Post-acute sequelae SARS-CoV-2 infection and neuropathic pain: a narrative review of the literature and future directions

May 14, 2025Pain management

Long-term nerve pain after COVID-19 infection: a review and future research ideas

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Abstract

Approximately 10% of people with SARS-CoV-2 may develop chronic neuropathic pain.

Neuropathic pain can occur during acute, post-acute, and long-COVID phases of SARS-CoV-2 infection.
Factors such as disease severity, higher body mass index, prior psychological conditions, and addiction history may be linked to post-acute SARS-CoV-2 neuropathic symptoms.
Sex differences could affect the prevalence of these symptoms.
PASC symptoms may complicate pain perception due to their multisystem nature, including mood disorders and cognitive dysfunction.
Potential underlying mechanisms include immune system changes, ongoing effects of viral proteins, and alterations in brain structure.
Management of neuropathic pain generally involves various treatment strategies.

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PURPOSE OF REVIEW: Neuropathic pain is a recognized and debilitating symptom of SARS-CoV-2 infection across acute, post-acute, and long-COVID phases. Initially emerging as acute or subacute symptoms, these neuropathic manifestations can evolve into chronic conditions, with approximately 10% of all SARS-CoV-2 cases (estimated 65 million individuals globally) developing post-acute SARS-CoV-2 (PASC) neuropathic sequalae. Given the limited literature specifically addressing neuropathic pain related to PASC, a deeper understanding is needed to improve management and reduce patient burden.

RECENT FINDINGS: PASC symptoms are associated with disease severity, elevated body mass indexes, preexisting psychological conditions, and addiction history. Sex differences appear to influence prevalence, and the multisystem nature of PASC complicates symptom presentation, with mood disorders, fatigue, and cognitive dysfunction contributing to altered pain perception. Proposed mechanisms include immune dysregulation, persistent viral protein effects, and neuroanatomical changes. Management typically involves a multimodal approach.

SUMMARY: This review examines SARS-CoV-2 neuropathic pain across the illness trajectory, examining its pathophysiology, prevalence, and treatment. It highlights the potential for subacute neuropathic symptoms to become chronic and calls for future research to refine long-term management strategies and assess broader healthcare implications.

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