Spinal Cord Stimulation Attenuates Visceral Pain-Related Visceromotor Reflexes in Rodents with Cyclophosphamide-Induced Cystitis
Sources of Funding: Supported by NIH (R01 DK106181) to HH Chang.
Introduction
Interstitial cystitis/bladder pain syndrome (IC/BPS) is a chronic inflammation that results in recurring pain in the bladder and the surrounding pelvic region caused by abnormal excitability of micturition reflexes. Spinal cord stimulation (SCS) is currently in clinical use for the attenuation of neuropathic pain, and has been identified for amelioration of pain in a rodent model of colorectal distention. This study aimed to investigate the potential effect of SCS on attenuation of visceral pain-related visceromotor reflexes (VMR) in rodents with cyclophosphamide-induced cystitis.
Methods
Female Sprague-Dawley rats underwent intraperitoneal injection of cyclophosphamide (CYP, n=8) or saline (controls, n=4). 48 hours after CYP or saline injections, all rats underwent surgical preparations under urethane anesthesia. Stimulation wires were placed on the dorsal surface of the spinal segments of L2 and L3 for SCS. A PE-50 tubing was inserted into the bladder to obtain the intravesical pressure (IVP). Two wires are placed in the left external abdominal oblique muscle to record VMR. Before and after SCS (40 Hz, 0.2 ms for 25 min), VMR and maximum intravesical pressure (IVPmax) were obtained during continuous bladder infusion and isotonic bladder distention (IBD).
Results
During continuous bladder infusion (Fig 1A), the ratio of VMR threshold/IVPmax was significantly decreased in CYP rats indicating early VMR appearance compared to controls. SCS significantly increased the ratio indicating the delayed VMR appearance. During IBD with urethral occlusion, SCS delayed the latency of VMR appearance in CYP rats below the voiding thresholds at 10 and 20 cmH2O. SCS also significantly decreased VMR area under the curve (AUC) in CYP rats (Figs 1B-C).
Conclusions
SCS attenuated visceral pain-related VMR in rats with CYP-induced cystitis suggesting a role for SCS in modulating visceral nociception and hyperalgesia. SCS appears to be a potential treatment of IC/PBS.
Funding
Supported by NIH (R01 DK106181) to HH Chang.
David A Ginsberg
Larissa V Rodriguez
Huiyi Harriet Chang