Bridging the genetic gulf: a deep dive into neurotransmission, pharmacogenomics, and genetic variations for optimal pain management

Authors

  • Jaeyres Jani Borneo Medical and Health Research Centre, Faculty of Medicine and Health Sciences, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia
  • Constance Liew Sat Lin Department of Anaesthesiology and Intensive Care, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia
  • D. Kamarudin D. Mudin Department of Anaesthesiology and Intensive Care, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia
  • Rajesh Kumar Muniandy Department of Anaesthesiology and Intensive Care, Faculty of Medicine and Health Science, Universiti Malaysia Sabah, 88400 Kota Kinabalu, Sabah, Malaysia

DOI:

https://doi.org/10.31117/neuroscirn.v7i2.316

Keywords:

Neurotransmission, Pharmacogenomics, Genetic Variations, Pain Management

Abstract

Pain embodies a complex sensory experience influenced by a medley of biological, psychological, and genetic. Pain perception can be classed into four main categories: nociceptive pain, neuropathic pain, acute pain, and chronic pain. Genetic polymorphisms, which are basically genetic variations in DNA sequences, have a part to play in the neurotransmission pathways associated with pain perception and the ultimate effectiveness of pain management interventions. Learning about the effects of genetics on neurotransmission in pain management offers a fresh viewpoint on individual variations in pain sensitivity, response to treatment, and the development of personalised approaches to pain management. A closer look at the relationship between genetic polymorphisms and neurotransmission provides a better understanding deep down at the genetic level. These chemical messengers, neurotransmitters, help pass signals between nerve cells; they are essential for pain processing and modulation. Differences in genetic makeup in neurotransmitter-related genes could change how these genes express, function, and regulate, thus changing how humans perceive pain and respond to pain management interventions. The conjunction of neurotransmission and pharmacogenomics forms a unique convergence, composing a narrative that discloses the percipient influence of individual genetic differences on neural communication and responses to pharmaceuticals. These genetic variations elaborately construct the molecular architecture supervising neurotransmitter release, receptor interactions, and enzymatic processes within the nervous system. In this review, the convergence of neurotransmission, pharmacogenomics, and genetic variations illuminates a pivotal realm in healthcare.  Genetic variations intricately influence neurotransmission pathways, moulding individual responses to pharmacological interventions.  This intersection not only underscores the complexity of human biology but also holds the promise of personalised healthcare solutions. Recognising subtle genetic variations in neurotransmission and pharmacogenomics opens the door to precision medicine, tailoring treatments to individual genetic codes and revolutionising our approach to medical care.

References

Adam, Y., Samtal, C., Brandenburg, J. T., Falola, O., & Adebiyi, E. (2021). Performing post-genome-wide association study analysis: overview, challenges and recommendations. F1000Research, 10, 1002. https://doi.org/10.12688/f1000research.53962.1

Adewuyi, E. O., O'Brien, E. K., Nyholt, D. R., Porter, T., & Laws, S. M. (2022). A large-scale genome-wide cross-trait analysis reveals shared genetic architecture between Alzheimer's disease and gastrointestinal tract disorders. Communications Biology, 5(1), 691. https://doi.org/10.1038/s42003-022-03607-2

Ahlers, S. J., Elens, L. L., van Gulik, L., van Schaik, R. H., van Dongen, E. P., Bruins, P., Tibboel, D., & Knibbe, C. A. (2013). The Val158Met polymorphism of the COMT gene is associated with increased pain sensitivity in morphine-treated patients undergoing a painful procedure after cardiac surgery. British Journal of Clinical Pharmacology, 75(6), 1506–1515. https://doi.org/10.1111/bcp.12052

Allen, M. J., Sabir, S., & Sharma, S. (2023). GABA Receptor. In Trends in Pharmacological Sciences (Vol. 2, Issue C). StatPearls Publishing. https://doi.org/10.1016/0165-6147(81)90264-9

Anekar, A. A., Hendrix, J. M., & Cascella, M. (2023). WHO Analgesic Ladder. In Journal of the Royal College of Physicians of Edinburgh (Vol. 38, Issue 3). StatPearls Publishing. https://doi.org/10.1007/978-3-642-28753-4_102537

Answine, J.F. (2018). A Basic Review of Pain Pathways and Analgesia. McMahon Publishing. Available from: https://www.anesthesiologynews.com/Review-Articles/Article/10-18/A-Basic-Review-of-Pain-Pathways-and-Analgesia/52868

Barchetta, I., Cimini, F. A., Dule, S., & Cavallo, M. G. (2022). Dipeptidyl Peptidase 4 (DPP4) as A Novel Adipokine: Role in Metabolism and Fat Homeostasis. Biomedicines, 10(9), 2306. https://doi.org/10.3390/biomedicines10092306

Barnes, J., Mondelli, V., & Pariante, C. M. (2017). Genetic Contributions of Inflammation to Depression. Neuropsychopharmacology: official publication of the American College of Neuropsychopharmacology, 42(1), 81–98. https://doi.org/10.1038/npp.2016.169

Baskozos, G., Dawes, J. M., Austin, J. S., Antunes-Martins, A., McDermott, L., Clark, A. J., Trendafilova, T., Lees, J. G., McMahon, S. B., Mogil, J. S., Orengo, C., & Bennett, D. L. (2019). Comprehensive analysis of long noncoding RNA expression in dorsal root ganglion reveals cell-type specificity and dysregulation after nerve injury. Pain, 160(2), 463–485. https://doi.org/10.1097/j.pain.0000000000001416

Bonilla-Jaime, H., Sánchez-Salcedo, J. A., Estévez-Cabrera, M. M., Molina-Jiménez, T., Cortes-Altamirano, J. L., & Alfaro-Rodríguez, A. (2022). Depression and pain: use of antidepressants. Current Neuropharmacology, 20(2), 384–402. https://doi.org/10.2174/1570159x19666210609161447

Bortolato, M., Chen, K., & Shih, J. C. (2008). Monoamine oxidase inactivation: from pathophysiology to therapeutics. Advanced Drug Delivery Reviews, 60(13-14), 1527–1533. https://doi.org/10.1016/j.addr.2008.06.002

Brandl, E., Halford, Z., Clark, M. D., & Herndon, C. (2021). Pharmacogenomics in Pain Management: A Review of Relevant Gene-Drug Associations and Clinical Considerations. The Annals of Pharmacotherapy, 55(12), 1486–1501. https://doi.org/10.1177/10600280211003875

Bright, D. R., Petry, N., Roath, E., & Gibb, T. (2021). Engaging pharmacogenomics in pain management and opioid selection. Pharmacogenomics, 22(14), 927–937. https://doi.org/10.2217/pgs-2021-0044

Bugada, D., Lorini, F. L., Fumagalli, R., & Allegri, M. (2020). Genetics and Opioids: towards more appropriate prescription in cancer pain. Cancers, 12(7), 1951. https://doi.org/10.3390/cancers12071951

Chadwick, A., Frazier, A., Khan, T. W., & Young, E. (2021). Understanding the Psychological, Physiological, and Genetic Factors Affecting Precision Pain Medicine: A Narrative Review. Journal of Pain Research, 14, 3145–3161. https://doi.org/10.2147/JPR.S320863

Chadwick, P., Hughes, S., Russell, D., Russell, I., & Dagnan, D. (2009). Mindfulness groups for distressing voices and paranoia: A replication and Randomized feasibility trial. Behavioural and Cognitive Psychotherapy, 37(4), 403–412. https://doi.org/10.1017/s1352465809990166

Chang, M., He, L., & Cai, L. (2018). An Overview of Genome-Wide Association Studies. In Methods in Molecular Biology (Vol. 1754, pp. 97–108). Humana Press, New York. https://doi.org/10.1007/978-1-4939-7717-8_6

Correia, A. S., Cardoso, A., & Vale, N. (2023). BDNF unveiled: Exploring its role in major depression disorder serotonergic imbalance and associated stress conditions. Pharmaceutics, 15(8), 2081. https://doi.org/10.3390/pharmaceutics15082081

Crews, K. R., Monte, A. A., Huddart, R., Caudle, K. E., Kharasch, E. D., Gaedigk, A., Dunnenberger, H. M., Leeder, J. S., Callaghan, J. T., Samer, C. F., Klein, T. E., Haidar, C. E., Van Driest, S. L., Ruaño, G., Sangkuhl, K., Cavallari, L. H., Müller, D. J., Prows, C. A., Nagy, M., & Skaar, T. C. (2021). Clinical Pharmacogenetics Implementation Consortium Guideline for CYP2D6, OPRM1, and COMT genotypes and select opioid therapy. Clinical Pharmacology & Therapeutics, 110(4), 888–896. https://doi.org/10.1002/cpt.2149

De Leon, A. S., & Tadi, P. (2023). Biochemistry, Gamma Aminobutyric Acid. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK551683/

Dowell, D., Ragan, K., Jones, C. M., Baldwin, G. T., & Chou, R. (2022). CDC Clinical Practice Guideline for Prescribing Opioids for Pain—United States, 2022. Morbidity and Mortality Weekly Report, 71(3), 1–95. https://doi.org/10.15585/mmwr.rr7103a1

El-Tallawy, S. N., Nalamasu, R., Salem, G. I., LeQuang, J. A., Pergolizzi, J. V., & Christo, P. J. (2021). Management of Musculoskeletal Pain: An Update with Emphasis on Chronic Musculoskeletal Pain. Pain and Therapy, 10(1), 181–209. https://doi.org/10.1007/s40122-021-00235-2

Forster, J. L., Duis, J., & Butler, M. G. (2021). Pharmacogenetic Testing of Cytochrome P450 Drug Metabolizing Enzymes in a Case Series of Patients with Prader-Willi Syndrome. Genes, 12(2), 152. https://doi.org/10.3390/genes12020152

Gaedigk, A., Whirl-Carrillo, M., Pratt, V. M., Miller, N. A., & Klein, T. E. (2020). PharmVar and the Landscape of Pharmacogenetic Resources. Clinical Pharmacology and Therapeutics, 107(1), 43–46. https://doi.org/10.1002/cpt.1654

Gilbert, D. G., Zuo, Y., Rabinovich, N. E., Riise, H., Needham, R., & Huggenvik, J. I. (2009). Neurotransmission-related genetic polymorphisms, negative affectivity traits, and gender predict tobacco abstinence symptoms across 44 days with and without nicotine patch. Journal of Abnormal Psychology, 118(2), 322–334. https://doi.org/10.1037/a0015382

Gupta, S., & Sen, U. (2019). More than just an enzyme: Dipeptidyl peptidase-4 (DPP-4) and its association with diabetic kidney remodelling. Pharmacological Research, 147, 104391. https://doi.org/10.1016/j.phrs.2019.104391

Habehh, H., & Gohel, S. (2021). Machine Learning in Healthcare. Current Genomics, 22(4), 291–300. https://doi.org/10.2174/1389202922666210705124359

Herman, T. F., Cascella, M., & Muzio, M. R. (2023). Mu Receptors. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK551554/

Hussein D. (2023). In Silico Investigation of the Human GTP Cyclohydrolase 1 Enzyme Reveals the Potential of Drug Repurposing Approaches towards the Discovery of Effective BH4 Therapeutics. International Journal of Molecular Sciences, 24(2), 1210. https://doi.org/10.3390/ijms24021210

Idda, M. L., Zoledziewska, M., Urru, S. A. M., McInnes, G., Bilotta, A., Nuvoli, V., Lodde, V., Orrù, S., Schlessinger, D., Cucca, F., & Floris, M. (2022). Genetic Variation among Pharmacogenes in the Sardinian Population. International Journal of Molecular Sciences, 23(17), 10058. https://doi.org/10.3390/ijms231710058

James S. (2013). Human pain and genetics: some basics. British Journal of Pain, 7(4), 171–178. https://doi.org/10.1177/2049463713506408

Ji, F., & Sadreyev, R. I. (2018). RNA-seq: Basic Bioinformatics Analysis. Current Protocols in Molecular Biology, 124(1), e68. https://doi.org/10.1002/cpmb.68

Kaye, A. D., Garcia, A. J., Hall, O. M., Jeha, G. M., Cramer, K. D., Granier, A. L., Kallurkar, A., Cornett, E. M., & Urman, R. D. (2019). Update on the pharmacogenomics of pain management. Pharmacogenomics and Personalized Medicine, 12, 125–143. https://doi.org/10.2147/PGPM.S179152

Kaye, A. D., Garcia, A., Hall, O. M., Jeha, G. M., Cramer, K. D., Granier, A. L., Kallurkar, A., Cornett, E. M., & Urman, R. D. (2019). Update on the pharmacogenomics of pain management. Pharmacogenomics and Personalized Medicine, 12, 125–143. https://doi.org/10.2147/pgpm.s179152

Kerpagam, S.R.N., Usha, S.R., Kumaravadivel, T.D. & Muniandy, R.K. (2023). Medication Compliance of Patients Attending a Pain Clinic at a Tertiary Hospital in Malaysia. Borneo Journal of Medical Sciences, 17(2), 18–24. https://doi.org/10.51200/bjms.v17i2.3884

Kim, H., Clark, D., & Dionne, R. A. (2009). Genetic contributions to clinical pain and analgesia: avoiding pitfalls in genetic research. The Journal of Pain, 10(7), 663–693. https://doi.org/10.1016/j.jpain.2009.04.001

Knezevic, N. N., Tverdohleb, T., Knezevic, I., & Candido, K. D. (2018). The Role of Genetic Polymorphisms in Chronic Pain Patients. International Journal of Molecular Sciences, 19(6), 1707. https://doi.org/10.3390/ijms19061707

Latremoliere, A., & Costigan, M. (2011). GCH1, BH4 and pain. Current Pharmaceutical Biotechnology, 12(10), 1728–1741. https://doi.org/10.2174/138920111798357393

Latremoliere, A., Latini, A., Andrews, N., Cronin, S. J., Fujita, M., Gorska, K., Hovius, R., Romero, C., Chuaiphichai, S., Painter, M., Miracca, G., Babaniyi, O., Remor, A. P., Duong, K., Riva, P., Barrett, L. B., Ferreirós, N., Naylor, A., Penninger, J. M., Tegeder, I., Zhong J., Blagg J., Channon K. M., Johnsson K., Costigan M., Woolf, C. J. (2015). Reduction of Neuropathic and Inflammatory Pain through Inhibition of the Tetrahydrobiopterin Pathway. Neuron, 86(6), 1393–1406. https://doi.org/10.1016/j.neuron.2015.05.033

Ma, G., Fan, H., Shen, C., & Wang, W. (2016). Genetic and Neuroimaging Features of Personality Disorders: State of the Art. Neuroscience Bulletin, 32(3), 286–306. https://doi.org/10.1007/s12264-016-0027-8

Mackey S. (2016). Future Directions for Pain Management: Lessons from the Institute of Medicine Pain Report and the National Pain Strategy. Hand Clinics, 32(1), 91–98. https://doi.org/10.1016/j.hcl.2015.08.012

Majeed, M. H., Ubaidulhaq, M., Rugnath, A., & Eriator, I. (2018). Extreme Ends of Pain Sensitivity in SCN9A Mutation Variants: Case Report and Literature Review. Innovations in Clinical Neuroscience, 15(11-12), 33–35.

Manzoni, C., Kia, D. A., Vandrovcova, J., Hardy, J., Wood, N. W., Lewis, P. A., & Ferrari, R. (2018). Genome, transcriptome and proteome: the rise of omics data and their integration in biomedical sciences. Briefings in Bioinformatics, 19(2), 286–302. https://doi.org/10.1093/bib/bbw114

Marcianò, G., Vocca, C., Evangelista, M., Palleria, C., Gallelli, L., Galati, C., Monea, F., Sportiello, L., De Sarro, G., Capuano, A., & Gallelli, L. (2023). The Pharmacological Treatment of Chronic Pain: From guidelines to daily clinical practice. Pharmaceutics, 15(4), 1165. https://doi.org/10.3390/pharmaceutics15041165

Margoob, M. A., & Mushtaq, D. (2011). Serotonin transporter gene polymorphism and psychiatric disorders: Is there a link? Indian Journal of Psychiatry, 53(4), 289. https://doi.org/10.4103/0019-5545.91901

Margoob, M. A., Mushtaq, D., Murtza, I., Mushtaq, H., & Ali, A. (2008). Serotonin transporter gene polymorphism and treatment response to serotonin reuptake inhibitor (escitalopram) in depression: An open pilot study. Indian Journal of Psychiatry, 50(1), 47. https://doi.org/10.4103/0019-5545.39759

McInnes, G., Lavertu, A., Sangkuhl, K., Klein, T. E., Whirl-Carrillo, M., & Altman, R. B. (2021). Pharmacogenetics at Scale: An Analysis of the UK Biobank. Clinical Pharmacology and Therapeutics, 109(6), 1528–1537. https://doi.org/10.1002/cpt.2122

Micaglio, E., Locati, E. T., Monasky, M. M., Romani, F., Heilbron, F., & Pappone, C. (2021). Role of Pharmacogenetics in Adverse Drug Reactions: An Update towards Personalized Medicine. Frontiers in Pharmacology, 12, 651720. https://doi.org/10.3389/fphar.2021.651720

Mittal, D., Mease, R., Kuner, T., Flor, H., Kuner, R., & Andoh, J. (2022). Data management strategy for a collaborative research center. GigaScience, 12, giad049. https://doi.org/10.1093/gigascience/giad049

Nagatsu T. (2007). The catecholamine system in health and disease - Relation to tyrosine 3-monooxygenase and other catecholamine-synthesizing enzymes. Proceedings of the Japan Academy (Series B): Physical and Biological Sciences, 82(10), 388–415. https://doi.org/10.2183/pjab.82.388

Nahin, R. L., Feinberg, T., Kapos, F. P., & Terman, G. W. (2023). Estimated Rates of Incident and Persistent Chronic Pain Among US Adults, 2019-2020. JAMA Network Open, 6(5), e2313563. https://doi.org/10.1001/jamanetworkopen.2023.13563

Navratilova, E., & Porreca, F. (2019). Substance P and inflammatory pain: getting it wrong and right simultaneously. Neuron, 101(3), 353–355. https://doi.org/10.1016/j.neuron.2019.01.034

Nekovářová, T., Yamamotová, A., Valeš, K., Stuchlı́K, A., Fricová, J., & Rokyta, R. (2014). Common mechanisms of pain and depression: are antidepressants also analgesics? Frontiers in Behavioral Neuroscience, 8, 99. https://doi.org/10.3389/fnbeh.2014.00099

Nyorong, M., Nadapdap, T. P., & Yanthy, L. (2021). Analysis of Factors Associated with Compliance with Taking Medicines for Pulmonary Tuberculosis Patients at Lut Tawar Health Center, Central Aceh Regency. Journal of Asian Multicultural Research for Hedical and Health Science Study, 2(4), 82–94. https://doi.org/10.47616/JAMRMHSS.V2I4.222

Oates, J. T., & Lopez, D. (2018). Pharmacogenetics: An Important Part of Drug Development with A Focus on Its Application. International Journal of Biomedical Investigation, 1(2), 111. https://doi.org/10.31531/2581-4745.1000111

Obata, H. (2017). Analgesic Mechanisms of Antidepressants for Neuropathic Pain. International Journal of Molecular Sciences, 18(11), 2483. https://doi.org/10.3390/ijms18112483

Paredes, S., Cantillo, S., Candido, K. D., & Knezevic, N. N. (2019). An Association of Serotonin with Pain Disorders and Its Modulation by Estrogens. International Journal of Molecular Sciences, 20(22), 5729. https://doi.org/10.3390/ijms20225729

Pathan, H., & Williams, J. (2012). Basic opioid pharmacology: an update. British Journal of Pain, 6(1), 11–16. https://doi.org/10.1177/2049463712438493

Porter, G. A., & O’Connor, J. C. (2022). Brain-derived neurotrophic factor and inflammation in depression: Pathogenic partners in crime? World Journal of Psychiatry, 12(1), 77–97. https://doi.org/10.5498/wjp.v12.i1.77

Prescott, S. A., & Ratté, S. (2017). Somatosensation and pain. In Elsevier eBooks (pp. 517–539). https://doi.org/10.1016/b978-0-12-802381-5.00037-3

Porcelli, S., Drago, A., Fabbri, C., Gibiino, S., Calati, R., & Serretti, A. (2011). Pharmacogenetics of antidepressant response. Journal of Psychiatry & Neuroscience, 36(2), 87–113. https://doi.org/10.1503/jpn.100059

Radosavljević, M., Štrac, D. Š., Jančić, J., & Samardžić, J. (2023). The role of pharmacogenetics in personalizing the antidepressant and anxiolytic therapy. Genes, 14(5), 1095. https://doi.org/10.3390/genes14051095

Raja, K., Patrick, M., Gao, Y., Madu, D., Yang, Y., & Tsoi, L. C. (2017). A Review of Recent Advancement in Integrating Omics Data with Literature Mining towards Biomedical Discoveries. International Journal of Genomics, 2017, 6213474. https://doi.org/10.1155/2017/6213474

Sanchez-Martinez, S., Camara, O., Piella, G., Cikes, M., González-Ballester, M. Á., Miron, M., Vellido, A., Gómez, E., Fraser, A. G., & Bijnens, B. (2022). Machine Learning for Clinical Decision-Making: Challenges and Opportunities in Cardiovascular Imaging. Frontiers in Cardiovascular Medicine, 8, 765693. https://doi.org/10.3389/fcvm.2021.765693

Scarborough, B. M., & Smith, C. B. (2018). Optimal pain management for patients with cancer in the modern era. CA: A Cancer Journal for Clinicians, 68(3), 182–196. https://doi.org/10.3322/caac.21453

Shaw, K., Amstutz, U., & Carleton, B. C. (2011). Using pharmacogenetics to understand adverse drug reactions in children. Paediatrics & Child Health, 16(9), 537–538. https://doi.org/10.1093/pch/16.9.537

Sheng, J., Liu, S., Wang, Y., Cui, R., & Zhang, X. (2017). The Link between Depression and Chronic Pain: Neural Mechanisms in the Brain. Neural Plasticity, 2017, 9724371. https://doi.org/10.1155/2017/9724371

Sprouse-Blum, A. S., Smith, G., Sugai, D., & Parsa, F. D. (2010). Understanding endorphins and their importance in pain management. Hawaii Medical Journal, 69(3), 70–71.

Su, D., Singer, E. A., & Srinivasan, R. (2015). Molecular pathways in renal cell carcinoma: recent advances in genetics and molecular biology. Current Opinion in Oncology, 27(3), 217–223. https://doi.org/10.1097/CCO.0000000000000186

Tanaka, T., Narazaki, M., & Kishimoto, T. (2014). IL-6 in inflammation, immunity, and disease. Cold Spring Harbor Perspectives in Biology, 6(10), a016295. https://doi.org/10.1101/cshperspect.a016295

Tanguay-Sabourin, C., Fillingim, M., Guglietti, G. V., Zare, A., Parisien, M., Norman, J., Sweatman, H., Da-Ano, R., Heikkala, E., PREVENT-AD Research Group, Perez, J., Karppinen, J., Villeneuve, S., Thompson, S. J., Martel, M. O., Roy, M., Diatchenko, L., & Vachon-Presseau, E. (2023). A prognostic risk score for development and spread of chronic pain. Nature Medicine, 29, 1821–1831. https://doi.org/10.1038/s41591-023-02430-4

Taqi, M. M., Faisal, M., & Zaman, H. (2019). OPRM1 A118G Polymorphisms and Its Role in Opioid Addiction: Implication on Severity and Treatment Approaches. Pharmacogenomics and Personalized Medicine, 12, 361–368. https://doi.org/10.2147/PGPM.S198654

Taylor, C., Crosby, I., Yip, V., Maguire, P., Pirmohamed, M., & Turner, R. M. (2020). A Review of the Important Role of CYP2D6 in Pharmacogenomics. Genes, 11(11), 1295. https://doi.org/10.3390/genes11111295

Teleanu, R. I., Niculescu, A. G., Roza, E., Vladâcenco, O., Grumezescu, A. M., & Teleanu, D. M. (2022). Neurotransmitters-Key Factors in Neurological and Neurodegenerative Disorders of the Central Nervous System. International Journal of Molecular Sciences, 23(11), 5954. https://doi.org/10.3390/ijms23115954

Trang, A., & Khandhar, P. B. (2023). Physiology, Acetylcholinesterase. In StatPearls. StatPearls Publishing. https://www.ncbi.nlm.nih.gov/books/NBK539735/

Tunbridge E. M. (2010). The catechol-O-methyltransferase gene: its regulation and polymorphisms. International Review of Neurobiology, 95, 7–27. https://doi.org/10.1016/B978-0-12-381326-8.00002-8

Ventola C. L. (2013). Role of pharmacogenomic biomarkers in predicting and improving drug response: part 1: the clinical significance of pharmacogenetic variants. Pharmacy and Therapeutics, 38(9), 545–560.

Walczak-Nowicka, Ł. J., & Herbet, M. (2021). Acetylcholinesterase Inhibitors in the Treatment of Neurodegenerative Diseases and the Role of Acetylcholinesterase in their Pathogenesis. International Journal of Molecular Sciences, 22(17), 9290. https://doi.org/10.3390/ijms22179290

Wilke, R. A., Lin, D. W., Roden, D. M., Watkins, P. B., Flockhart, D., Zineh, I., Giacomini, K. M., & Krauss, R. M. (2007). Identifying genetic risk factors for serious adverse drug reactions: current progress and challenges. Nature reviews. Drug Discovery, 6(11), 904–916. https://doi.org/10.1038/nrd2423

Wyns, A., Hendrix, J., Lahousse, A., De Bruyne, E., Nijs, J., Godderis, L., & Polli, A. (2023). The Biology of Stress Intolerance in Patients with Chronic Pain-State of the Art and Future Directions. Journal of Clinical Medicine, 12(6), 2245. https://doi.org/10.3390/jcm12062245

Xiang, C., Cong, S., Liang, B., & Cong, S. (2020). Bioinformatic gene analysis for potential therapeutic targets of Huntington's disease in pre-symptomatic and symptomatic stage. Journal of Translational Medicine, 18(1), 388. https://doi.org/10.1186/s12967-020-02549-9

Yam, M. F., Loh, Y. C., Tan, C. S., Khadijah Adam, S., Abdul Manan, N., & Basir, R. (2018). General Pathways of Pain Sensation and the Major Neurotransmitters Involved in Pain Regulation. International Journal of Molecular Sciences, 19(8), 2164. https://doi.org/10.3390/ijms19082164

Yang, S., & Chang, M. C. (2019). Chronic Pain: Structural and Functional Changes in Brain Structures and Associated Negative Affective States. International Journal of Molecular Sciences, 20(13), 3130. https://doi.org/10.3390/ijms20133130

Young, E. E., Lariviere, W. R., & Belfer, I. (2012). Genetic basis of pain variability: recent advances. Journal of Medical Genetics, 49(1), 1–9. https://doi.org/10.1136/jmedgenet-2011-100386

Zhao, F., Cheng, Z., Piao, J., Cui, R., & Li, B. (2022). Dopamine receptors: Is it possible to become a therapeutic target for depression? Frontiers in Pharmacology, 13, 947785. https://doi.org/10.3389/fphar.2022.947785

Zhao, S. J., Zhou, W., Chen, J., Luo, Y. J., & Yin, G. Y. (2018). Bioinformatics analysis of the molecular mechanisms underlying traumatic spinal cord injury. Molecular Medicine Reports, 17(6), 8484–8492. https://doi.org/10.3892/mmr.2018.8918

Zieglgänsberger W. (2019). Substance P and pain chronicity. Cell and Tissue Research, 375(1), 227–241. https://doi.org/10.1007/s00441-018-2922-y

Zięba, A., Matosiuk, D., & Kaczor, A. A. (2023). The role of genetics in the development and pharmacotherapy of depression and its impact on drug discovery. International Journal of Molecular Sciences, 24(3), 2946. https://doi.org/10.3390/ijms24032946

Downloads

Published

2024-06-27

How to Cite

Jani, J., Liew Sat Lin, C., D. Mudin, D. K. and Muniandy, R. K. (2024) “Bridging the genetic gulf: a deep dive into neurotransmission, pharmacogenomics, and genetic variations for optimal pain management”, Neuroscience Research Notes, 7(2), pp. 316.1–316.15. doi: 10.31117/neuroscirn.v7i2.316.