Amylin suppresses acetic acid-induced visceral pain and spinal c-fos expression in the mouse

Tachykinins, colocalized with calcitonin gene-related peptides (CGRP) in sensory afferents, are involved in viscerosensitive responses. We investigated the role of tachykinins and CGRP in both nociceptive and visceromotor responses to inflammation. Visceral pain was assessed by abdominal muscle contractions. Gastric emptying was evaluated after gavage with reconstituted milk containing 51Cr-labeled sodium chromate. Acetic acid or 9% NaCl was injected intraperitoneally before the meal. RP-67580, SR-48968, human CGRP [hCGRP-(8-37)], or their vehicles were injected before acetic acid or saline. RP-67580, SR-48968, or their vehicles were injected before CGRP and the meal. GR-73632 or GR-76349 was injected before the meal. Acetic acids inhibited gastric emptying and increased the number of abdominal contractions. RP-67580 reduced the inhibition of gastric emptying without affecting the abdominal response. SR-48968 only reduced the acetic acid-induced increase of abdominal contractions. hCGRP-(8-37) reduced both responses induced by acetic acid. CGRP mimicked the effects of acetic acid. RP-67580 abolished CGRP-induced gastric emptying inhibition, whereas SR-48968 only diminished visceral pain. GR-73632 reduced gastric emptying, and GR-64349 increased abdominal response. In inflammation, neurokinin receptors (NK1 and NK2) mediate the gastric emptying inhibition and visceral pain, respectively. These responses involve a release of CGRP.

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Calcitonin gene-related peptide in viscerosensitive response to colorectal distension in rats

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.1997.273.1.g191 ◽

1997 ◽

Vol 273 (1) ◽

pp. G191-G196 ◽

Cited By ~ 15

Author(s):

V. Plourde ◽

S. St-Pierre ◽

R. Quirion

Keyword(s):

Acetic Acid ◽

Visceral Pain ◽

Intrathecal Administration ◽

Calcitonin Gene Related Peptide ◽

Visceral Hyperalgesia ◽

Afferent Pathways ◽

Colorectal Distension ◽

Related Peptide ◽

Balloon Distension ◽

Calcitonin Gene

The role of calcitonin gene-related peptide (CGRP) on colorectal distension-induced visceral pain was investigated in conscious rats. Intracolonic administration of acetic acid (0.6%) resulted in a significantly increased number of abdominal contractions in response to colorectal balloon distension from 5.8 +/- 1.2 in controls to 16.6 +/- 1.0 in acetic acid-treated animals (P < 0.05), evidencing sensitization of visceral afferent pathways and subsequently visceral hyperalgesia. This sensitization phenomenon was not observed in animals previously treated with systemic capsaicin. Likewise, in animals not treated with capsaicin, use of an intravenous antagonist for CGRP [human CGRP-(8-37)], completely reversed the sensitizing effects of acetic acid. Furthermore, intravenous administration of CGRP dose dependently increased the number of abdominal contractions in response to colorectal distension from 3.0 +/- 1.1 (CGRP 250 ng) to 17.0 +/- 1.2 (CGRP 500 ng, P < 0.05), as previously observed in acetic acid-treated animals. Finally, intrathecal administration of hCGRP-(8–37) (mid-lumbar) also resulted in a total dose-dependent reversal of CGRP (500 ng) or acetic acid-induced visceral hypersensitivity. These results demonstrate that CGRP plays a major role in this model of visceral afferent nerve sensitization from gastrointestinal origin.

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Comparative effect of the prolyl endopeptidase inhibitors, benzyloxycarbonyl-prolyl-prolinal and benzyloxycarbonyl-methionyl-cyanopyrrolidine, on the acute exudative inflammation and visceral pain in mice

Biomeditsinskaya Khimiya ◽

10.18097/pbmc20206605423 ◽

2020 ◽

Vol 66 (5) ◽

pp. 423-426

Author(s):

E.A. Ivanova ◽

N.N. Zolotov ◽

T.A. Voronina

Keyword(s):

Acetic Acid ◽

Visceral Pain ◽

Prolyl Endopeptidase ◽

Comparative Effect ◽

Outbred Mice

A selective prolyl endopeptidase (PEP) inhibitor benzyloxycarbonyl-prolyl-prolinal (IC50 = 1,61±0,12 nmol/l) and a nonselective PEP inhibitor benzyloxycarbonyl-methionyl-cyanopyrrolidine (IC50 = 2,01±0,14 nmol/l) exhibit a comparable antiexudative effect at single doses of 2 mg/kg and 5 mg/kg (intraperitoneally) in outbred mice with peritonitis induced by 1% acetic acid. However, only benzyloxycarbonyl-methionyl-cyanopyrrolidine at a dose of 5 mg/kg reduces acetic acid induced pain in animals.

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Gabapentin Markedly Reduces Acetic Acid–induced Visceral Nociception

Anesthesiology ◽

10.1097/00000542-200303000-00023 ◽

2003 ◽

Vol 98 (3) ◽

pp. 729-733 ◽

Cited By ~ 89

Author(s):

Yi Feng ◽

Minglei Cui ◽

William D. Willis

Keyword(s):

Amino Acids ◽

Spinal Cord ◽

Acetic Acid ◽

Amino Acid ◽

Intraperitoneal Injection ◽

Visceral Pain ◽

Antinociceptive Effect ◽

Intraperitoneal Administration ◽

Amino Acid Release ◽

Acid Release

Background Gabapentin has recently been used clinically as an antihyperalgesic agent to treat certain neuropathic pain states. The aim of this study is to test whether gabapentin is able to inhibit responses to peritoneal irritation-induced visceral pain and to examine the effect of gabapentin on spinal cord amino acid release. Methods The acetic acid-induced writhing assay was used in rats to determine the degree of antinociception. The rats received an intraperitoneal injection of acetic acid 40 min after intraperitoneal administration of vehicle or gabapentin (50, 100, or 200 mg/kg). Cerebrospinal fluid dialysate was collected by microdialysis from the spinal subarachnoid space in anesthetized rats. Acetic acid-induced release of amino acids into the dialysate, including glutamate, aspartate, serine, glutamine, and glycine, following intraperitoneal injection of acetic acid was evaluated by measurements of changes in the concentrations of these amino acids. The effects of pretreatment with saline or gabapentin (100 mg/kg intraperitoneal) on amino acid release were compared. Results Gabapentin reduced writhing responses in a dose-related fashion. Dialysate concentrations of glutamate, aspartate, and serine increased significantly following intraperitoneal injection of acetic acid, while glutamine and glycine concentrations were not increased significantly. When compared to saline-treated rats, animals pretreated with 100 mg/kg gabapentin showed suppression of the acetic acid-induced increases in glutamate, aspartate, and serine concentrations. Conclusions These data demonstrate that gabapentin effectively inhibits acetic acid-induced nociception, and the antinociceptive effect of gabapentin correlates with the suppression of noxious-evoked release of excitatory amino acids in the spinal cord.

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Changes in saccharin preference behavior as a primary outcome to evaluate pain and analgesia in acetic acid-induced visceral pain in mice

Journal of Pain Research ◽

10.2147/jpr.s91230 ◽

2015 ◽

pp. 663 ◽

Cited By ~ 1

Author(s):

Enrique Portillo-Salido ◽

Beatriz De la Puente ◽

Elizabeth Romero-Alejo ◽

José Miguel Vela ◽

Manuel Merlos ◽

...

Keyword(s):

Acetic Acid ◽

Primary Outcome ◽

Visceral Pain ◽

Saccharin Preference ◽

Preference Behavior

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Increased visceral sensitivity to capsaicin after DSS-induced colitis in mice: spinal cord c-Fos expression and behavior

AJP Gastrointestinal and Liver Physiology ◽

10.1152/ajpgi.00114.2007 ◽

2007 ◽

Vol 293 (4) ◽

pp. G749-G757 ◽

Cited By ~ 46

Author(s):

Niels Eijkelkamp ◽

Annemieke Kavelaars ◽

Sigrid Elsenbruch ◽

Manfred Schedlowski ◽

Gerald Holtmann ◽

...

Keyword(s):

Spinal Cord ◽

Pain Perception ◽

Visceral Pain ◽

Activity Index ◽

Behavioral Responses ◽

Disease Activity Index ◽

Sensory Function ◽

Visceral Hyperalgesia ◽

Dss Colitis ◽

Fos Expression

During acute and chronic inflammation visceral pain perception is altered. Conflicting data exist, however, on visceral pain perception in the postinflammatory phase. The aim of the present study was to investigate whether visceral pain perception is altered after resolution of dextran sodium sulfate (DSS)-induced inflammation of the colon. Visceral sensory function in mice was assessed by monitoring behavioral responses to intracolonic capsaicin instillation. Two hours later the number of c-Fos-positive neurons in lamina I/II and X of spinal cord segments T12/13–S1 was determined as a measure of neuronal activation. DSS colitis was induced by adding 1% of DSS to the drinking water. The course of DSS-induced colitis was assessed by determining the disease activity index score. Animals developed a transient colitis and had recovered at day 49. At this time point, cytokine levels and colon length were similar to control animals. Importantly, after resolution of DSS-induced colitis the behavioral response to intracolonic capsaicin was increased compared with control mice. Moreover, capsaicin-induced spinal cord neuronal c-Fos expression was significantly increased. Interestingly, after colitis animals also exhibited referred somatic hyperalgesia as measured with von Frey hairs on the abdominal wall. We conclude that postinflammatory visceral hyperalgesia occurs after resolution of DSS-induced colitis and that capsaicin-induced behavioral responses and spinal cord neuronal c-Fos activation are effective readouts for determination of visceral pain perception.

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Comparison of analgesic activities of aconitine in different mice pain models

PLoS ONE ◽

10.1371/journal.pone.0249276 ◽

2021 ◽

Vol 16 (4) ◽

pp. e0249276

Author(s):

Jianhua Deng ◽

Jiada Han ◽

Jiahao Chen ◽

Yanmin Zhang ◽

Qiuju Huang ◽

...

Keyword(s):

Acetic Acid ◽

Visceral Pain ◽

Thermal Stimulus ◽

Diterpenoid Alkaloids ◽

Hot Plate ◽

Pain Model ◽

Analgesic Effects ◽

Pain Models ◽

Nociceptive Responses ◽

Analgesic Activities

Aconitine (AC) is the primary bioactive and secondary metabolite alkaloidin of Aconitum species which is accounted for more than 60% of the total diester-diterpenoid alkaloids in Aconite. To evaluate the analgesic effects of AC, 4 different pain models including hot plate assay, acetic acid writhing assay, formalin and CFA induced pain models were adopted in this study. In hot plate experiment, AC treatment at concentration of 0.3 mg/kg and 0.9 mg/kg improved the pain thresholds of mice similar to the positive drug aspirin at the concentration of 200 mg/kg (17.12% and 20.27% VS 19.21%). In acetic acid writhing experiment, AC significantly reduced the number of mice writhing events caused by acetic acid, and the inhibition rates were 68% and 76%. These results demonstrated that AC treatment revealed significant analgesic effects in both acute thermal stimulus pain model and chemically-induced visceral pain model. The biphasic nociceptive responses induced by formalin were significantly inhibited after AC treatment for 1h or 2h. The inhibition rates were 33.23% and 20.25% of AC treatment for 1h at 0.3 mg/kg and 0.9 mg/kg in phase I. In phase II, the inhibition rates of AC and aspirin were 36.08%, 32.48% and 48.82% respectively, which means AC showed similar analgesic effect to non-steroidal anti-inflammatory compounds. In the chronic CFA-induced nociception model, AC treatment also improved mice pain threshold to 131.33% at 0.3 mg/kg, which was similar to aspirin group (152.03%). Above all, our results verified that AC had obviously analgesic effects in different mice pain models.

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Afferent Fibers of the Hypogastric Nerves Are Involved in the Facilitating Effects of Chemical Bladder Irritation in Rats

Journal of Neurophysiology ◽

10.1152/jn.2001.86.5.2276 ◽

2001 ◽

Vol 86 (5) ◽

pp. 2276-2284 ◽

Cited By ~ 49

Author(s):

Takahiko Mitsui ◽

Hidehiro Kakizaki ◽

Shinobu Matsuura ◽

Kaname Ameda ◽

Mitsuhiro Yoshioka ◽

...

Keyword(s):

Spinal Cord ◽

Acetic Acid ◽

Marked Decrease ◽

Lumbar Spinal Cord ◽

Urinary Frequency ◽

Acid Infusion ◽

Afferent Fibers ◽

Fos Expression ◽

Lumbar Spinal

To evaluate the role of bladder afferent fibers in the hypogastric nerves (HGN) in modulation of the micturition reflex induced by chemical bladder irritation, voiding behavior, continuous cystometry, and spinal c-fos expression following intravesical acetic acid instillation were investigated in rats with or without HGN transection. Voiding behavior and continuous cystometry were examined in unanesthetized conscious rats. Following chemical bladder irritation, a significant increase in urinary frequency associated with a marked decrease in the voided volume per micturition, was noted in control rats with the intact HGN, but not in HGN-transected rats. Continuous infusion of acetic acid in control rats elicited irritative bladder responses characterized by a marked decrease in the intercontraction interval and a marked increase in maximal vesical pressure, both of which were absent in capsaicin-desensitized rats. HGN transection prevented the decrease in the intercontraction interval but not an increase in maximal vesical pressure following chemical bladder irritation. Compared with saline infusion, acetic acid infusion caused a significant increase in c-fos expression at L1 and L6 of the spinal cord, and HGN transection significantly reduced c-fos expression in the dorsal horn of the spinal cord at L1 but not at L6. These results suggest that capsaicin-sensitive bladder afferent fibers in the HGN, which travel through the rostral lumbar spinal cord, have a role in urinary frequency caused by chemical bladder irritation.

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