The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model

Stepanović-Petrović, Radica; Tomić, Maja; Vučković, Sonja; Paranos, Sonja; Ugresic, N.; Prostran, Milica; Milovanović, Srđan; Bošković, Bogdan

doi:10.1213/ane.0b013e318172b993

Cited by 42 publications

(33 citation statements)

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“…Both pregabaline and gabapentine are central analgesics [39]. Gabapentinoids inhibited visceral hypersensitivity in the experimental animals, as well as irritable bowel syndrome in humans [41]. Smalls doses of gabapentine administered with morphine inhibit i.p.…”

Section: Other Types Of Calcium Channel Blockers Used In the Treatmenmentioning

confidence: 99%

Voltage-Gated Calcium Channel Antagonists: Potential Analgesics for Jejunal Pains

Feliks¹,

Wrońska²

2017

Pain Relief - From Analgesics to Alternative Therapies

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The significant role of voltage-gated calcium channel (VGCC) L-type antagonists used concomitantly with opioids in attenuation of clinical pain has been confirmed. The aim of this study is to evaluate the comparable effect of intracerebroventricularly (i.c.v.) administered diltiazem, nifedipine and/or verapamil -specific antagonists of VGCCsin the dose of 1.0 and 2.0 mg in toto on behavioral signs, clinical symptoms, rumen motor activity and biochemical (plasma cortisol and catecholamine-CA) parameters in sheep that have undergone experimental duodenal distension (DD) and to determine whether voltage-gated calcium channel inhibitors (VGCCIs) exert any anti-nociceptive effects under these conditions. The study was carried out using 24 mature, behind reproductive season crossbred ewes, each weighing 32-42 kg. DD was managed by inclusion and the distension of stretching balloon (having 40 mL of water 39°C temperature-DD40). After 5 min of DD40, the signs were observed: an important augmentation of behavioral nociceptive signs, particularly looking around, defecation, head movement, stretching, grinding, lying down, tachycardia, hyperventilation, inhibition of ruminal contractions (70% approximately, during 15 min) and an increase in plasma catecholamine concentration (over sevenfold increase of epinephrine (E): from 0.24 ± 0.12 in control to 2.98 ± 0.21 mM L −1 during 2 h following DD, 2-times norepinephrine (NE): from 1.29 ± 0.23 in control to 2.51 ± 0.30 mM L −1 and 124% increase of dopamine (DA): from 0.94 ± 0.02 in control to 2.10 ± 0.35 mM L −1 ). VGCCI infusion administered 10 min before duodenal distension diminished severity of jejunal nociceptive reactions, for instance, behavioral symptoms, cardiac acceleration, increase in the number of respiration, inhibition of the reticulum and rumen hypomotility, and effortlessly abolished the increasing presence of plasma cortisol and biogenic amines (CA) release. We suggest that the increase and insistence of visceral hyperalgesia stimulate the flow of Ca 2+ ion flow, provoking neurohormones/neuromediators liberatione and cytoplasmic membrane responsiveness modulation. This result confirmed analgesic effects of VGCCIs L-and/or R-type (nimodipine, lercanidipine, SNX-482) obtained by other authors and also suggests that these channels play a crucial role in the modulation of acute visceral hyperalgesia in sheep and may be a therapeutic target for new drugs.

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Section: Other Types Of Calcium Channel Blockers Used In the Treatmenmentioning

confidence: 99%

Voltage-Gated Calcium Channel Antagonists: Potential Analgesics for Jejunal Pains

Feliks¹,

Wrońska²

2017

Pain Relief - From Analgesics to Alternative Therapies

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“…The writhing reflex is characterized by the presence of abdominal muscle contractions associated with inward outstretching of the hind limbs, a hind paw reflex, or whole body extension. 7,9,14,17,20 The number of writhing reflexes, a measure of visceral pain, were recorded for a 30-min period. 20 Drugs and experimental protocol…”

Section: Acetic Acid-induced Writhingmentioning

confidence: 99%

“…[4][5][6] Like most anticonvulsants, gabapentinoids have also been found to have an antinociceptive effect in visceral pain. 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.…”

mentioning

confidence: 99%

“…12 The acetic acid-induced writhing response in rodents is probably the best model of visceral pain, and it is considered to predict human response to pain. 7,13 Consequently, this model is widely used as a test to evaluate and compare efficacy of new drugs in visceral pain treatment. 7,9,[13][14][15][16][17][18] The writhing responses reflect peritoneovisceral pain, because acetic acid directly activates both visceral and somatic nociceptors that innervate the peritoneum.…”

mentioning

confidence: 99%

“…7,13 Consequently, this model is widely used as a test to evaluate and compare efficacy of new drugs in visceral pain treatment. 7,9,[13][14][15][16][17][18] The writhing responses reflect peritoneovisceral pain, because acetic acid directly activates both visceral and somatic nociceptors that innervate the peritoneum. This model also induces inflammation in the subcutaneous and muscular layers of the abdominal wall as well as in the subdiaphragmatic visceral organs.…”

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confidence: 99%

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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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Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test

Zúñiga-Romero

Ponce-Chávez

Gauthereau-Torres

et al. 2014

Drug Development Research

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Preclinical Research The present study was designed to evaluate the possible antinociceptive interaction between diacerhein and some antiepileptic drugs (carbamazepine, topiramate and gabapentin) on formalin-induced nociception. Diacerhein, each of the antiepileptics or a fixed dose-ratio combination of these drugs was assessed after local peripheral and oral administration in rats. lsobolographic analyses were used to define the interaction between drugs. Diacerhein, antiepileptic drugs (carbamazepine, topiramate and gabapentin) or their combinations yielded a dose-dependent antinociceptive effect when administered by both routes. Theoretical ED30 values for the combination estimated from the isobolograms were obtained as follows: diacerhein-carbamazepine (85.99 ± 7.07 μg/paw; 56.53 ± 4.56 mg/kg po), diacerhein-topiramate (197.97 ± 22.90 μg/paw; 13.06 ± 2.44 mg/kg po) and diacerhein-gabapentin (96.87 ± 17.73 μg/paw; 17.90 ± 4.70 mg/kg p.o.) for the local peripheral and oral administration routes, respectively. These values were significantly higher than the experimentally obtained ED30 values: diacerhein-carbamazepine (49.33 ± 3.37 μg/paw; 35.49 ± 7.91 mg/kg po), diacerhein-topiramate (133.00 ± 39.10 μg/paw; 8.87 ± 1.46 mg/kg po) and diacerhein-gabapentin (70.98 ± 14.73 μg/paw; 10.95 ± 3.23 mg/kg po). The combinations produced their antinociceptive effects without motor impairment in the rotarod test indicating synergistic interactions with a good side effect profile.

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The Antinociceptive Effects of Anticonvulsants in a Mouse Visceral Pain Model

Abstract: These results indicate that oxcarbazepine, gabapentin, and topiramate are effective in the writhing model in mice, in a dose range, which is not related to motor impairment; topiramate is the most potent and the most tolerable drug.

Cited by 42 publications

References 28 publications

Voltage-Gated Calcium Channel Antagonists: Potential Analgesics for Jejunal Pains

Voltage-Gated Calcium Channel Antagonists: Potential Analgesics for Jejunal Pains

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

Combination of Diacerhein and Antiepileptic Drugs After Local Peripheral, and Oral Administration in the Rat Formalin Test

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