Shingles can cause severe chronic pain – new research on how exosomes alter neurons offers pathways to treatment
Varicella zoster virus, also known as human herpesvirus 3, causes chickenpox and shingles. BSIP/Universal Images Group via Getty Images Shingles can cause pain that is notoriously difficult to manage and can last for months to years for some people.
Shingles is a painful skin rash caused by the reactivation of the varicella zoster virus, the same virus responsible for chickenpox. This virus infects over 90% of the world’s population, often during childhood in temperate regions or later in life in tropical areas. After the initial chickenpox infection, the virus remains dormant in pain-sensing neurons (nerve cells that detect pain signals) for decades. In about a third of people, the virus reactivates later in life, causing shingles. While the rash typically heals within weeks, about 10% to 18% of patients develop post-herpetic neuralgia (PHN), a severe chronic pain condition that can last months to years. PHN is more common in older adults, with the risk increasing significantly with age.
Post-herpetic neuralgia (PHN) is notoriously difficult to treat, with less than 50% of patients achieving meaningful pain relief. The pain can be so severe that it leads to a significant decline in quality of life and may even contribute to emotional distress or suicidal thoughts. Despite its debilitating effects, the underlying mechanisms driving PHN are not fully understood, which limits treatment options. Current therapies focus on symptom relief rather than addressing the root cause. Research suggests that the condition may involve ongoing damage to sensory nerve fibers (nerve cells in the skin that detect touch and pain), but why these fibers fail to repair after the virus reactivates remains unclear.
Exosomes are tiny sacs released by cells that carry proteins and genetic material, acting as messengers between cells. They play a key role in normal bodily functions but may also contribute to disease. In new research published in Annals of Neurology, scientists investigated whether exosomes in the blood of PHN patients could explain the condition’s puzzling features. The team isolated exosomes from the blood of seven PHN patients and seven people without PHN. They found that exosomes from PHN patients contained higher levels of proteins that suppress neuron growth. When these exosomes were exposed to human sensory neurons in a lab, the neurons were unable to grow or form strong networks, suggesting these exosomes may prevent nerve repair.
The study revealed that exosomes from PHN patients cause pain-sensing neurons to become overactive and hypersensitive to pain signals. These exosomes also prevented neurons from forming *growth cones* (structures needed for nerve repair). This suggests that exosomes may contribute to the chronic pain and failed nerve regeneration seen in PHN. The findings imply that targeting exosomes or their cargo could lead to new treatments for PHN and possibly other painful nerve conditions, such as *diabetic neuropathy* (nerve damage caused by diabetes). The research team is now collecting blood samples from shingles patients over a year to identify specific exosome components linked to PHN.
