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PubMed This is a summary of 23 peer-reviewed journal articles Updated
Neurology

How Infections Damage Nerves: The Biological Path to Pain

At a Glance

Post-infectious neuralgia can persist because an infection may injure nerve fibers, cause inflammation, or change how pain signals are processed. Postherpetic neuralgia has the strongest evidence for these changes, while mechanisms after treated Lyme disease and in Long COVID remain uncertain.

When an infection clears but the pain remains, it is often because the pathogen has left behind a changed nervous system. The transition from an active infection to a chronic pain state involves a series of biological mechanisms. Understanding these models helps explain why the pain feels so intense. It is important to note that human evidence is strongest for injury and inflammation in established Postherpetic Neuralgia (PHN), while mechanisms of post-treatment Lyme symptoms and Long COVID neuropathic symptoms remain uncertain.

How Different Pathogens Target Nerves

While many infections can be associated with pain, they do so through different pathways:

  • Varicella-Zoster Virus (VZV/Shingles): VZV specifically seeks out nerve tissue. It lives dormant in your sensory ganglia—the hubs where nerve cell bodies reside [1]. When it reactivates, it travels down the nerve fibers, causing injury and inflammation [2]. This can lead to a loss of the small nerve fibers in your skin, leaving the remaining nerves prone to misfiring [3].
  • Lyme Disease (Bannwarth Syndrome): In active Lyme neuroborreliosis, the bacteria (Borrelia burgdorferi) can cause inflammation of the nerve roots (radiculoneuritis) [4]. For post-treatment Lyme disease syndrome, where symptoms persist after adequate antibiotics, the mechanisms are unconfirmed, but researchers have proposed ongoing immune responses rather than persistent infection requiring prolonged antibiotics [5][6].
  • HIV: HIV-associated neuropathy is widely documented. The virus itself may produce proteins toxic to nerve cells [7]. Additionally, some older antiretroviral medications caused mitochondrial toxicity, leading to a progressive breakdown of nerve fibers [8][9].
  • COVID-19: Emerging hypotheses suggest that neuropathic pain in “Long COVID” may stem from immune-mediated injury or vascular changes [10]. Proposed mechanisms include a “cytokine storm” altering pain fibers, or microvascular injury affecting oxygen delivery to nerves, though these are not confirmed explanations for an individual patient [11][12].

Peripheral Sensitization: The “Leaky” Nerve

One proposed model for chronic pain involves changes in the peripheral nervous system. When a nerve is injured, it may undergo ion-channel remodeling [13].

Nerves use tiny gates called ion channels to send electrical signals. After an injury, these gates may become dysfunctional. This can create an ectopic pacemaker—a spot on the nerve that fires off pain signals spontaneously [14][15]. This is why you might feel burning or “electric shocks” while sitting perfectly still.

Central Sensitization: A Proposed Model

If the peripheral nerves continue to bombard the spinal cord with pain signals, researchers propose that the central nervous system may adapt. This is called central sensitization, often described as the “volume knob” of the nervous system being turned up [16][17].

Features of this model include:

  1. Wind-up: The spinal cord becomes hyper-responsive, turning a mild signal into a severe pain response [14].
  2. Loss of Inhibition: The brain’s signals that normally “dampen” pain (using neurotransmitters like GABA) may become less effective [18][19].
  3. Glial Activation: Supportive cells called microglia and astrocytes may release inflammatory chemicals that keep neurons on high alert [20][21].

These mechanisms are useful models for understanding pain, but they do not diagnose an individual patient, nor can a routine blood or spinal-fluid test measure your “volume knob.” Additional testing is considered when symptoms are atypical, spreading, or accompanied by weakness [22][23].

Common questions in this guide

Why can nerve pain continue after an infection is gone?
An infection may injure nerve fibers or leave inflammation and altered pain signaling behind, so pain can continue after the pathogen is no longer active. The evidence is strongest for nerve injury and inflammation in postherpetic neuralgia, the pain that can follow shingles; the causes of persistent symptoms after treated Lyme disease or in Long COVID remain uncertain.
What causes burning or electric-shock sensations when I am not moving?
An injured nerve can develop changes in its electrical channels and fire pain signals without a normal trigger. This peripheral sensitization model can help explain burning or electric-shock sensations at rest, but it does not by itself confirm a diagnosis.
Is central sensitization a confirmed diagnosis that a blood test can detect?
Central sensitization is a proposed model in which the spinal cord and brain become more responsive to pain signals. There is no routine blood or spinal-fluid test that measures it directly, so clinicians use the symptom pattern and may order other tests when symptoms are unusual, spreading, or accompanied by weakness.
Does ongoing pain after Lyme treatment mean the infection is still active?
Not necessarily. Persistent symptoms after adequate Lyme treatment have unconfirmed causes and may involve ongoing immune responses rather than bacteria that require prolonged antibiotics; a clinician should assess for active infection and other neurologic conditions.
Which infections are linked to post-infectious nerve pain?
Varicella-zoster virus, which causes shingles, Lyme neuroborreliosis, HIV, and COVID-19 are discussed as infections that can be associated with nerve pain through different mechanisms. The strength of evidence differs: established postherpetic neuralgia has stronger evidence for nerve injury and inflammation, while mechanisms in post-treatment Lyme symptoms and Long COVID remain uncertain.
When should persistent nerve pain lead to more testing?
Further evaluation may be appropriate when pain is atypical, spreading, accompanied by weakness, or associated with signs of active infection or another neurologic problem. The specific tests depend on the symptoms and examination; no single routine test measures the nervous system's pain volume knob.

Questions to Ask Your Doctor

Curated prompts to bring to your next appointment.

  1. 1.Based on my history, do you think my pain is driven more by structural nerve damage or by functional 'misfiring' (sensitization)?
  2. 2.For my specific case, does the evidence suggest the infection caused direct damage to the nerve hubs, or was the damage primarily from an immune response?
  3. 3.Does the fact that my pain is localized help determine if central sensitization is a major factor in my symptoms?
  4. 4.Are there specific tests indicated to rule out other neurologic disorders or active infection?
  5. 5.If my nerves have undergone 'ion-channel remodeling,' what types of medications are designed to stabilize those electrical gates?

Questions For You

Tap a prompt to share your answer — we'll use it plus this page's context to start a tailored conversation.

References

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This page explains how infections may injure nerves and how pain-sensitization models are used for education only; it does not provide medical advice. A healthcare professional should evaluate persistent, spreading, or weakness-associated pain.

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