AIMTo explore the cerebral cortex mechanism of visceral nociceptive sensation and its characteristics on the cell level, we investigated the membrane electrical properties of 176 stimulus-relative neurons of greater splanchnic nerve (GSN) in anterior cingulate gyrus (ACG) of 20 adult healthy cats.

METHODSWe used intracellular recording techniques of glass microelectrode and injected polarizing current into the neurons in ACG.

RESULTSAmong 176 neurons, 148 were visceral nociceptive neurons (VNNs) and 28 non-visceral nociceptive neurons (NVNNs). The membrane resistance (Rm), time constant (tau), membrane capacity (Cm), and the I-V curve of both VNNs and NVNNs in ACG were significantly different. The discharge frequency and amplitude of both VNNs and NVNNs produced by injecting depolarized current were different, too.

CONCLUSIONThe results suggest that structure of cell membrane, volume of the soma, and other aspects of morphology between VNNs and NVNNs in ACG may have significant differences. The results also might provide progressively experimental evidence for specific theory of pain sensation.

Animals ; Cats ; Gyrus Cinguli ; cytology ; physiology ; Membrane Potentials ; Nociceptors ; physiology ; Splanchnic Nerves ; physiology ; Visceral Afferents ; physiology

The physiological mechanism underlying the acupoint sensitization was evaluated systemically by using the method of electric physiology at spinal cord, medulla, and thalamus levels; the dynamic change of acupoint from the relative "silence" to the relative "activation" function was explained through the study on the dynamic process of acupoint sensitization; the biological process of the therapeutic effect of acupoint stimulation was illuminated through the research of the central mechanism underlining the dose effect relationship between the sensitive acupoint and the related brain area, thus scientific evidence for the functional link between the acupoint and internal organs as well as the nature of the acupoint were provided.
Acupuncture Points ; Acupuncture Therapy ; Animals ; Humans ; Moxibustion ; Nociceptors ; physiology ; Sensation ; Viscera ; innervation ; physiology ; Visceral Afferents ; physiology

BACKGROUND/AIMS: Mesenteric afferent nerves (MANs) play a pivotal role in the visceral-nociceptive perception. Inappropriate activation of MANs may be involved in the pathogenesis of post-infectious irritable bowel syndrome (PI-IBS). However, the underlying mechanisms remain unclear. We assessed the effects of mucosal mediators from different bowel segments of guinea pigs with PI-IBS on MAN firing and the role of mast cells. METHODS: PI-IBS was induced in guinea pigs by Trichinella spiralis infection. Inflammation in terminal ileum, proximal and distal colon was scored with hematoxylin-eosin staining, and mast cell infiltration was assessed with immunofluorescence. We determined the effects of supernatant extracted from the mucosa of different bowel segments of PI-IBS on MANs activity, and assessed the role of mast cells in this process. RESULTS: Eight weeks after infection, intestinal inflammation resolved, whereas mast cell numbers increased significantly in terminal ileum and proximal colon (P < 0.05) compared with findings in controls. Mucosal supernatant from different bowel segments of PI-IBS models, but not from controls, significantly enhanced the frequency of MAN firing (terminal ileum 41.01 +/- 7.60 Hz vs. 26.55 +/- 0.67 Hz, P = 0.001; proximal colon 45.90 +/- 11.20 Hz vs. 30.88 +/- 6.92 Hz, P = 0.002; distal colon 48.25 +/- 9.70 Hz vs. 29.47 +/- 6.13 Hz, P < 0.001). In addition, the excitatory effects were inhibited by mast cell stabilizer Nasmil (terminal ileum, 32.71 +/- 2.52 Hz, P = 0.030; proximal colon, 30.94 +/- 4.44 Hz, P = 0.002; distal colon, 27.15 +/- 5.83 Hz, P < 0.001). CONCLUSIONS: Supernatant from the intestinal mucosa of different bowel segments of PI-IBS models markedly enhanced the MAN firing in a mast cell-dependent manner, indicating that mast cell-mediated MAN activation plays an important role in the pathogenesis of PI-IBS.
Animals ; Colon ; Fires ; Fluorescent Antibody Technique ; Guinea Pigs* ; Hyperalgesia ; Ileum ; Inflammation ; Intestinal Mucosa ; Irritable Bowel Syndrome* ; Mast Cells ; Mucous Membrane ; Trichinella spiralis ; Visceral Afferents

Visceral afferent nerve fibers containing substance P or calcitonin gene-related peptide (CGRP) are distributed in the bladder wall, and are known to be stimulated by and then desensitized by capsaicin. Recently, there have been some reports on the effectiveness of intravesical capsaicin administration for the treatment of hypersensitive lower urinary tract disorder or neurogenic bladder. In this study, the effects of intravesical capsaicin on the substance P or CGRP immunoreactivities in the spinal dorsal horn were investigated and the mechanism of capsaicin treatment for bladder disorders was revealed. After intravesical administration of capsaicin, the substance P and CGRP immunoreactive areas were measured at the dorsal horn of L4 and S1 spinal cord. Before capsaicin treatment, the substance P immuno- reactive area was 2.61+/-0.78 x 105 mm2 in L4 and 1.66+/-0.49 x 105 mm2 in S1. The substance P immunoreactivity was markedly reduced 1~2 weeks after capsaicin treatment in both L4 and S1 spinal cord. The CGRP immunoreactive area was 1.74+/-0.52 x 105 mm2 in L4 and 1.14+/-0.69 x 105 mm2 in S1, but was not reduced after capsaicin treatment. Therefore, capsaicin administered intravesically desensitizes nerve fibers containing substance P and consequently suppresses pain and voiding reflex.
Administration, Intravesical ; Animals ; Calcitonin Gene-Related Peptide ; Capsaicin* ; Horns* ; Nerve Fibers ; Rats* ; Reflex ; Spinal Cord ; Substance P ; Urinary Bladder ; Urinary Bladder, Neurogenic ; Urinary Tract ; Visceral Afferents

The purpose of this study was to determine the effect of intrarenal artery injection of L-arginine on multi- and single-unit spontaneous discharges of renal afferent nerve fibers in anesthetized rabbits. The results obtained are as follows: (1) intrarenal artery injection of L-arginine (0.05, 0.24, and 0.48 mmol/kg) decreased the renal afferent nerve activity (ARNA) in a dose-dependent manner with arterial pressure unchanged; (2) pretreatment with a nitric oxide synthase inhibitor L-NAME (N6-nitro-L-arginine methylester, 0.11 mmol/kg), completely abolished the effect of L-arginine; and (3) intrarenal artery injection of a nitric oxide donor SIN-1 (3-morpholinosydnonimine, 3.75 micromol/kg) also resulted in an inhibition of ARNA. The results suggest that intrarenal artery injection of NO precursor (L-arginine) and donor (SIN-1) can inhibit ARNA in anesthetized rabbits.
Animals ; Arginine ; administration & dosage ; pharmacology ; Depression, Chemical ; Electrophysiological Phenomena ; Female ; Injections, Intra-Arterial ; Kidney ; innervation ; Male ; Nerve Fibers ; drug effects ; physiology ; Rabbits ; Renal Artery ; Visceral Afferents ; physiology

Nausea and emesis are a major side effect and obstacle for chemotherapy in cancer patients. Employ of antiemetic drugs help to suppress chemotherapy-induced emesis in some patients but not all patients. Ginger, an herbal medicine, has been traditionally used to treat various kinds of diseases including gastrointestinal symptoms. Ginger is effective in alleviating nausea and emesis, particularly, for cytotoxic chemotherapy drug-induced emesis. Ginger-mediated antiemetic effect has been attributed to its pungent constituents-mediated inhibition of serotonin (5-HT) receptor activity but its cellular mechanism of action is still unclear. Emetogenic chemotherapy drugs increase 5-HT concentration and activate visceral vagal afferent nerve activity. Thus, 5-HT mediated vagal afferent activation is essential to provoke emesis during chemotherapy. In this experiment, water extract of ginger and its three major pungent constituent's effect on 5-HT-evoked responses were tested on acutely dispersed visceral afferent neurons with patch-clamp methods. The ginger extract has similar effects to antiemetic drug ondansetron by blocking 5-HT-evoked responses. Pungent constituents of the ginger, [6]-shogaol, [6]-gingerol, and zingerone inhibited 5-HT responses in a dose dependent manner. The order of inhibitory potency for these compounds were [6]-shogaol>[6]-gingerol>zingerone. Unlike well-known competitive 5-HT3 receptor antagonist ondansetron, all tested ginger constituents acted as non-competitive antagonist. Our results imply that ginger and its pungent constituents exert antiemetic effects by blocking 5-HT-induced emetic signal transmission in vagal afferent neurons.
Antiemetics ; Drug Therapy ; Ginger* ; Herbal Medicine ; Humans ; Nausea ; Neurons* ; Neurons, Afferent ; Ondansetron ; Receptors, Serotonin, 5-HT3 ; Serotonin* ; Visceral Afferents* ; Vomiting ; Water

PURPOSE: The clinical benefits of intravesical electrical stimulation (IVES), in patients with increased residual urine or reduced bladder capacity, have been reported. However, studies on the underlying mechanism of IVES have been limited to the Adelta afferent in healthy rats. This study investigated the changes in the calcitonin gene- related peptide (CGRP) and substance P (SP) expressions, in the lumbosacral dorsal root ganglia (DRG) and the bladder of spinalized rats, to determine the effect of IVES on the C fiber afferent nerve. MATERIALS AND METHODS: Forty Sprague-Dawley rats were divided into normal controls (n=10); IVES treated normal rats (n=10); spinalized rats (n=10) and IVES treated spinalized rats (n=10). The IVES was performed for 2 weeks (5 days a week), 3 weeks after the spinalization in the spinalized animals. All animals had their DRG removed at the lumbosacral (L5-S1) level. Changes in the CGRP and SP, at the DRG and bladder, were measured by western-blot analysis. RESULTS: The relative density of the CGRP and SP following spinalization was significantly higher than those in the controls in both the DRG and the bladder. However, IVES in the spinalized rat significantly decreased the relative density of the SP, in both the DRG and the bladder, compared to the rats with spinalization alone. IVES in the spinalized rats significantly decreased the relative density of the CGRP, in the DRG only, compared to the rats with spinalization. CONCLUSIONS: IVES significantly reduced the CGRP and SP levels in the DRG of spinalized rats, but only the SP levels in the bladder. CGRP and SP are the main factors contributing to the hyper-excitability of the micturition reflex following spinal cord injury. These results suggest that the bladder C fiber afferents are also involved in modulating the micturition reflex with IVES.
Animals ; Calcitonin ; Diagnosis-Related Groups ; Electric Stimulation* ; Ganglia, Spinal ; Humans ; Nerve Fibers, Unmyelinated ; Neuropeptides* ; Rats* ; Rats, Sprague-Dawley ; Reflex ; Specific Gravity ; Spinal Cord Injuries ; Substance P ; Urinary Bladder* ; Urination ; Visceral Afferents

Abdominal Muscles ; physiology ; Abdominal Pain ; diagnosis ; physiopathology ; Animals ; Animals, Newborn ; Colon ; innervation ; Electrodes ; Electromyography ; Female ; Pain Measurement ; methods ; Pain Threshold ; physiology ; Rats ; Rats, Sprague-Dawley ; Viscera ; Visceral Afferents ; physiology

The effects of intrarenal artery injection of capsaicin on multi- and single-unit spontaneous discharges of renal afferent nerve fibers were investigated in anesthetized rabbits. The results obtained are as follows: (1) intrarenal artery injection of capsaicin (20, 40, and 60 nmol/kg) increased the renal afferent nerve activity (ARNA) in a dose-dependent manner with unchanged arterial pressure; (2) pretreatment with ruthenium red (40 mmol/kg), a capsaicin receptor antagonist, completely abolished the effect of capsaicin; and (3) pretreatment with a nitric oxide synthase inhibitor L-NAME (N(6)-nitro-L-arginine methylester, 0.1 mmol/kg), significantly enhanced the ARNA response to capsaicin. The results suggest that intrarenal artery injection of capsaicin can activate ARNA via capsaicin receptors in anesthetized rabbits and that nitric oxide may be involved in regulating the activity of renal sensory nerve fibers as an inhibitory neurotransmitter.
Animals ; Capsaicin ; pharmacology ; Dose-Response Relationship, Drug ; Electrophysiology ; Female ; Injections, Intra-Arterial ; Kidney ; innervation ; Male ; NG-Nitroarginine Methyl Ester ; pharmacology ; Nitric Oxide ; pharmacology ; Rabbits ; Ruthenium Red ; pharmacology ; Visceral Afferents ; physiology