Recurrent infections drive persistent bladder dysfunction and pain via sensory nerve sprouting and mast cell activity,2024, BYRON W. HAYES et al

Abstract
Urinary tract infections (UTIs) account for almost 25% of infections in women. Many are recurrent (rUTI), with patients frequently experiencing chronic pelvic pain and urinary frequency despite clearance of bacteriuria after antibiotics.

To elucidate the basis for these bacteria-independent bladder symptoms, we examined the bladders of patients with rUTI. We noticed a notable increase in neuropeptide content in the lamina propria and indications of enhanced nociceptive activity. In mice subjected to rUTI, we observed sensory nerve sprouting that was associated with nerve growth factor (NGF) produced by recruited monocytes and tissue-resident mast cells. Treatment of rUTI mice with an NGF-neutralizing antibody prevented sprouting and alleviated pelvic sensitivity, whereas instillation of native NGF into naïve mice bladders mimicked nerve sprouting and pain behavior.

Nerve activation, pain, and urinary frequency were each linked to the presence of proximal mast cells, because mast cell deficiency or treatment with antagonists against receptors of several direct or indirect mast cell products was each effective therapeutically.

Thus, our findings suggest that NGF-driven sensory sprouting in the bladder coupled with chronic mast cell activation represents an underlying mechanism driving bacteria-independent pain and voiding defects experienced by patients with rUTI.

https://www.science.org/doi/10.1126/sciimmunol.adi5578

 

I recently read about a similar discovery about lower back pain: compressing the discs releases a factor that encourages nerve growth into the disc.

 

I find this fascinating. I have painful bladder syndrome and widespread body pain/constant migraines in addition to my ME and PoTS. I’ve often been told there’s a role to play with the mast cells interacting with the small fibre nerves.

My peripheral nerves on skin biopsy had signs of “sprouting” and were spontaneously active/partially depolarised on microneurography. Although I appreciate these are research based techniques which might be questionable.

Like most of us my neurological symptoms have always significantly worsened post infection and so I feel there must be some immune-neural pathway being affected.

If only they could figure it out I’d get some relief to my sensory symptoms which are pure hell and not controlled by any medication to date.