Chronic stable recording of physiologically evoked neural activity in a mixed autonomic nerve in awake, freely moving normal and experimental cystitis rats

Closed-loop control over bladder function, for conditions such as neurogenic bladder dysfunction, requires real-time monitoring of bladder state. Here, we assessed the ability of a novel recording and analysis technique to extract neural activity from awake rats as a quasi-real-time feedback biomarker of bladder fullness in normal and chronic cystitis models. Adult male rats (n = 12) were implanted with a four-electrode planar array and the bladder instrumented for continuous-flow cystometry over 2 weeks. In three rats, bladder inflammation was induced using cyclophosphamide (CYP, 75–100 mg/kg, i.p.). Neural recordings were made during awake cystometry, and extracted Aδ afferent activity was correlated with bladder pressure. In control rats (n = 9), there was a strong, stable correlation of integrated Aδ activity with bladder pressure during filling at 1 week (R2: 0.55 ± 0.04) and 2 weeks (R2: 0.57 ± 0.04; p > 0.05). In CYP-cystitis rats (days 9, 11, and 14), there was no difference in this correlation (week 2: 0.54 ± 0.031; p > 0.05). Taken together, data suggest the recording and analysis technology remained stable in awake, freely moving normal rats and during 2 weeks of chronic implantation. Furthermore, data show potential that abnormal activation of nociceptive afferents in cystitis rats, which causes an increase in baseline activity, does not weaken correlation of Aδ activity with bladder pressure. In conclusion, this feasibility study is a promising first study step for the translation of closed-loop technology for bladder control for neurogenic bladder dysfunction.