Dataset Information

Immunomodulation-A Molecular Solution to Treating Patients with Severe Bladder Pain Syndrome?

ABSTRACT:

Background

Patients with bladder pain syndrome experience debilitating pain and extreme frequency of urination. Numerous therapeutic approaches have been tested, but as the molecular basis of disease has remained unclear, specific therapies are not available.

Objective

Recently, a systematic gene deletion strategy identified interleukin-1 (IL-1) hyperactivation as a cause of severe cystitis in a murine model. Treatment with an IL-1 receptor antagonist (IL-1RA) restored health in genetically susceptible mice, linking IL-1-dependent inflammation to pain and pathology in the bladder mucosa. The study objective was to investigate whether IL-1RA treatment might be beneficial in patients with bladder pain syndrome.

Design setting and participants

Patients diagnosed with bladder pain syndrome were invited to participate and subjected to daily IL-1RA injections for 1 wk, followed by a treatment break. Patients with other urological disorders accompanied by pain were included as controls.

Outcome measurements and statistical analysis

When symptoms returned, treatment was resumed and responding patients were maintained on treatment long term, with individualized dosing regimens. Symptom scores were recorded and molecular effects were quantified by neuropeptide and gene expression analysis. DNA samples were subjected to exome genotyping.

Results and limitations

IL-1RA treatment reduced bladder pain and the frequency of urination in 13/17 patients (p < 0.001). Substance P levels in urine were lowered, and responders returned to a more normal lifestyle. Neuroinflammatory-dependent and IL-1-dependent gene networks were inhibited, as well as regulators of innate immunity. Genotyping revealed disease-associated IL1R1, NLRP3, and IL1RN DNA sequence variants in the responders. Controls did not benefit from IL-1RA treatment, except for one patent with cystitis cystica.

Conclusions

In this clinical study, IL-1RA treatment is proposed to reduce chronic bladder pain, immediately and in the long term. Despite the limited number of study patients, the potent acute effect and lasting symptom relief indicate that this therapeutic approach may be worth exploring in controlled clinical trials.

Patient summary

Treatment with an interleukin-1 (IL-1) receptor antagonist is proposed for treating bladder pain syndrome, as it can result in symptom relief and increase quality of life. Reduced neuroinflammation and IL-1 signaling provided molecular evidence of the treatment effects.

SUBMITTER: Wullt B

PROVIDER: S-EPMC8385293 | biostudies-literature |

REPOSITORIES: biostudies-literature

ACCESS DATA

Similar Datasets

Project description:ObjectiveTo compare bladder sensitivity between patients with pelvic pain and patients who were pain free, undergoing noninvasive, controlled bladder distension via diuresis. We also sought to measure potential mechanisms underlying bladder sensitivity.DesignProspective observational study.SettingCommunity teaching hospital.PopulationReproductive-age women with non-bladder chronic pelvic pain (CPP, n = 23), painful bladder syndrome (PBS, n = 23), and pelvic pain-free controls (n = 42) METHODS: Participants were compared on cystometric capacity, pelvic floor pressure-pain thresholds (PPTs), pelvic muscle function, O'Leary-Sant bladder questionnaire, and psychosocial instruments using Wilcoxon rank-sum tests. Multivariate regression was used to identify factors underlying bladder pain phenotypes.Main outcome measuresPelvic floor pain thresholds; self-reported bladder distension pain.ResultsParticipants with PBS exhibited higher bladder distension pain than those with CPP, with both groups reporting higher pain levels than controls (P < 0.05). No significant associations were found between bladder distension pain and pelvic muscle structure or pain sensitivity measures; however, bladder distension pain positively correlates with both vaginal PPTs adjacent to the bladder (r = 0.46) and pain with transvaginal bladder palpation (r = 0.56). Pain at maximal distension was less influenced by somatic sensitivity than bladder symptoms (r = 0.35 versus r = 0.59; P < 0.05). Multivariate regression identified three independent components of bladder symptoms in PBS: bladder distension pain, bladder sensation, and somatic symptoms.ConclusionsDiuresis-induced bladder pain differentiates CPP from PBS. Experimental bladder pain is not predicted by pelvic floor sensitivity. Compared with patient-reported outcomes it appears less influenced by psychological factors. Further study is needed to determine whether screening for experimental bladder pain sensitivity could predict future risk of PBS.Tweetable abstractControlled, water ingestion-provoked bladder pain can objectively identify visceral pain sensitivity.