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Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.

ABSTRACT: Pre-clinical studies have shown that spinal cord epidural stimulation (scES) at the level of pelvic and pudendal nerve inputs/outputs (L5-S1) alters storage and/or emptying functions of both the bladder and bowel. The current mapping experiments were conducted to investigate scES efficacy at the level of hypogastric nerve inputs/outputs (T13-L2) in male and female rats under urethane anesthesia. As found with L5-S1 scES, T13-L2 scES at select frequencies and intensities of stimulation produced an increase in inter-contraction interval (ICI) in non-injured female rats but a short-latency void in chronic T9 transected rats, as well as reduced rectal activity in all groups. However, the detrusor pressure during the lengthened ICI (i.e., urinary hold) remained at a low pressure and was not elevated as seen with L5-S1 scES, an effect that's critical for translation to the clinic as high fill pressures can damage the kidneys. Furthermore, T13-L2 scES was shown to stimulate voiding post-transection by increasing bladder activity while also directly inhibiting the external urethral sphincter, a pattern necessary to overcome detrusor-sphincter dyssynergia. Additionally, select scES parameters at T13-L2 also increased distal colon activity in all groups. Together, the current findings suggest that optimization of scES for bladder and bowel will likely require multiple electrode cohorts at different locations that target circuitries coordinating sympathetic, parasympathetic and somatic outputs.

SUBMITTER: Hoey RF

PROVIDER: S-EPMC8826941 | biostudies-literature | 2022 Feb

REPOSITORIES: biostudies-literature

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Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.

Hoey Robert F RF Medina-Aguiñaga Daniel D Khalifa Fahmi F Ugiliweneza Beatrice B Wang Dengzhi D Zdunowski Sharon S Fell Jason J Naglah Ahmed A El-Baz Ayman S AS Herrity April N AN Harkema Susan J SJ Hubscher Charles H CH

Scientific reports 20220208 1

Pre-clinical studies have shown that spinal cord epidural stimulation (scES) at the level of pelvic and pudendal nerve inputs/outputs (L5-S1) alters storage and/or emptying functions of both the bladder and bowel. The current mapping experiments were conducted to investigate scES efficacy at the level of hypogastric nerve inputs/outputs (T13-L2) in male and female rats under urethane anesthesia. As found with L5-S1 scES, T13-L2 scES at select frequencies and intensities of stimulation produced a ...[more]

PMID: 35136100

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Project description:Epidural electrical stimulation can restore limb motor function after spinal cord injury by reactivating the surviving neural circuits. In previous epidural electrical stimulation studies, single electrode sites and continuous tetanic stimulation have often been used. With this stimulation, the body is prone to declines in tolerance and locomotion coordination. In the present study, rat models of complete spinal cord injury were established by vertically cutting the spinal cord at the T8 level to eliminate disturbance from residual nerve fibers, and were then subjected to epidural electrical stimulation. The flexible extradural electrode had good anatomical topology and matched the shape of the spinal canal of the implanted segment. Simultaneously, the electrode stimulation site was able to be accurately applied to the L2-3 and S1 segments of the spinal cord. To evaluate the biocompatibility of the implanted epidural electrical stimulation electrodes, GFAP/Iba-1 double-labeled immunofluorescence staining was performed on the spinal cord below the electrodes at 7 days after the electrode implantation. Immunofluorescence results revealed no significant differences in the numbers or morphologies of microglia and astrocytes in the spinal cord after electrode implantation, and there was no activated Iba-1+ cell aggregation, indicating that the implant did not cause an inflammatory response in the spinal cord. Rat gait analysis showed that, at 3 days after surgery, gait became coordinated in rats with spinal cord injury under burst stimulation. The regained locomotion could clearly distinguish the support phase and the swing phase and dynamically adjust with the frequency of stimulus distribution. To evaluate the matching degree between the flexible epidural electrode (including three stimulation contacts), vertebral morphology, and the level of the epidural site of the stimulation electrode, micro-CT was used to scan the thoracolumbar vertebrae of rats before and after electrode implantation. Based on the experimental results of gait recovery using three-site stimulation electrodes at L2-3 and S1 combined with burst stimulation in a rat model of spinal cord injury, epidural electrical stimulation is a promising protocol that needs to be further explored. This study was approved by the Animal Ethics Committee of Chinese PLA General Hospital (approval No. 2019-X15-39) on April 19, 2019.

Project description:BackgroundEpidural anaesthesia is one of the most commonly used locoregional techniques in ruminants. The lumbosacral epidural technique is reasonably easy to perform and requires low volumes of local anaesthetic drug to allow procedures caudal to the umbilicus. However, surgical procedures in the flank of the animal would require an increased volume of drugs. The anaesthetized area provided by thoracic epidural technique is larger than the lumbosacral technique; however the former is rather challenging to perform. Therefore, access through lumbosacral area to introduce a catheter into the thoracolumbar space is a potential alternative to thoracic access. Epidural anaesthesia is achieved with local anaesthetics; opioids can be added to improve analgesia. This study aimed to evaluate the effects of 0.5% bupivacaine with or without methadone, administered through an epidural catheter inserted through the lumbosacral access and advanced to the thoracolumbar space, on thoracolumbar epidural anaesthesia in goats.MethodsSix animals received two treatments each in a randomized crossover study: BUP treatment consisted of 0.5% bupivacaine (1 mL per each 10 cm of spine column; 1 ± 0.2 mg/kg BW) and BMT treatment was the same; however 1 mL of bupivacaine was replaced by 1 mL (0.22 ± 0.03 mg/kg BW) of methadone (10 mg/mL). The treatments were administered near to T11-T12 through an epidural catheter. Motor blockade and analgesia were evaluated by electrical stimulation.ResultsHeart rate, respiratory rate, ruminal motility and rectal temperature were evaluated before and after the treatment. Motor blockade was observed on both treatments, up to 6 h post-treatment. Analgesia was observed on BUP up to 4 h and on BMT up to 6 h post-treatment. Physiological values did not change at any moment.ConclusionsBupivacaine-methadone combination promoted longer-lasting analgesia in goats compared to bupivacaine alone when administered through an epidural catheter into the thoracolumbar space.

Dataset Information

Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.

Publications

Thoracolumbar epidural stimulation effects on bladder and bowel function in uninjured and chronic transected anesthetized rats.

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