How medicine is learning to diagnose the undiagnosable through neuroscience, clinical methods, and empathetic approaches
When Ed Mowery described his chronic pain, he didn't just reference a number on a pain scale. "Just imagine the worst burn you've ever had, all over your body, never going away," he said. "I would wake up in the middle of night, screaming at the top of my lungs." Despite approximately 30 major surgeries, spinal cord stimulators, and up to 17 daily medications, his agony persisted 2 . His story illustrates a crucial medical frontier: suffering extends far beyond physical symptoms, dwelling in the complex intersection of biology, psychology, and personal meaning.
The challenge of diagnosing suffering represents one of medicine's most elusive puzzles. Unlike most medical conditions that can be detected through lab tests or imaging, suffering hides in the subjective experience of the person, influenced by fear, meaning, and concerns about the future 1 . As one researcher notes, suffering "involves some symptom or process that threatens the patient because of fear, the meaning of the symptom, and concerns about the future" 1 . Even when two patients present with identical physical symptoms, their suffering may be completely different based on personal interpretations and significance 1 .
In this article, we'll explore how medicine is learning to diagnose the undiagnosable—from groundbreaking neurological interventions to simple questions that can reveal hidden anguish. The relief of suffering depends on physicians acquiring these skills, requiring methods of "empathetic attentiveness and nondiscursive thinking that can be learned and taught" 1 .
Suffering is proposed to be defined as "an unpleasant or even anguishing experience, severely affecting a person at a psychophysical and existential level" 8 . This definition captures suffering's core characteristic: it transcends simple categories of physical or mental distress, instead spanning both realms simultaneously while touching on fundamental questions of meaning and existence.
The distinction between pain and suffering is crucial to understand. Pain can be a source of suffering, but it is not the only one 8 . Social problems like poverty and exclusion, existential problems like grief and stress, and various non-painful conditions can all cause profound suffering 8 . This distinction explains why two patients with identical pain conditions may experience vastly different levels of suffering.
Suffering is fundamentally personal and contextual. The same symptom or condition will produce different levels of suffering in different people based on their personal history, beliefs, values, and social context 1 6 . This is why, as one analyst argues, "human suffering is not defined by abstract categories" and "does not exist independently of humans who are suffering" 6 .
A high-profile example illustrates this point. Robert, a patient experiencing what might be classified as Body Dysmorphic Disorder, spent hours staring in mirrors where his face would "disintegrate" into an assortment of unconnected features 6 . Standard diagnostic criteria captured his symptoms but missed their meaning until exploration revealed a humiliating childhood event that shaped his suffering 6 . This case demonstrates how suffering is rooted in personal history rather than existing as an abstract category.
Modern medicine is engineered to prioritize objective, measurable data. Yet suffering resists this quantification, being inherently subjective 1 6 . As one physician notes, "The complex techniques and methods that physicians usually use to make a diagnosis, however, are aimed at the body rather than the person. The diagnosis of suffering is therefore often missed, even in severe illness and even when it stares physicians in the face" 1 .
This preference for objective findings creates a fundamental tension in diagnosing suffering. The information required is necessarily subjective, which "may pose difficulties for physicians, who tend to value objective findings more highly and see a conflict between the two kinds of information" 1 .
In palliative and serious illness contexts, clinicians encounter what's termed "existential suffering" or "demoralization syndrome" 5 . This is defined as "an incapacitating state of despair resulting from an inner realization that life is futile and without meaning" 5 . This form of suffering manifests through four existential domains:
"Existential suffering affects approximately 13-18% of patients with progressive illness and can correlate with suicidal ideation and exacerbated physical symptoms" 5 . Importantly, it's not identical to clinical depression, which typically involves loss of interest or pleasure in the present moment, whereas existential suffering involves loss of hope, meaning, and anticipatory pleasure 5 .
Researchers have developed various instruments to assess suffering, particularly in palliative and end-of-life contexts. A systematic review protocol registered in 2018 aimed to identify and evaluate measures assessing suffering in patients with advanced disease 3 . The growing number of these instruments reflects increasing recognition that "suffering assessment is, by definition, subjective, and influenced by physical, psychological, social and spiritual factors that interact with each other" 3 .
Perhaps surprisingly, one of the most effective tools for diagnosing suffering is remarkably simple: asking "Are you at peace?" 5 . A "no" answer should prompt further exploration with follow-up questions such as "What's keeping you from being at peace?" or "What worries you the most about your illness?" 5 . This straightforward approach bypasses complex assessment tools and directly addresses the patient's subjective experience.
| Assessment Method | Key Features | Clinical Context |
|---|---|---|
| Direct Question | Simple questioning: "Are you at peace?" 5 | Quick screening in time-limited settings |
| Validated Instruments | Multi-dimensional scales evaluating physical, psychological, social, spiritual domains 3 | Research and comprehensive palliative care assessment |
| Existential 'Cue' Listening | Attending to patient expressions of meaninglessness, isolation, or faith crises 5 | Routine clinical encounters with seriously ill patients |
| Narrative Exploration | Exploring personal history and meaning of symptoms 6 | Psychological therapy and complex cases |
Notably, no associations have been found between existential suffering and time since diagnosis, stage of disease, or type of treatment 5 , highlighting that suffering depends more on personal meaning and resources than medical characteristics alone.
While suffering extends beyond physical pain, chronic pain remains a significant source of suffering for an estimated 50 million adults in the United States 2 7 . For those like Ed Mowery, standard treatments fail, leading researchers to explore innovative approaches to alleviate both the pain and the suffering it causes.
Dr. Prasad Shirvalkar, a neurologist at University of California San Francisco, led a groundbreaking trial exploring whether personalized deep brain stimulation could interrupt chronic pain signals. "I think of chronic pain as a fire alarm," Shirvalkar explains. "The alarm is helpful for acute pain. We want to be able to know when there's an emergency. In chronic pain, it's as if the fire alarm is going off, but we can't identify the fire" 7 .
The study employed an intensive, rigorous approach with six patients suffering from various types of longstanding chronic pain unrelieved by other treatments 2 . The experimental procedure involved several sophisticated stages:
Researchers implanted electrodes to read signals from and stimulate 14 different brain locations, recognizing that pain involves multiple interconnected brain areas rather than a single "pain center" 2 .
Over ten days, researchers tested various combinations to decipher pain biomarkers—distinctive neural patterns corresponding to individual patients' high-pain states 2 .
Using artificial intelligence, the team developed personalized algorithms that delivered bursts of stimulation specifically when pain signals surged 2 .
Patients were followed for an average of 22 months, including a phase where they randomly received either active stimulation or inactive sham stimulation without knowing which 2 .
| Outcome Measure | Personalized Stimulation | Sham Stimulation |
|---|---|---|
| Average Daily Pain Reduction | ~60% reduction 2 | Almost no benefit 2 |
| Medication Use | Two patients stopped all opioids; two drastically reduced use 2 | No significant reduction |
| Functional Improvement | Improved walking, mood, daily activities, sleep, and enjoyment of life 2 | No significant improvement |
| Stimulation Time | 7-55% of the time (response-triggered) 2 | N/A |
The results offered promising evidence for personalized neuromodulation. The approach functioned like "a thermostat for pain" 2 , delivering stimulation only when needed rather than continuously. This potentially avoids a pitfall of conventional stimulation where "the brain might adapt and learn to ignore it" 2 .
The study also provided broader insights into pain mechanisms. As Dr. Edward Chang, senior author of the study, noted, "We're building these computational models of how those parts of the brain work. We look across people who have different conditions and we look at when people have the symptoms and when they don't" 2 . This modeling advances both treatment and fundamental understanding of pain and suffering.
| Tool/Method | Function/Application | Example Use |
|---|---|---|
| Deep Brain Stimulation (DBS) | Delivers electrical impulses to specific brain regions to modulate neural activity 2 | Disrupting pain signals in chronic pain conditions 2 7 |
| Psychometric Instruments | Validated questionnaires and scales to quantify subjective experiences of suffering 3 | Systematically assessing suffering dimensions in research and clinical care 3 |
| Genetic Analysis | Identifies genetic variants associated with pain sensitivity and chronic pain conditions 4 | Discovering SLC45A4 gene variant linked to higher pain reporting 4 |
| Cryo-Electron Microscopy | Determines 3D structure of proteins and molecular complexes at atomic resolution 4 | Visualizing structure of SLC45A4 transporter protein 4 |
| Psychedelic-Assisted Therapy | Uses psychedelic compounds to facilitate therapeutic psychological experiences 9 | Investigating RE104 (psilocybin derivative) for adjustment disorder to serious diagnosis 9 |
Beyond specific tools or questions, diagnosing suffering requires a fundamental shift in clinical approach. As one perspective argues, "Knowing patients as individual persons well enough to understand the origin of their suffering and ultimately its best treatment requires methods of empathic attentiveness and nondiscursive thinking that can be learned and taught" 1 .
This approach recognizes that "suffering cannot be treated unless it is recognized and diagnosed" 1 , and that diagnosis depends on seeing the person beyond their physical symptoms. Concerns about the discomfort of listening to patients' severe distress are "usually more than offset by the gratification that follows the intervention" 1 .
Effective diagnosis of suffering typically requires moving beyond medical silos. As existential suffering demonstrates, collaborating with "social workers, chaplains, or psychologists is vital to better understand a patient's suffering" 5 . Each discipline brings distinct perspectives and tools for assessing different dimensions of suffering.
This integrated approach aligns with understanding persons as "psychophysical, socioculturally situated beings" 8 whose suffering has bodily, psychological, and sociocultural dimensions simultaneously. The clinical assessment must therefore extend beyond biological factors to include "the person's attitude, resources for their management, as well as choices and commitments related to that person's attachment to life and the world" 8 .
The growing ability to diagnose suffering represents a significant evolution in medicine's approach to human distress. From simple questions like "Are you at peace?" to sophisticated neural biomarkers and brain stimulation technologies, clinicians and researchers are developing multifaceted approaches to identify and address this most human of experiences.
What emerges clearly across these diverse approaches is that suffering, while subjective, is indeed diagnosable through appropriate methods. It requires listening to personal narratives, understanding individual histories, and recognizing the unique meanings that patients attach to their symptoms and experiences.
As research continues to refine our understanding of suffering's mechanisms and manifestations, the fundamental requirement remains human connection: the empathic attentiveness that allows one person to recognize and respond to suffering in another. In the words of one medical perspective, "Often, questioning and attentive listening, which take little time, are in themselves ameliorative" 1 —offering both diagnosis and the beginning of relief through the simple act of being heard and understood.