Peptidergic bladder afferent nerves implicated in interstitial cystitis pain

Key Points

Atlanta-Neurotrophic factors that appear in interstitial cystitis/bladder pain syndrome (IC/BPS) patients' urine and disappear with onabotulinumtoxinA (Botox) treatment point to peptidergic primary bladder afferent nerves as the root of patients' pain and other symptoms.

What's more, the study presented at the AUA annual meeting in Atlanta confirms a trend in onabotulinumtoxinA treatment of IC/BPS symptoms-injection only in the trigone, the area of the bladder with the most pain-sensing afferent nerves.

The two neurotrophic factors tested by first author Rui Pinto, MD, and colleagues at Hospital de São João in Porto, Portugal, were brain-derived neurotrophic factor (BDNF) and glial cell line-derived neurotrophic factor (GDNF). Both are important in maintaining and supporting bladder sensory nerves, but they are associated with different receptors and respond to distinct neurotrophic factors. BDNF is upregulated and synthesized in response to peripheral inflammation. Increases in nerve growth factor (NGF) are associated with increased expression of BDNF in peptidergic sensory afferents, which are the most common primary bladder afferents, and increases in NGF are also associated with the heightened pain sensitivity associated with neuropathic pain. GDNF is mostly associated with nonpeptidergic C fibers in afferent nerves that primarily innervate the distal urethra.

The investigators followed patients at 1, 3, and 6 months after treatment, evaluating pain scores on a visual analog scale, a 3-day voiding diary for frequency and nocturia, O'Leary-Sant IC Symptom and Problem Index scores, and International Prostate Symptom Score quality of life scores.

Before treatment, normalized levels of NGF and BDNF were both significantly higher in the IC/BPS patients than in controls, but GDNF didn't show any significant differences, noted co-author Tiago Lopes, MD.

One month after treatment, said Dr. Lopes, "We found a significant decrease in NGF and BDNF creatinine ratios and also GDNF creatinine ratio. After 3 months, the values started to increase. At 6 months, the values were more or less like they were at baseline."

What's more, he said, the change in NGF and BDNF levels tracked the change in pain scores, but there was no such correlation for GDNF.

"These data suggest," he concluded, "that neurotrophins are key elements in the pathogenesis of IC/BPS with potential clinical implications."