Gabapentin reduces painful bladder hypersensitivity in rats with lipopolysaccharide‐induced chronic cystitis

• Published in: Pharmacology research & perspectives 2021-02, Vol.9 (1), p.e00697-n/a
• Main Authors: Yoshizumi, Masaru, Watanabe, Chizuko, Mizoguchi, Hirokazu
• Format: Article
• Language: English
• Subjects: Abdomen; Analgesics - therapeutic use; Animals; Bladder; bladder pain syndrome; chronic cystitis; Chronic illnesses; Cystitis - chemically induced; Cystitis - drug therapy; Cystitis - pathology; Cystitis - physiopathology; Cystitis, Interstitial - chemically induced; Cystitis, Interstitial - drug therapy; Cystitis, Interstitial - pathology; Cystitis, Interstitial - physiopathology; Disease Models, Animal; Drug withdrawal; Female; gabapentin; Gabapentin - therapeutic use; Histology; Hyperalgesia; Inflammation; interstitial cystitis; Laboratory animals; Ligands; lipopolysaccharide; Lipopolysaccharides; Original; Pain; Performance evaluation; Pharmacology; Polyethylene; Rats; Rats, Sprague-Dawley; Rodents; Software; Statistical analysis; Urinary Bladder - drug effects; Urinary Bladder - pathology; Urinary Bladder - physiopathology; Urinary Bladder, Overactive - drug therapy; Urinary Bladder, Overactive - pathology; Urinary Bladder, Overactive - physiopathology
• ISSN: 2052-1707; 2052-1707
• DOI: 10.1002/prp2.697

Although interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic condition causing bladder pain and urinary symptoms, effective treatments have not been established. The aim of this study was to adapt a chronic cystitis model in rats using lipopolysaccharide (LPS), which reflects IC/BPS pathology, and characterize the model's histological and behavioral effects. Furthermore, we investigated the effect of an α2δ subunit ligand, gabapentin (GBP), on bladder hypersensitivity of rats with chronic cystitis. Cystitis models were created by repeated intravesical injections of LPS. In the histological examination, the LPS‐injected group had greater inflammatory response, fibrosis, and abnormally thick re‐epithelialization. In the LPS‐injected group, LPS prompted hyperalgesia in both the lower abdomen and hind paw regions after day 1 of the first injection compared with the saline‐injected controls, without any recovery for 21 days at least. During cystometry, the LPS‐injected group showed bladder hyperactivity at all times. Systemic administration of GBP reduced cystitis‐related pain due to chronic inflammation and reduced the increased frequency of voiding in the LPS‐injected group. These results suggest that repeated intravesical injections of LPS induce long‐lasting bladder inflammation, pain, and overactivity in rats, while GBP is effective in the management of those symptoms in this chronic cystitis model. The current study identifies a relatively simple method to develop an animal model for chronic cystitis and provides evidence that GBP may be an effective treatment option for patients with IC/BPS. This study shows the repeated intravesical injections of lipopolysaccharide (LPS) could be used to generate a model of chronic cystitis in rats, which show signs of long‐lasting bladder inflammation, pain, and overactivity. Gabapentin, a neuromodulator, effectively inhibited bladder pain and overactivity in the LPS‐induced chronic cystitis rats.