365: Unmasking Acute Neurotoxicity During Pain Management of Lumbar Radiculopathy: A Case Report

Topic: Clinical Science
Subtopic: Pain category (ICD-11), Chronic primary musculoskeletal pain, Pharmacological treatments, Genetics and Epigenetics, Imaging (e.g. fMRI, PET, MRS)

Background and Aims: Chronic lumbar radiculopathy is a common cause of morbidity often requiring multimodal analgesia. However, multi-analgesic therapy involving serotonergic opioids, corticosteroids, and gabapentinoids presents significant neurotoxic risks, particularly in patients with susceptible pharmacogenomic profiles. This case report aims to describe a patient with chronic lumbar radiculopathy who developed acute neurologic deterioration while receiving therapeutic-dose tramadol in combination with pregabalin and dexamethasone. The clinical presentation raised suspicion for altered CYP2D6 activity.

Methods: We report the case of a 37-year-old Asian female with a prior L4-L5 discectomy who presented with acute, severe left-sided lumbar radiculopathy. Escalation to a higher dose (but within therapeutic level) tramadol, pregabalin, and dexamethasone resulted in sudden unresponsiveness with flaccid tone and eyelid fluttering by the third hospital day. The patient recovered after diazepam administration. Neuroimaging and EEG findings were unremarkable. Diagnoses of Functional Neurologic Disorder (FND) precipitated by drug-induced physiological stress and atypical Serotonin Syndrome were favored. Discontinuation of tramadol and pregabalin, followed by transition to morphine sulfate, achieved sustained analgesia without recurrence of neurotoxicity.

Results: Discontinuation of tramadol and pregabalin, followed by transition to morphine sulfate, achieved sustained analgesia without recurrence of neurotoxicity. A plausible explanation is that a CYP2D6 polymorphic variant may have contributed to her exaggerated response to high-dose tramadol, while the safe transition to morphine, a CYP2D6-independent opioid, supports altered tramadol metabolism as a potential factor in her atypical neurotoxic presentation.

Conclusions: This case highlights the importance of recognizing pharmacogenetic vulnerability, particularly CYP2D6 polymorphisms. The combination of poor analgesic response and disproportionate adverse neurologic effects prompts reconsideration of tramadol use rather than dose escalation. For patients with suspected CYP2D6 polymorphisms and refractory pain, opioid rotation to CYP2D6-independent agents, such as morphine, may provide effective analgesia with a lower risk of recurrent toxicity.

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Presenting Author: Jo Mari Darvin C. Adorador, MD, DPBA
Submitting Author: Jo Mari Darvin Adorador

Senior Author: Dr. Lyde M. Alday-Magpantay, MD, MSc, DPBPM

IASP 2026 Global Year theme of Neuropathic Pain: Yes