Persistent pain after a UTI may be due to an overgrowth of nerve cells

Pain that persists even after a urinary tract infection has supposedly passed seems to be down to an overgrowth of nerve cells in the bladder.

Urinary tract infections (UTIs) are most commonly caused by the bacterium Escherichia coli making its way from faecal matter to the urethra, bladder or kidneys. Common symptoms include pain while urinating and the urge to urinate more often than normal. These infections mainly affect women, of whom around half develop a UTI at some point in their life.

“One of the major issues regarding urinary tract infections is its pretty high rate of recurrence,” says Soman Abraham at Duke University in North Carolina. “But after treatment, some people seem to have the same UTI symptoms even when there’s no longer an infection.”

To understand the root of the ongoing symptoms, Abraham and his colleagues analysed bladder tissue biopsies from eight women who reported continued pelvic pain from recurrent UTIs, despite tests revealing there was no E. coli in their urine. They also collected biopsies from three women who had never knowingly had a UTI. No transgender people were included in the study.

The team found that those with persistent UTI symptoms had abnormal overgrowths of nerve cells in their bladders, compared with the other women. These nerve cells also had higher levels of a peptide called substance p, which causes pain and inflammation.

Next, the team induced recurrent UTIs in mice, which similarly showed signs of lasting pain after their infections had cleared. Taking a closer look at the mice’s bladders, the researchers found that immune cells called mast cells that were located near nerve cells were highly activated. Mast cells produce so-called nerve growth factors, which stimulate nerve cell production.

The antibiotics used to treat UTIs aren’t often selective in the bacteria they target, affecting some beneficial strains around nerve cells. This damages the nerve cells, which causes mast cells to go into overdrive to help replace them, says Abraham.

In the final part of the experiment, the researchers induced a UTI in a different set of mice before treating them with compounds that suppress the production of nerve growth factors. They then induced two further UTIs, finding that the mice showed no signs of lingering pain.

The team hopes the results could help with the development of an effective treatment to prevent ongoing symptoms in people. “We could actually prevent the growth of these nerves and thereby prevent the pain and frequency of urination,” says Abraham.

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