GABA and enkephalin tonically alter sympathetic outflows in the rat spinal cord

Bowman, Belinda R.; Goodchild, Ann K.

doi:10.1016/j.autneu.2015.08.006

Cited by 8 publications

(10 citation statements)

References 47 publications

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“…Enkephalins are endogenous opiates that play an important role in the modulation of nociceptive information by mediating synaptic transmission in several areas of the central nervous system [ 92 , 93 ]. Most ENK present in the DHSC originates from local interneurons, although a few enkephalinergic fibers may descend from the brainstem [ 94 – 96 ] or originate from dorsal root ganglion neurons [ 97 , 98 ]. In the DHSC, ENK is highly concentrated in the neurons located in the superficial laminae I and II and is sparsely distributed in the deep laminae V–VII and around the central canal [ 99 , 100 ].…”

Section: Discussionmentioning

confidence: 99%

Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats

et al. 2016

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Transcranial direct current stimulation (tDCS) is an emerging, noninvasive technique of neurostimulation for treating pain. However, the mechanisms and pathways involved in its analgesic effects are poorly understood. Therefore, we investigated the effects of direct current stimulation (DCS) on thermal and mechanical nociceptive thresholds and on the activation of the midbrain periaqueductal gray (PAG) and the dorsal horn of the spinal cord (DHSC) in rats; these central nervous system areas are associated with pain processing. Male Wistar rats underwent cathodal DCS of the motor cortex and, while still under stimulation, were evaluated using tail-flick and paw pressure nociceptive tests. Sham stimulation and naive rats were used as controls. We used a randomized design; the assays were not blinded to the experimenter. Immunoreactivity of the early growth response gene 1 (Egr-1), which is a marker of neuronal activation, was evaluated in the PAG and DHSC, and enkephalin immunoreactivity was evaluated in the DHSC. DCS did not change the thermal nociceptive threshold; however, it increased the mechanical nociceptive threshold of both hind paws compared with that of controls, characterizing a topographical effect. DCS decreased the Egr-1 labeling in the PAG and DHSC as well as the immunoreactivity of spinal enkephalin. Altogether, the data suggest that DCS disinhibits the midbrain descending analgesic pathway, consequently inhibiting spinal nociceptive neurons and causing an increase in the nociceptive threshold. This study reinforces the idea that the motor cortex participates in the neurocircuitry that is involved in analgesia and further clarifies the mechanisms of action of tDCS in pain treatment.

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Section: Discussionmentioning

confidence: 99%

Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats

et al. 2016

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“…Doses of 5-HT (1 mol/head), ketanserin (100 nmol/head), dolasetron (100 nmol/head), and fluoxetine (3 nmol/ head) were selected according to previous studies in rats (6,7,29,32). A previous study showed that injection of bicuculline at a dose of 20 nmol in the spinal cord in rats causes muscle contractions, and thereby injection of a muscle relaxant is required (4). In this study, bicuculline was used at a dose of 1 nmol to avoid using a muscle relaxant.…”

Section: Methodsmentioning

confidence: 99%

Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats

Nakamori

Naitou

Horii

et al. 2018

American Journal of Physiology-Gastrointestinal and Liver Physi

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Colorectal motility is regulated by two defecation centers located in the brain and spinal cord. In previous studies, we have shown that administration of serotonin (5-HT) in the lumbosacral spinal cord causes enhancement of colorectal motility. Because spinal 5-HT is derived from neurons of the medullary raphe nuclei, including the raphe magnus, raphe obscurus, and raphe pallidus, we examined whether stimulation of the medullary raphe nuclei enhances colorectal motility via the lumbosacral defecation center. Colorectal pressure was recorded with a balloon in vivo in anesthetized rats. Electrical stimulation of the medullary raphe nuclei failed to enhance colorectal motility. Because GABAergic neurons can be simultaneously activated by the raphe stimulation and released GABA masks accelerating actions of the raphe nuclei on the lumbosacral defecation center, a GABA receptor antagonist was preinjected intrathecally to manifest excitatory responses. When spinal GABA receptors were blocked by the antagonist, electrical stimulation of the medullary raphe nuclei increased colorectal contractions. This effect of the raphe nuclei was inhibited by intrathecal injection of 5-hydroxytryptamine type 2 (5-HT) and type 3 (5-HT) receptor antagonists. In addition, injection of a selective 5-HT reuptake inhibitor in the lumbosacral spinal cord augmented the raphe stimulation-induced enhancement of colorectal motility. Transection of the pelvic nerves, but not transection of the colonic nerves, prevented the effect of the raphe nuclei on colorectal motility. These results demonstrate that activation of the medullary raphe nuclei causes augmented contractions of the colorectum via 5-HT and 5-HT receptors in the lumbosacral defecation center. NEW & NOTEWORTHY We have shown that electrical stimulation of the medullary raphe nuclei causes augmented contractions of the colorectum via pelvic nerves in rats. The effect of the medullary raphe nuclei on colorectal motility is exerted through activation of 5-hydroxytryptamine type 2 and type 3 receptors in the lumbosacral defecation center. The descending serotoninergic raphespinal tract represents new potential therapeutic targets against colorectal dysmotility such as irritable bowel syndrome.

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“…Retrograde tracing was carried out as described previously (Bowman and Goodchild, 2015) with the tissue used here acquired from the animals used in this previous study. Rats ( n = 12) were anesthetized with ketamine (75 mg/kg) and medetomidine (0.5 mg/kg, ip).…”

Section: Methodsmentioning

confidence: 99%

“…After 2 days, rats were reanesthetized with sodium pentobarbital (80 mg/kg ip), perfused as described above and brain and spinal cord were removed and placed fixative overnight before processing. CTB injection sites within the spinal cord were shown previously (Bowman and Goodchild, 2015).…”

Section: Methodsmentioning

confidence: 99%

“…Combined immunohistochemistry and in situ hybridization was carried out on brains and spinal cords cut coronally using a microtome (VT1200S, Leica, Wetzlar, Germany; 40 and 100 μm, respectively). Spinal cord injection sites were identified using a modified nickel intensified diaminobenzidine (DAB) reaction as described and demonstrated previously (Bowman and Goodchild, 2015).…”

Section: Methodsmentioning

confidence: 99%

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Somatostatin 2 Receptors in the Spinal Cord Tonically Restrain Thermogenic, Cardiac and Other Sympathetic Outflows

et al. 2019

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The anatomical and functional characterization of somatostatin (SST) and somatostatin receptors (SSTRs) within the spinal cord have been focused in the dorsal horn, specifically in relation to sensory afferent processing. However, SST is also present within the intermediolateral cell column (IML), which contains sympathetic preganglionic neurons (SPN). We investigated the distribution of SSTR2 within the thoracic spinal cord and show that SSTR2A and SSTR2B are expressed in the dorsal horn and on SPN and non-SPN in or near the IML. The effects of activating spinal SSTR and SSTR2 were sympathoinhibition, hypotension, bradycardia, as well as decreases in interscapular brown adipose tissue temperature and expired CO 2 , in keeping with the well-described inhibitory effects of activating SSTR receptors. These data indicate that spinal SST can decrease sympathetic, cardiovascular and thermogenic activities. Unexpectedly blockade of SSTR2 revealed that SST tonically mantains sympathetic, cardiovascular and thermogenic functions, as activity in all measured parameters increased. In addition, high doses of two antagonists evoked biphasic responses in sympathetic and cardiovascular outflows where the initial excitatory effects were followed by profound but transient falls in sympathetic nerve activity, heart rate and blood pressure. These latter effects, together with our findings that SSTR2A are expressed on GABAergic, presumed interneurons, are consistent with the idea that SST2R tonically influence a diffuse spinal GABAergic network that regulates the sympathetic cardiovascular outflow. As described here and elsewhere the source of tonically released spinal SST may be of intra- and/or supra-spinal origin.

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GABA and enkephalin tonically alter sympathetic outflows in the rat spinal cord

Cited by 8 publications

References 47 publications

Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats

Top-Down Effect of Direct Current Stimulation on the Nociceptive Response of Rats

Medullary raphe nuclei activate the lumbosacral defecation center through the descending serotonergic pathway to regulate colorectal motility in rats

Somatostatin 2 Receptors in the Spinal Cord Tonically Restrain Thermogenic, Cardiac and Other Sympathetic Outflows

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