Urinary Bladder Irritation Alters Efficacy of Vagal Stimulation on Rostral Medullary Neurons in Chronic T8 Spinalized Rats

Abstract

The presence of pelvic visceral inputs to neurons in the rostral medulla that are responsive to electrical stimulation of the abdominal branches of the vagus nerve (VAG-abd) was investigated in a complete chronic T8 spinal transection rat model. Using extracellular electrophysiological recordings from single medullary reticular formation (MRF) neurons, 371 neurons in 15 rats responsive to pinching the ear (search stimulus) were tested for somato-visceral and viscero-visceral convergent responses to stimulation of the following nerves/territories: VAG-abd, dorsal nerve of the penis, pelvic nerve, distention of urinary bladder and colon, penile stimulation, urethral infusion, and touch/pinch of the entire body surface. In addition to these mechanical and electrical stimuli, a chemical stimulus applied to the bladder was assessed as well. Of the total neurons examined, 205 were tested before and 166 tested beginning 20 min after application of a chemical irritant (2% acetic acid) to the urinary bladder (same rats used pre/post irritation). As with intact controls, many ear-responsive MRF neurons responded to the electrical stimulation of VAG-abd. Although MRF neuron responses failed to be evoked with direct (mechanical and electrical nerve) pelvic visceral stimuli, acute chemical irritation of the urinary bladder produced a significant increase in the number of MRF neurons responsive to stimulation of VAG-abd. The results of this study indicate a central effect that potentially relates to some of the generalized below level pelvic visceral sensations that have been documented in patients with complete spinal cord injury.

The effect of spinal cord injury on vagal afferents.

“…In both studies where there were increases in P2X3 expression, the injury model used resulted in some neurons that would be potentially "uninjured". To assess these differences, activating transcription factor Even though contact between the vagus nerve and its peripheral targets has not been severed, there is an overall effect of injury on the vagal afferent neurocircuitry Berkley, 1995, Kaddumi andHubscher, 2007) and the increased P2X3 expression seen in the NG here may help to improve our understanding of the indirect effect on the vagal system after injury. For instance, the increased P2X3-ir following SCI may be attributed to an inflammatory reaction of the system due to the nature of the injury itself.…”

“…For example, it has been hypothesized that spinal afferents are responsible for conveying noxious mechanical information, while noxious chemical stimuli are conveyed via vagal afferents (Schuligoi et al, 1998, Michl et al, 2001, Page et al, 2002, Holzer, 2003, Sugiura et al, 2005, Kaddumi and Hubscher, 2007. Aside from communicating differential stimuli from the periphery, both vagal and spinal projections likely converge in the brainstem.…”

“…All surgeries were performed under aseptic conditions and the body temperature was maintained within the range of 36-37ºC via a warm water recirculator (Gaymar T/Pump, Gaymar Industries Inc, Orchard Park, NY) throughout the surgery and recovery period. Following our previously published protocol (Kaddumi and Hubscher, 2007) once per day for 5 days to prevent bladder infections. After surgery each animal was housed individually.…”

“…The slides were then stained with both Luxol fast blue and cresyl violet (Kluver-Barrera method) to observe myelin and Nissl substance, respectively. Spot Advanced software (Diagnostic Instruments, Sterling Heights, MI) and the Nikon E400 microscope were used to image the lesion cavity and verify the completeness of the spinal transection (Kaddumi and Hubscher, 2007).…”

“…Although they are typically not responders to visceral stimuli within the noxious range (Ozaki et al, 1999), previous data from our lab and that of others suggest otherwise. For example, while spinal afferents may be responsible for relaying mechanical nociceptive information, vagal afferents may play more of a predominant role in conveying chemical nociceptive stimuli, thus contributing to disease-related conditions stemming from visceral hyperalgesia (Schuligoi et al, 1998, Michl et al, 2001, Page et al, 2002, Holzer, 2003, Sugiura et al, 2005, Kaddumi and Hubscher, 2007. Therefore, besides the known role of vagal afferents in relaying homeostatic information to the brain, the population of vagal afferents that also are IB4+ may be involved in visceral nociceptive processing (based on the putative role of the majority of DRG IB4 binding neurons (Vulchanova et al, 2001, Petruska et al, 2002).…”