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

2015 ◽  
pp. 663 ◽  
Author(s):  
Enrique Portillo-Salido ◽  
Beatriz De la Puente ◽  
Elizabeth Romero-Alejo ◽  
José Miguel Vela ◽  
Manuel Merlos ◽  
...  
1997 ◽  
Vol 272 (1) ◽  
pp. G141-G146 ◽  
Author(s):  
V. Julia ◽  
L. Bueno

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.


1997 ◽  
Vol 273 (1) ◽  
pp. G191-G196 ◽  
Author(s):  
V. Plourde ◽  
S. St-Pierre ◽  
R. Quirion

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.


2020 ◽  
Vol 66 (5) ◽  
pp. 423-426
Author(s):  
E.A. Ivanova ◽  
N.N. Zolotov ◽  
T.A. Voronina

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.


2003 ◽  
Vol 98 (3) ◽  
pp. 729-733 ◽  
Author(s):  
Yi Feng ◽  
Minglei Cui ◽  
William D. Willis

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.


2000 ◽  
Vol 118 (4) ◽  
pp. A838
Author(s):  
Valerie Sinniger ◽  
Christophe Lamy ◽  
Jacques Fournet ◽  
Marie-Odile Christen ◽  
Bruno L. Bonaz

PLoS ONE ◽  
2021 ◽  
Vol 16 (4) ◽  
pp. e0249276
Author(s):  
Jianhua Deng ◽  
Jiada Han ◽  
Jiahao Chen ◽  
Yanmin Zhang ◽  
Qiuju Huang ◽  
...  

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.


Pain ◽  
2004 ◽  
Vol 110 (3) ◽  
pp. 738-750 ◽  
Author(s):  
Valérie Sinniger ◽  
Christophe Porcher ◽  
Patrick Mouchet ◽  
Aurélie Juhem ◽  
Bruno Bonaz

2015 ◽  
Vol 14 (3) ◽  
pp. 282-290 ◽  
Author(s):  
Shaojun Ma ◽  
Ying Zhang ◽  
Xiaojiang Li ◽  
He Zhang ◽  
Yingjie Jia

2020 ◽  
Vol 66 (1) ◽  
pp. 77-82
Author(s):  
E.A. Ivanova ◽  
N.N. Zolotov ◽  
V.F. Pozdnev ◽  
T.A. Voronina

Cyanopyrrolidine derivatives benzyloxycarbonyl-methionyl-cyanopyrrolidine (ZMetPrdN), benzyloxycarbonylphenylalanyl- cyanopyrrolidine (ZPhePrdN), tert-butyl-hydroxycarbonyl-glycyl-cyanopyrrolidine (BocGlyPrdN), tert-butyl-hydroxycarbonyl-methionyl-cyanopyrrolidine (BocMetPrdN) are inhibitors of prolylendopeptidase (PREP; EC 3.4.21.26) with an IC50 of 2 nM to 12 nM. ZMetPrdN, ZPhePrdN and BocMetPrdN additionally inhibited dipeptidyl peptidase IV (DPP-4; EC 3.4.14.5) with an IC50 of 1100 nM to 3200 nM. All the compounds have antinociceptive properties in the acetic acid writhing test in mice. But only cyanopyrrolidine derivatives with aromatic substituents decrease exudative inflammation. The cyanopyrrolidine derivatives also increase PREP activity and compensatorily reduce DPP-4 activity in the serum of mice three hours after the induction of inflammation. Thus, cyanopyrrolidine derivatives exhibit antinociceptive and antiexudative properties in part via their effect on PREP.


Neuroscience ◽  
2010 ◽  
Vol 165 (4) ◽  
pp. 1429-1438 ◽  
Author(s):  
X. Huang ◽  
J. Yang ◽  
J.K. Chang ◽  
N.J. Dun

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