Identification and characterization of rostral ventromedial medulla (RVM) neurons synaptically connected to the urinary bladder afferents in female rats with or without neonatal cystitis

2021 ◽  
Author(s):  
Bhavana Talluri ◽  
Faith Hoelzel ◽  
Bidyut K. Medda ◽  
Maia Terashvili ◽  
Patrick Sanvanson ◽  
...  
Keyword(s):  
Urinary Bladder ◽  
Female Rats ◽  
Rostral Ventromedial Medulla ◽  
Ventromedial Medulla ◽  
Bladder Afferents ◽  
Identification And Characterization

Characterization of Biphasic Modulation of Spinal Nociceptive Transmission by Neurotensin in the Rat Rostral Ventromedial Medulla

1997 ◽  
Vol 78 (3) ◽  
pp. 1550-1562 ◽  
Author(s):  
M. O. Urban ◽  
G. F. Gebhart
Keyword(s):  
Dynamic Range ◽  
Thermal Stimulation ◽  
Rostral Ventromedial Medulla ◽  
Contrast Injection ◽  
Wide Dynamic Range ◽  
Noxious Heat ◽  
Nociceptive Transmission ◽  
Neurotensin Receptor ◽  
Ventromedial Medulla

Urban, M. O. and G. F. Gebhart. Characterization of biphasic modulation of spinal nociceptive transmission by neurotensin in the rat rostral ventromedial medulla. J. Neurophysiol. 78: 1550–1562, 1997. Modulation of spinal nociceptive transmission by neurotensin microinjected in the rostral ventromedial medulla (RVM) was examined in anesthetized, paralyzed rats. Forty-three spinal dorsal horn neurons in the L3–L5 spinal segments responding to mechanical and noxious thermal stimulation (50°C) of the plantar surface of the ipsilateral hind foot were studied. Spinal units were classified as either wide dynamic range or nociceptive specific and were located in spinal laminae I–V. Microinjection of neurotensin (0.03 pmol/0.2 μl) into the RVM produced a significant facilitation (135% of control) of spinal unit responses to noxious thermal stimulation (50°C) that lasted ∼12 min. In contrast, injection of greater doses of neurotensin (300 or 3,000 pmol) produced an inhibition of spinal unit responses to noxious heat (51.7 and 10.6% of control, respectively) that had a longer duration (60–120 min). The effects of neurotensin on wide-dynamic-range and nociceptive-specific neuron responses to noxious heat were qualitatively and quantitatively similar. Spinal unit responses to graded heating of the skin (42–50°C) were completely inhibited after microinjection of 3,000 pmol of neurotensin into the RVM. Injection of a lesser dose of neurotensin (300 pmol), however, resulted in a partial inhibition of spinal unit responses and significantly reduced the slope of the stimulus-response function to graded heating of the skin. Transection of either the ipsilateral or contralateral dorsolateral funiculus (DLF) significantly reduced the inhibition of spinal nociceptive transmission produced by neurotensin (3,000 pmol) in the RVM, whereas bilateral transection of the DLFs completely blocked the effect. In contrast, bilateral transection of the DLFs had no effect on facilitation of spinal nociception by neurotensin (0.03 pmol) in the RVM. The inhibition of spinal nociceptive transmission by neurotensin (3,000 pmol) in the RVM was completely blocked by injection of the nonpeptide neurotensin receptor antagonist SR48692 (30 fmol) into the RVM 10 min before neurotensin. To confirm a specific block of neurotensin-receptor-mediated effects by the antagonist, a subsequent injection of l-glutamate into the RVM was performed. l-Glutamate (100 nmol) was found to inhibit the nociceptive responses of those spinal units whose responses were no longer inhibited by neurotensin. In contrast, injection of SR48692 (30 fmol) into the RVM failed to block the facilitation of spinal unit responses to noxious heat produced by a subsequent injection of neurotensin (0.03 pmol) into the same site. The present series of experiments demonstrate a specific role for neurotensin in the RVM in the modulation of spinal nociceptive transmission, because the peptide was found to both facilitate and inhibit spinal neuron responses to noxious thermal stimulation. Additionally, the facilitatory and inhibitory effects of neurotensin appear to occur via interaction with multiple neurotensin receptors in the RVM that activate independent systems that descend in the ventrolateral funiculi and DLFs, respectively. The results from these experiments are consistent with prior studies demonstrating that the RVM both facilitates and inhibits spinal nociceptive transmission, and they complement previous work showing that neurotensin in the RVM modulates spinal nociceptive behavioral responses.

scholarly journals Physiological properties of pain-modulating neurons in rostral ventromedial medulla in female rats, and responses to opioid administration

2021 ◽  
Vol 10 ◽  
pp. 100075
Author(s):  
Gwen Hryciw ◽  
Caitlynn C. De Preter ◽  
Jennifer Wong ◽  
Mary M. Heinricher
Keyword(s):  
Female Rats ◽  
Rostral Ventromedial Medulla ◽  
Physiological Properties ◽  
Opioid Administration ◽  
Ventromedial Medulla

Oestradiol dampens reflex-related activity of on- and off-cells in the rostral ventromedial medulla of female rats

Neuroscience ◽  
2004 ◽  
Vol 125 (4) ◽  
pp. 1061-1068 ◽  
Author(s):  
R.M Craft ◽  
M.M Morgan ◽  
D.A Lane
Keyword(s):  
Female Rats ◽  
Rostral Ventromedial Medulla ◽  
Related Activity ◽  
Ventromedial Medulla ◽  
On And Off Cells

Colonic irritation in the rat sensitizes urinary bladder afferents to mechanical and chemical stimuli: an afferent origin of pelvic organ cross-sensitization

2006 ◽  
Vol 290 (6) ◽  
pp. F1478-F1487 ◽  
Author(s):  
Elena E. Ustinova ◽  
Matthew O. Fraser ◽  
Michael A. Pezzone
Keyword(s):  
Substance P ◽  
Urinary Bladder ◽  
Receptive Fields ◽  
Pelvic Organ ◽  
Female Rats ◽  
Sprague Dawley ◽  
Trinitrobenzenesulfonic Acid ◽  
C Fibers ◽  
Bladder Afferents ◽  
Chemical Stimuli

Chronic pelvic pain (CPP) disorders frequently overlap. We have demonstrated that acute and chronic colonic irritation can lead to neurogenic cystitis. We hypothesize that acute colonic irritation can sensitize urinary bladder afferents to mechanical and chemical stimuli. Single-unit afferent activity was recorded from fine filaments of the pelvic nerve in urethane-anesthetized Sprague-Dawley female rats before and 1 h after intracolonic administration of trinitrobenzenesulfonic acid (TNBS). Only spontaneously active afferents with receptive fields in the bladder and conduction velocities <2.5 m/s (unmyelinated C-fibers) were studied. Mechanical sensitivity was tested by bladder distension (BD) during saline infusion, whereas chemical sensitivity was tested with intravesical capsaicin, bradykinin, or substance P. Colonic irritation increased the resting firing rate of bladder afferents twofold (1.0 ± 0.2 vs. 0.49 ± 0.2 impulses/s, P < 0.05). Moreover, at low-pressure BDs (10–20 mmHg), a greater percentage of afferents exhibited increased activity following TNBS (73 vs. 27%, P < 0.05). Although the magnitude of the afferent response to BD was unchanged at low pressures, the response was greatly enhanced at pressures 30 mmHg and above (2.36 ± 0.56 vs. 8.55 ± 0.73 impulses/s, P < 0.05). Responses to capsaicin, bradykinin, and substance P were also significantly enhanced following TNBS, and all responses were blocked by bladder denervation. In rats, colonic irritation sensitizes urinary bladder afferents to noxious mechanical and chemical stimuli. Interruption of the neural input to the bladder minimized this effect, suggesting a local afferent pathway from the colon. Thus, the overlap of CPP disorders may be a consequence of pelvic afferent cross-sensitization.

scholarly journals Extracellular adenosine 5’-triphosphate concentrations changes in rat spinal cord associated with the activation of urinary bladder afferents. A microdialysis study

2016 ◽  
Vol 14 (4) ◽  
pp. 541-546
Author(s):  
Jeová Nina Rocha ◽  
Keyword(s):  
Spinal Cord ◽  
Urinary Bladder ◽  
Chemical Activation ◽  
Female Rats ◽  
Microdialysis Probe ◽  
Primary Afferent ◽  
Extracellular Adenosine ◽  
Bladder Distension ◽  
Bladder Distention ◽  
Bladder Afferents

ABSTRACT Objective To determine adenosine 5’-triphosphate levels in the interstice of spinal cord L6-S1 segment, under basal conditions or during mechanical and chemical activation of urinary bladder afferents. Methods A microdialysis probe was transversally implanted in the dorsal half of spinal cord L6-S1 segment in female rats. Microdialysate was collected at 15 minutes intervals during 135 minutes, in anesthetized animals. Adenosine 5’-triphosphate concentrations were determined with a bioluminescent assay. In one group of animals (n=7) microdialysate samples were obtained with an empty bladder during a 10-minutes bladder distension to 20 or 40cmH2O with either saline, saline with acetic acid or saline with capsaicin. In another group of animals (n=6) bladder distention was performed and the microdialysis solution contained the ectonucleotidase inhibitor ARL 67156. Results Basal extracellular adenosine triphosphate levels were 110.9±35.34fmol/15 minutes, (mean±SEM, n=13), and bladder distention was associated with a significant increase in adenosine 5’-triphosphate levels which was not observed after bladder distention with saline solution containing capsaicin (10µM). Microdialysis with solution containing ARL 67156 (1mM) was associated with significantly higher extracellular adenosine 5’-triphosphate levels and no further increase in adenosine 5’-triphosphate was observed during bladder distension. Conclusion Adenosine 5’-triphosphate was present in the interstice of L6-S1 spinal cord segments, was degraded by ectonucleotidase, and its concentration increased following the activation of bladder mechanosensitive but not of the chemosensitive afferents fibers. Adenosine 5’-triphosphate may originate either from the central endings of bladder mechanosensitive primary afferent neurons, or most likely from intrinsic spinal neurons, or glial cells and its release appears to be modulated by capsaicin activated bladder primary afferent or by adenosine 5’-triphosphate itself.

Kappa opioid receptors in the rostral ventromedial medulla of male and female rats

2006 ◽  
Vol 500 (3) ◽  
pp. 465-476 ◽  
Author(s):  
Carrie T. Drake ◽  
Andrew X. De Oliveira ◽  
Jonathan A. Harris ◽  
Denise M. Connor ◽  
Clayton W. Winkler ◽  
...  
Keyword(s):  
Opioid Receptors ◽  
Female Rats ◽  
Rostral Ventromedial Medulla ◽  
Kappa Opioid Receptors ◽  
Kappa Opioid ◽  
Male And Female ◽  
Male And Female Rats ◽  
Ventromedial Medulla

Kappa Opioid Receptor (KOR) and GAD67 Immunoreactivity Are Found in off and neutral Cells in the Rostral Ventromedial Medulla

2006 ◽  
Vol 96 (6) ◽  
pp. 3465-3473 ◽  
Author(s):  
Clayton W. Winkler ◽  
Sam M. Hermes ◽  
Charles I. Chavkin ◽  
Carrie T. Drake ◽  
Shaun F. Morrison ◽  
...  
Keyword(s):  
Opioid Receptor ◽  
Cell Activity ◽  
Cell Types ◽  
Kappa Opioid Receptor ◽  
Rostral Ventromedial Medulla ◽  
Kappa Opioid ◽  
Nociceptive Reflex ◽  
Ventromedial Medulla ◽  
Functional Classes

This study combines functional and anatomical characterization of neurons in the rostral ventromedial medulla (RVM) to show distinct neurochemical phenotypes between functional classes of neurons. The RVM contains three functional classes of neurons: off cells show a pause in spontaneous activity prior to a nociceptive withdrawal reflex; on cell activity increases prior to a nociceptive reflex; and neutral cell activity does not change significantly during the nociceptive reflex. We determined if serotonin, glutamate decarboxylase (GAD67), or the kappa opioid receptor (KOR) were differentially located within these cell types as predicted by previous studies. In this study, RVM neurons were recorded extracellularly, functionally characterized, and juxtacellularly labeled with biotinamide. Fixed sections were processed for detection of biotinamide and immunfluorescence either for serotonin or for KOR and GAD67. In the first study, serotonin was found exclusively in a subset of neutral cells (33%). These data substantiate previous findings that serotonin is found in some neutral cells whose role in nociception remains unclear. In the second study, we found KOR immunoreactivity in most off (86%) and neutral (80%) cells but rarely in on (13%) cells. We also found GAD67 immunoreactivity in most off (93%) and neutral cells (80%) but less frequently in on cells (63%). Most KOR-immunoreactive cells (16 of 17) also contained GAD67 immunoreactivity regardless of cell classification. These findings support the hypothesis that KOR agonists directly inhibit off and neutral cell activity. The majority of the off and neutral cells are GABAergic, and some on cells are also GABAergic.

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