• Yong Huang, Minzhi Su, Chi Zhang, Hailun Zhan, Fei Yang, Zhentao Gao, Xiangfu Zhou, and Bolong Liu.
• Department of Urology, the Third Affiliated Hospital of Sun Yat-Sen University, Guangzhou, China.
• Eur J Pain. 2022 Jul 1; 26 (6): 1234-1244.

BackgroundBladder pain syndrome/interstitial cystitis (BPS/IC) is a refractory disease accompanied by bladder-related pain and hyperactivity. Studies have shown that the translocator protein (TSPO) modulates neuroinflammation and central sensitisation associated with pain. Moreover, we previously demonstrated that brain-derived neurotrophic factor (BDNF) regulates neuroinflammation and mechanical allodynia in cyclophosphamide (CYP)-induced cystitis through activation of glial cells. Here, we aimed to explore whether activation of TSPO attenuates mechanical allodynia and bladder dysfunction by regulating BDNF induced neuroinflammation in a CYP-induced cystitis model.MethodsInjection of CYP was performed to form a rat model of BPS/IC. The expression of TSPO was regulated by intrathecal injection of the TSPO agonist Ro5-4864. The von Frey filament test was applied to evaluate suprapubic allodynia. Bladder function was assessed using filling cystometry. Western blotting was used to detect the expression of TSPO, BDNF, GFAP, Iba-1, p-p38, p-JNK, TNF-α, and IL-1β, and double immunofluorescence was performed to localise TSPO in the L6-S1 spinal dorsal horn (SDH).ResultsTSPO was activated in the SDH after CYP injection and was primarily colocalised with astrocytes. Ro5-4864 reversed mechanical allodynia and bladder dysfunction induced by CYP. Moreover, the upregulation of BDNF and activation of astrocytes and microglia was suppressed by Ro5-4864, resulting in downregulation of p-p38, p-JNK, TNF-α, and IL-1β.ConclusionsRo5-4864 alleviated mechanical allodynia and bladder dysfunction in the CYP model, possibly by inhibiting the elevation of BDNF and consequent activation of astrocytes and microglia induced neuroinflammation. TSPO may be a potential target for the treatment of BPS/IC.SignificanceThis study examined the mechanism underlying the ability of the translocator protein to modulate bladder pain syndrome/interstitial cystitis.© 2022 European Pain Federation - EFIC®.

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