Guest Editorial: Neurogenetics and the Future of Pain: Reclaiming Reward, Function, and Identity

• pain
• reward deficiency syndrome
• mental health

As pain medicine evolves from a reactive discipline toward one rooted in restoration, personalization, and meaning making, the neurogenetic framework of Reward Deficiency Syndrome (RDS) offers a vital lens to re-examine how we define, measure, and treat chronic pain and its profound effects on mental health and identity.

I am honored to contribute to this special issue of the International Journal of Spine Surgery, curated by Dr. Morgan Lorio, whose editorial insightfully challenges us to think beyond the visible lesion and to explore the neurobiological, psychological, and existential architecture of pain.

Over decades, research from my colleagues and I has illuminated that chronic pain is not simply a matter of nociception or structural compression. Rather, for many individuals, it reflects a neurochemical dysregulation of reward systems—a disrupted glutamatergic-dopaminergic tone that makes it difficult not only to feel relief, but to perceive hope, motivation, and resilience. This understanding of pain intersects addiction science, neurogenetics, epigenetics, and even trauma-informed care, demanding a radical integration of neuroscience with compassionate, person-centered spine care.

When a patient suffers from both pain and compulsive behaviors, or when surgical success does not correlate with emotional relief, we are often witnessing the footprints of RDS. In these moments, our tools must extend beyond the scalpel or fluoroscope. They must include genetically informed diagnostics, dopamine-restorative interventions, and a new language of healing that embraces both structure and soul. Understandably, physicians and surgeons dealing with both acute and chronic pain must become familiar with many people who may present with genetically induced hypodopaminergia and, as such, have a profoundly enhanced sensitivity to pain.

This understanding is no longer just theoretical: it is beginning to shape clinical and even legal outcomes. In July 2025, in a landmark trial in Bexar County, Texas (State of Texas v. [Defendant], 399 District Court, before Judge Frank Castro), genetic evidence of RDS, measured through the Genetic Addiction Risk Score, was successfully introduced during the guilt-innocence phase of a criminal proceeding—a first in US legal history.1 The defendant, a 47-year-old female counselor charged with intoxication manslaughter and intoxication assault, was found to have a Genetic Addiction Risk Score of 10, indicating a significant burden of dopamine-related polymorphisms. The jury, presented with this evidence alongside expert testimony on her dopamine dysregulation and the effects of her prescribed dopamine-modulating medication, acquitted her of all intoxication-related charges. This extraordinary case demonstrates how deeply genetic predisposition and neurochemical dysregulation can influence behavior, perception, and culpability, extending the implications of RDS far beyond the clinic.

For the spine surgeon or pain physician, the lesson is clear: the biology of reward is inseparable from how our patients experience and express pain, make decisions, and respond to treatment. To ignore this dimension risks misunderstanding not only the patient’s suffering but also their humanity.

Increasing evidence suggests that many patients living with chronic pain and maladaptive coping behaviors are not simply lacking willpower or compliance but are struggling under the weight of an inherited hypodopaminergic trait. Such a trait can blunt their capacity to derive motivation and pleasure from activities that should promote healing—be it physical therapy, medication adherence, or even the hope of surgical benefit. Recognizing this reality can guide us to more appropriate interventions, such as pro-dopamine regulatory approaches, psychosocial support attuned to their neurobiology, and realistic goal-setting that honors both their vulnerabilities and their potential (see also the article by Lewandrowski et al).2

Of course, as we move toward integrating neurogenetics into care, we must also engage the ethical, legal, and policy questions it raises. How do we protect patients’ privacy and autonomy while utilizing their genetic information? How can we avoid stigmatizing individuals based on their risk profiles while ensuring they receive appropriate care? Protections under the Genetic Information Nondiscrimination Act3 provide some safeguards in health insurance and employment contexts, but gaps remain that must be addressed. The Bexar County case is a reminder that these questions are not abstract but urgent—and our answers must be informed by science, compassion, and justice.

This special issue, and this moment in our field, offers us a chance to listen more deeply to what pain teaches—not only about the body, but about the brain, and ultimately, about being human. Pain exposes not just where it hurts but who we are: fragile yet resilient beings whose biology and biography intertwine.

I am deeply grateful to Dr. Lorio and the IJSS editorial team for creating this space to explore these questions. To Dr. Kai-Uwe Lewandrowski, whose work in both endoscopic innovation and structural reform continues to lead the field with clarity and vision, I look forward to a shared future of precision pain care that honors both science and suffering.

As we reclaim reward, function, and identity for our patients, may we also reclaim the art of listening—not only to their pain but to the deeper story their biology is telling.

• This manuscript is generously published free of charge by ISASS, the International Society for the Advancement of Spine Surgery. Copyright © 2025 ISASS. To see more or order reprints or permissions, see http://ijssurgery.com.