By Dr. Fabiano de Abreu Agrela Rodrigues, Bioinformatician and Neuroscientist specializing in Functional Genomics.
Lumbar disc herniation remains a leading cause of back pain and sciatica in adults, affecting millions worldwide and frequently leading to significant limitations in mobility and quality of life. While mechanical wear, aging, sedentary lifestyle, and repetitive trauma are well-known factors, recent genetic research highlights an important hereditary component in this condition. Genes involved in connective tissue structure, such as COL11A1, which encodes the alpha-1 chain of type XI collagen, play a crucial role in maintaining the integrity of the extracellular matrix of intervertebral discs. Specific variants in this gene, such as rs1676486, have been associated in studies with Chinese, Japanese, and other populations with an increased risk of disc degeneration and lumbar herniation. For example, the T allele of this variant can reduce mRNA stability and protein expression, resulting in more fragile discs prone to protrusion or rupture, which interacts with environmental factors to amplify the degenerative process and the muscle defense mechanism known as “locking” or protective spasm.
From a neuroscientific point of view, pain perception in this condition depends not only on mechanical nerve compression but also on molecular mechanisms that modulate nociceptive transmission in the peripheral nervous system. The SCN9A gene, responsible for encoding the voltage-gated sodium channel Nav1.7 expressed in sensory neurons, is particularly relevant. Variants such as rs6746030 have been linked to greater pain intensity in patients with symptomatic disc herniation, including chronic lumbosciatica. The minor A allele of this variant appears to increase channel activity, leading to greater neuronal excitability and, consequently, an amplification of pain perception in response to stimuli such as inflammation or nerve root compression. Studies in cohorts of patients with herniated discs, osteoarthritis, and other painful conditions confirm that carriers of this variant report higher pain scores, illustrating how subtle genetic variations can transform a structural injury into a more intense and persistent painful experience.
In the field of pharmacogenetics, which investigates how the individual genome influences the response to medications, the CYP2C9 gene emerges as a central element in the metabolism of common nonsteroidal anti-inflammatory drugs (NSAIDs), such as ibuprofen, celecoxib, and others. Variants such as 2 (rs1799853) and 3 (rs1057910) reduce hepatic enzyme activity to varying degrees, classifying individuals as intermediate or poor metabolizers. In these cases, the drug accumulates in the plasma, prolonging its half-life and increasing the risk of adverse effects, including gastrointestinal toxicity such as mucosal irritation, ulcers, or bleeding, which can be especially problematic in people with a history of stomach problems, such as gastroparesis. Guidelines from the Clinical Pharmacogenetics Implementation Consortium (CPIC), updated based on robust evidence, recommend dose adjustments or preference for alternatives in reduced metabolizers to minimize these risks.
The integration of this knowledge highlights the potential of personalized medicine: genetic testing can identify predispositions to disc degeneration, hypersensitivity to pain, and altered responses to analgesics, allowing for more precise management approaches. However, this genetic data is only one piece of the puzzle, which must be interpreted within the complete clinical context, including imaging studies, current symptoms, and comorbidities. Science is advancing to make the treatment of lower back pain more individualized, but the essential step remains the same: consulting qualified healthcare professionals, such as physicians, orthopedists, neurologists, or geneticists, who can integrate this scientific information into safe and effective therapeutic decisions.
This text summarizes general concepts extracted from publicly available scientific literature and does not constitute medical advice, diagnosis, or treatment recommendation. Any questions related to personal health should be discussed exclusively with a qualified professional, who will assess the case individually.
Dr. Fabiano de Abreu Agrela Rodrigues MRSB holds a post-PhD in Neuroscience and is an elected member of Sigma Xi – The Scientific Research Honor Society (more than 200 members of Sigma Xi have received the Nobel Prize), as well as being a member of the Society for Neuroscience in the United States, the Royal Society of Biology and The Royal Society of Medicine in the United Kingdom, the European Society of Human Genetics in Vienna, Austria, and the APA – American Philosophical Association in the United States. He holds a Master’s degree in Psychology and a Bachelor’s degree in History and Biology. He is also a Technologist in Anthropology and Philosophy, with several national and international degrees in Neuroscience and Neuropsychology. Dr. Fabiano is a member of prestigious high IQ societies, including Mensa International, Intertel, ISPE High IQ Society, Triple Nine Society, ISI-Society, and HELLIQ Society High IQ. He is the author of more than 300 scientific studies and 30 books. He is currently a visiting professor at PUCRS in Brazil, UNIFRANZ in Bolivia and Santander in Mexico. He also serves as Director of CPAH – Centro de Pesquisa e Análises Heráclito and is the creator of the GIP project, which estimates IQ through the analysis of genetic intelligence. Dr. Fabiano is also a registered journalist, having his name included in the book of records for achieving four records, one of which is for being the greatest creator of characters in the history of the press.