Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Diop, Laurent; Raymond, Frédéric; Fargeau, H.; Petoux, Francine; Chovet, Maria; Doherty, Annette M.

doi:10.1124/jpet.302.3.1013

Cited by 88 publications

(78 citation statements)

References 36 publications

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“…The presence of somatic hypersensitivity is a new finding as previous studies using TNBS colitis in rats have only evaluated colonic hypersensitivity [20][21][22][23][24]. There have been several previous studies that have used other visceral cavities (i.e.…”

Section: Discussionmentioning

confidence: 99%

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

et al. 2007

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Inflammation of visceral structures in rats has been shown to produce visceral/somatic hyperalgesia. Our objectives were to determine if trinitrobenzene sulfonic acid (TNBS) induced colitis in rats leads to visceral/somatic hypersensitivity. Male Sprague-Dawley rats (200g-250g) were treated with 20 mg of TNBS in 50% ethanol (n=40) or an equivalent volume of ethanol (n=40) or saline (n=25) via the colon. Colonic distension, Von-Frey, Hargreaves, and tail reflex test were used to evaluate for visceral, mechanical, and thermal sensitivity. The rats demonstrated visceral hypersensitivity at 2-28 days following TNBS (p<0.0001). The ethanol treated rats also demonstrated visceral hypersensitivity that resolved after day 14. TNBS treated rats demonstrated somatic hypersensitivity at days 14-28 (p<0.0001) in response to somatic stimuli of the hind-paw. TNBS colitis is associated with visceral and somatic hypersensitivity in areas of somatotopic overlap. This model of colitis should allow further investigation into the mechanisms of visceral and somatic hypersensitivity.

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Section: Discussionmentioning

confidence: 99%

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

et al. 2007

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“…To measure the pain threshold in response to colonic distension, we used behavioral signs of pain as an endpoint in the TNBS-induced visceral hypersensitivity model. This endpoint has been previously used and defined as a pain response in other studies because morphine showed potent efficacy on TNBS-induced visceral hypersensitivity (11). Using this endpoint, we demonstrated that PF-03550096 significantly inhibited TNBS-induced visceral hypersensitivity; this effect was reversed by the CB 2 -selective antagonist SR144528.…”

Section: Discussionmentioning

confidence: 74%

“…Sham animals underwent the same surgery but were not administered TNBS. Seven days after surgery, colonic pain threshold was measured as previously reported (11,12). Animals were fasted for 16 -18 h and then placed individually into polypropylene cages.…”

Section: Visceral Hypersensitivity Modelmentioning

confidence: 99%

Pharmacological Evaluation of a Novel Cannabinoid 2 (CB2) Ligand, PF-03550096, In Vitro and In Vivo by Using a Rat Model of Visceral Hypersensitivity

et al. 2008

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Abstract. Previous studies have shown that cannabinoid 2 (CB 2 )-receptor agonists might have analgesic effects on visceral hypersensitivity. To extend these results, we have determined the pharmacological characteristics of a newly designed, in vitro and in vivo. PF-03550096 showed high affinity to human (K i = 7.9 ± 1.7 nM) and rat CB 2 receptors (K i = 47 ± 5.6 nM). In a cell-based functional assay, PF-03550096 behaved as a full agonist and showed high selectivity for human CB 2 receptors. Orally administered PF-03550096 (3, 10 mg / kg) inhibited the 2,4,6-trinitrobenzene sulfonic acid (TNBS)-induced decrease in colonic pain threshold with statistical significance. The inhibitory effect of PF-03550096 (10 mg / kg) was significantly reversed by a selective CB 2 antagonist, N-(1S)-endo-1,3,3-trimethylbicyclo[2.2.1]heptan-2-yl-5-(4-chloro-3-methylphenyl)-1(4-methylbenzyl)-pyrazole-3-carboxamide (SR144528), while SR144528 itself did not modify colonic pain threshold. These results indicate that PF-03550096 is a potent CB 2 agonist and possesses efficacy in a rat model of visceral hypersensitivity.

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“…The maximum doses of gabapentin and morphine selected were 200 and 5 mgÁkg -1 , respectively, based on similar studies, 4,9,14,16 while the maximum dose for pregabalin, which was novel in this model, was presumed to be 200 mgÁkg -1 . 8 The dose used for the dose-response data was the maximum dose and simple divisions ( , …) of that dose. Dilutions were made in normal saline so that a volume of 1/100 of mouse body weight would be injected.…”

Section: Acetic Acid-induced Writhingmentioning

confidence: 99%

“…7 Previous reports have shown that pregabalin inhibits trinitrobenzene sulfonic acid-induced allodynia in rats, and gabapentin inhibits acetic acid-induced irritation in rats. 8,9 Both pregabalin and gabapentin are recognized to reduce pain behaviour in colorectal distension and stress-induced visceral pain in rats. 10,11 Visceral pain still constitutes a large portion of clinically treated pain.…”

mentioning

confidence: 99%

Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain

Meymandi

Keyhanfar

2012

Can J Anesth/J Can Anesth

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Purpose Pregabalin is probably more effective than prototype gabapentin in different kinds of pain treatments. This study was performed to compare the potency of gabapentin, pregabalin, and morphine in a well-established model of visceral pain. Methods The number of abdominal contractions was counted for 30 min in adult male mice that received different doses of pregabalin, gabapentin, morphine, or placebo intraperitoneally 30 min before receiving 0.6% acetic acid 10 mLÁkg -1 .The antinociceptive effect of each drug dose was determined as a percentage of the reduction in the number of acetic acid-induced writhes. The effective doses, for 20%, 50%, and 80% response (ED 20 , ED 50 , and ED 80 , respectively), of each drug were calculated using least squares linear regression analysis, and then dose-response curves were compared. Results Pregabalin, gabapentin, and morphine produced a linear dose-dependent antinociceptive effect (coefficient of determination [r 2 ] [ 0.9). No difference was observed between slopes of dose-response curves. The ED 50 estimates (95% confidence interval) for pregabalin, gabapentin, and morphine were 17.1 (12.9 to 22.1) mgÁkg -1 , 87.1 (45.8 to 129.8) mgÁkg -1 , and 0.2 (0.1 to 0.3) mgÁkg -1 , respectively. Conclusion In this animal model of visceral pain, all three drugs exhibited parallel dose-response curves. Pregabalin had five times the potency of gabapentin and 1/85 th the potency of morphine. Similar potency ratios may apply in clinical practice. Despite some limitations of animal studies, this model could be useful for comparing new analgesics in visceral pain treatment.Résumé ObjectifLa pre´gabaline est probablement plus efficace que son prototype, la gabapentine, dans divers traitements contre la douleur. Cette e´tude a e´te´re´alise´e pour comparer la puissance de la gabapentine, de la pre´gabaline et de la morphine dans un mode`le bien e´tabli de douleur visce´rale. Méthode Le nombre de contractions abdominales a e´teć ompte´pendant 30 min chez des souris maˆles adultes recevant diffe´rentes doses de pre´gabaline, de gabapentine, de morphine ou de placebo par voie intrape´ritone´ale 30 min avant 0,6 % d'acide ace´tique (10 mLÁkg -1 ). L'effet antinociceptif de chaque dose de me´dicament a e´ted e´termine´en tant que pourcentage de re´duction du nombre de contorsions induites par l'acide ace´tique. Les doses efficaces (DE) 20 %, 50 % et 80 % (DE 20 , DE 50 et DE 80 ) de chaque me´dicament ont e´te´calcule´es a`l'aide de l'analyse de re´gression line´aire des moindres carre´s et les courbes de dose-re´ponse ont ensuite e´te´compare´es. Résultats La pre´gabaline, la gabapentine et la morphine ont produit un effet antinociceptif de´pendant line´airement de la dose (coefficient de de´termination [r 2 ] [ 0,9).

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Pregabalin (CI-1008) Inhibits the Trinitrobenzene Sulfonic Acid-Induced Chronic Colonic Allodynia in the Rat

Cited by 88 publications

References 36 publications

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

Visceral and Somatic Hypersensitivity in TNBS-Induced Colitis in Rats

Pharmacological Evaluation of a Novel Cannabinoid 2 (CB2) Ligand, PF-03550096, In Vitro and In Vivo by Using a Rat Model of Visceral Hypersensitivity

Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain

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