Spinal cord stimulation modulates intraspinal colorectal visceroreceptive transmission in rats

Abstract

Previous studies have shown that spinal cord stimulation (SCS) of upper lumbar segments decreases visceromotor responses to mechanical stimuli in a sensitized rat colon and reduces symptoms of irritable bowel syndrome in patients. SCS applied to the upper cervical spinal dorsal column reduces pain of chronic refractory angina. Further, chemical stimulation of C1-C2 propriospinal neurons in rats modulates the responses of lumbosacral spinal neurons to colorectal distension. The present study was designed to compare the effects of upper cervical and lumbar SCS on activity of lumbosacral neurons receiving noxious colorectal input. Extracellular potentials of L6-S2 spinal neurons were recorded in pentobarbital anesthetized, paralyzed and ventilated male rats. SCS (50 Hz, 0.2 ms) at low intensity (90% of motor threshold) was applied to the dorsal column of upper cervical (C1-C2) or upper lumbar (L2-L3) ipsilateral spinal segments. Colorectal distension (CRD, 20, 40, 60 mmHg, 20 s) was produced by air inflation of a latex balloon. Results showed that SCS applied to L2-L3 and C1-C2 segments significantly reduced the excitatory responses to noxious CRD from 417.6±68.0 imp to 296.3±53.6 imp (P<0.05, n=24) and from 336.2±64.5 imp to 225.0±73.3 imp (P<0.05, n= 18), respectively. Effects of L2-L3 and C1-C2 SCS lasted 10.2±1.9 min and 8.0 ±0.9 min after offset of CRD. Effects of SCS were observed on spinal neurons with either high or low threshold excitatory responses to CRD. However, L2-L3 or C1-C2 SCS did not significantly affect inhibitory neuronal responses to CRD. C1-C2 SCS-induced effects were abolished by cutting the C7-C8 dorsal column but not by spinal transection at cervicomedullary junction. These data demonstrated that upper cervical or lumbar SCS modulated responses of lumbosacral spinal neurons to noxious mechanical stimulation of the colon, thereby, proved two loci for a potential therapeutic effect of SCS in patients with irritable bowel syndrome and other colonic disorders.

Neuromodulation of Thoracic Intraspinal Visceroreceptive Transmission by Electrical Stimulation of Spinal Dorsal Column and Somatic Afferents in Rats

“…These data are similar to a previous observation in lumbosacral spinal cord in rats, in which L2-L3 SCS inhibits 67% L6-S2 spinal neurons responding to noxious colorectal distension. 43 However, C3-C5 SCS reduces excitatory responses of 86% of upper thoracic STT neurons to intracardiac injection of bradykinin and of all STT neurons excited by electrical stimulation of cardiopulmonary sympathetic afferent fibers in monkeys. 6 The different species, neuronal classifications and visceral stimuli tested might contribute to the differences in these investigations.…”

“…The dorsal column pathway is likely candidate because transection of the dorsal column at the C7-C8, but not transection of the spinal cord at the spinomedullary junction, significantly reduces the ability of C1-C2 SCS to suppress neuronal activity in lumbosacral spinal neurons to noxious colorectal distension. 43 The most likely mechanism is SCS activation of action potentials in large primary afferent fibers that are transmitted antidromically to the collaterals in the gray matter of the T3-T4 segments. 28, 29 The collaterals then release transmitters that directly and/or indirectly suppress the activity of spinal neurons receiving cardiac and esophageal nociceptive input.…”

“…It should also be noted that the C1-C2 segments are also considered a source of important propriospinal regulation of visceral sensory processing in more caudal spinal segments. 7,13,34,39,40,41,43 However, this pathway does not appear to play a key role because transection of the C7-C8 dorsal columns, but not application of ibotenic acid to the C1-C2 segments markedly attenuated the effects of SCS on lumbosacral spinal neurons. 43 Thus, it is suggested that the stimulation of the dorsal columns rather than spinal neurons at C1-C2 segments modulated the activity of T3 spinal neurons receiving cardiac and esophageal inputs.…”

“…SCS at upper cervical and lumber segments also suppress responses of lumbosacral spinal neurons to noxious colonic distension and attenuate a nociceptive visceromotor reflex produced by colorectal distension in rats with or without colonic hypersensitivity. 18,19,43 Various manipulations that activate peripheral somatic afferents, e.g. transcutaneous electrical nerve stimulation (TENS), manual acupuncture or electroacupuncture, direct or percutaneous peripheral nerve stimulation, and massage therapy, have been commonly used for treatment and relief of some visceral pains.…”

Spinal Cord Stimulation for Intractable Visceral Pain due to Chronic Pancreatitis

“…Application of spinal cord stimulation (SCS) for the neuropathic pain, such as failed back surgery syndrome, angina pectoris, peripheral nerve injury pain, causalgia, reflex sympathetic dystrophy have been shown good outcome [3][4][5]7,8,16) . In addition, spinal cord stimulation suppresses visceral response to colon distension in an animal model 3,12,13,16) . Case series in the literature report an effective outcome of SCS on intractable visceral pain [3][4][5]16) .…”