Parametric Assessment of Spinal Cord Stimulation on Bladder Pain-Like Responses in Rats

Abstract

Objectives: Spinal cord stimulation (SCS) for the treatment of pelvic visceral pains has been understudied and underused. The goal of the current study was to examine multiple stimulation parameters of SCS to determine optimal settings for the inhibition of responses to urinary bladder distension (UBD) in animal models of bladder pain as a guide for human studies.

Materials and methods: Adult, female isoflurane/urethane-anesthetized rats underwent a T13/L1 mini-laminectomy sufficient to implant an SCS paddle lead for neuromodulation. Silver wire electrodes were inserted into the external oblique musculature. A 22-gauge angiocatheter was placed transurethrally into the bladder and used to deliver phasic, air UBDs at pressures of 10 to 60 mm Hg and visceromotor (abdominal contractile) electromyographic responses to UBD measured in the presence and absence of SCS. Electromyographic activity was quantified using standard differential amplification and rectification. Parameter settings for SCS included both conventional (10, 50, 100 Hz) and high frequency (1,000, 5,000, and 10,000 Hz) biphasic square wave pulses with 50 to 200 μs durations. To create states of hypersensitivity, pretreatment of adult rats included an intravesical zymosan infusion 24 hours before testing with and without a preceding episode of neonatal bladder inflammation.

Results: Low frequency (10, 50, and 100 Hz) 200 μs biphasic pulses at submotor thresholds demonstrated inhibition of visceromotor responses (VMRs) to UBD in rats made hypersensitive to UBD by a protocol that included neonatal cystitis. Onset of inhibitory effects occurred within 20 minutes of beginning SCS. Otherwise, SCS at all other parameters studied and in other tested rat models produced either no significant effect or augmentation of VMRs.

Conclusions: Demonstration of inhibitory effects of SCS in a clinically relevant model of bladder pain suggests the potential utility of this therapy in patients with painful bladder disorders.

Keywords: Bladder pain syndrome; interstitial cystitis; neonatal cystitis; neuromodulation; zymosan.