The pathophysiology of interstitial cystitis/bladder pain syndrome (IC/BPS) may be bladder-centric, with afferent nerve hyperexcitability and/or due to neural central sensitization. In bladder-centric disease, the trigone’s unmyelinated nociceptive C-fibers are thought to be upregulated, suggesting this as a potential target for diagnostic modalities and for treatment with local anesthetics and chemodenervation. We propose that the transvaginal trigone treatment (T3) route of administration of such treatments should be considered in women with IC/BPS, as this approach is easier and less invasive than cystoscopy. For T3, or other bladder-centric treatments to be successful, patient selection should attempt to exclude patients with predominantly neural central sensitization.