., Braverman, E., Braverman, D., Kerner, M., Blum, S. H., DiNubile, N., Smith, D., Oscar-Berman, M., Prihoda, T. J., Floyd, J. B., O’Brien, D., Liu, H. H., & Blum, K.
- Affiliations
- Chang Jung Christian University (TW)
- Changhua Christian Hospital (TW)
- University of California, Davis (US)
- University of California System (US)
- Edisto Island Historic Preservation Society (US)
- Weill Cornell Medicine (US)
- Hospital of the University of Pennsylvania (US)
- The University of Texas at San Antonio Health Science Center (US)
- Chung Shan Medical University (TW)
- Corresponding author
- Liu, H.H.
- Blum, Kenneth
- Venue
- Medical Hypotheses
- Publisher
- Elsevier BV
- Published
- 2009-01
- Volume
- 72
- Issue
- 1
- Pages
- 14-22
- ISSN
- 0306-9877 (ISSN-L)
- PMC
- PMC4098664
- OpenAlex
- W2067997608
- Cited by
- 84
- References
- 45
- Citations by year
- 2026: 1 · 2025: 2 · 2024: 2 · 2023: 2 · 2022: 5 · 2021: 4 · 2020: 44 · 2018: 2 · 2017: 1 · 2015: 2 · 2014: 4 · 2013: 5 · 2012: 2
- FWCI
- 0.29
- Type
- journal article
- Language
- en
- Open access
- green
- www.ncbi.nlm.nih.gov
- Locations
- Medical Hypotheses (publishedVersion)
- PubMed (publishedVersion)
- Europe PMC (PubMed Central) (acceptedVersion)
- PubMed Central (acceptedVersion)
- Funders
- National Institute on Alcohol Abuse and Alcoholism (R01AA007112, K05AA000219)
- Topics
- Health Sciences › Medicine › Physiology › Pain Mechanisms and Treatments
- Health Sciences › Medicine › Anesthesiology and Pain Medicine › Pain Management and Opioid Use
- Life Sciences › Pharmacology, Toxicology and Pharmaceutics › Pharmacology › Pharmacogenetics and Drug Metabolism
- Keywords
- chronic pain, pain sensitivity, brain reward system, mesolimbic system, genetic polymorphism, pharmacogenomics, personalized medicine, mu-opioid receptor, proenkephalin, pain tolerance
- MeSH terms
- Afferent Pathways, Analgesics, Brain, Dopamine, Fibromyalgia, Humans, Morphine, Neurons, Nociceptors, Pain, Reward, Spinal Cord, Stress, Psychological, Pain Threshold, Substance-Related Disorders
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