Skip to main content
Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie 1/2013

01.01.2013 | Reports of Original Investigations

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

verfasst von: Manzumeh Shamsi Meymandi, PharmD, Fariborz Keyhanfar, PhD

Erschienen in: Canadian Journal of Anesthesia/Journal canadien d'anesthésie | Ausgabe 1/2013

Einloggen, um Zugang zu erhalten

Abstract

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 mL·kg−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 (ED20, ED50, and ED80, 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 [r2] > 0.9). No difference was observed between slopes of dose-response curves. The ED50 estimates (95% confidence interval) for pregabalin, gabapentin, and morphine were 17.1 (12.9 to 22.1) mg·kg−1, 87.1 (45.8 to 129.8) mg·kg−1, and 0.2 (0.1 to 0.3) mg·kg−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 1/85th 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.
Fußnoten
1
Motulsky H, Christopoulos A. Fitting Models to Biological Data using Linear and Nonlinear Regression. A Practical Guide to Curve Fitting. San Diego, CA: Graphpad Software Inc., 2003, www.​graphpad.​com.
 
Literatur
1.
Zurück zum Zitat Field MJ, Cox PJ, Stott E, et al. Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A 2006; 103: 17537-42.PubMedCrossRef Field MJ, Cox PJ, Stott E, et al. Identification of the alpha2-delta-1 subunit of voltage-dependent calcium channels as a molecular target for pain mediating the analgesic actions of pregabalin. Proc Natl Acad Sci U S A 2006; 103: 17537-42.PubMedCrossRef
2.
Zurück zum Zitat Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain 2010; 150: 573-81.PubMedCrossRef Finnerup NB, Sindrup SH, Jensen TS. The evidence for pharmacological treatment of neuropathic pain. Pain 2010; 150: 573-81.PubMedCrossRef
3.
Zurück zum Zitat Tzellos TG, Toulis KA, Goulis DG, et al. Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis. J Clin Pharm Ther 2010; 35: 639-56.PubMedCrossRef Tzellos TG, Toulis KA, Goulis DG, et al. Gabapentin and pregabalin in the treatment of fibromyalgia: a systematic review and a meta-analysis. J Clin Pharm Ther 2010; 35: 639-56.PubMedCrossRef
4.
Zurück zum Zitat Meymandi MS, Sepehri G, Mobasher M. Gabapentin enhances the analgesic response to morphine in acute model of pain in male rats. Pharmacol Biochem Behav 2006; 85: 185-9.PubMedCrossRef Meymandi MS, Sepehri G, Mobasher M. Gabapentin enhances the analgesic response to morphine in acute model of pain in male rats. Pharmacol Biochem Behav 2006; 85: 185-9.PubMedCrossRef
5.
Zurück zum Zitat Luszczki JJ, Kolacz A, Wojda E, Czuczwar M, Przesmycki K, Czuczwar SJl. Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: an isobolographic analysis. Pharmacol Rep 2009; 61: 459-67.PubMed Luszczki JJ, Kolacz A, Wojda E, Czuczwar M, Przesmycki K, Czuczwar SJl. Synergistic interaction of gabapentin with tiagabine in the hot-plate test in mice: an isobolographic analysis. Pharmacol Rep 2009; 61: 459-67.PubMed
6.
Zurück zum Zitat Luszczki JJ. Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hot-plate test in mice. Pharmacol Rep 2010; 62: 942-8.PubMed Luszczki JJ. Dose-response relationship analysis of pregabalin doses and their antinociceptive effects in hot-plate test in mice. Pharmacol Rep 2010; 62: 942-8.PubMed
7.
Zurück zum Zitat Stepanovic-Petrovic RM, Tomic MA, Vuckovic SM, et al. The antinociceptive effects of anticonvulsants in a mouse visceral pain model. Anesth Analg 2008; 106: 1897-903.PubMedCrossRef Stepanovic-Petrovic RM, Tomic MA, Vuckovic SM, et al. The antinociceptive effects of anticonvulsants in a mouse visceral pain model. Anesth Analg 2008; 106: 1897-903.PubMedCrossRef
8.
Zurück zum Zitat Diop L, Raymond F, Fargeau H, Petoux F, Chovet M, Doherty AM. Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat. J Pharmacol Exp Ther 2002; 302: 1013-22.PubMedCrossRef Diop L, Raymond F, Fargeau H, Petoux F, Chovet M, Doherty AM. Pregabalin (CI-1008) inhibits the trinitrobenzene sulfonic acid-induced chronic colonic allodynia in the rat. J Pharmacol Exp Ther 2002; 302: 1013-22.PubMedCrossRef
9.
Zurück zum Zitat Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology 2003; 98: 729-33.PubMedCrossRef Feng Y, Cui M, Willis WD. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology 2003; 98: 729-33.PubMedCrossRef
10.
Zurück zum Zitat O’Mahony SM, Coelho AM, Fitzgerald P, et al. The effects of gabapentin in two animal models of co-morbid anxiety and visceral hypersensitivity. Eur J Pharmacol 2011; 667: 169-74.CrossRef O’Mahony SM, Coelho AM, Fitzgerald P, et al. The effects of gabapentin in two animal models of co-morbid anxiety and visceral hypersensitivity. Eur J Pharmacol 2011; 667: 169-74.CrossRef
11.
Zurück zum Zitat Ravnefjord A, Brusberg M, Larsson H, Lindstrom E, Martinez V. Effects of pregabalin on visceral pain responses and colonic compliance in rats. Br J Pharmacol 2008; 155: 407-16.PubMedCrossRef Ravnefjord A, Brusberg M, Larsson H, Lindstrom E, Martinez V. Effects of pregabalin on visceral pain responses and colonic compliance in rats. Br J Pharmacol 2008; 155: 407-16.PubMedCrossRef
13.
Zurück zum Zitat Le Bars D, Gozariu M, Cadden SW. Critical analysis of animal models of acute pain. II (French). Ann Fr Anesth Reanim 2001; 20: 452-70.PubMedCrossRef Le Bars D, Gozariu M, Cadden SW. Critical analysis of animal models of acute pain. II (French). Ann Fr Anesth Reanim 2001; 20: 452-70.PubMedCrossRef
14.
Zurück zum Zitat Meymandi MS, Sepehri G. Gabapentin action and interaction on the antinociceptive effect of morphine on visceral pain in mice. Eur J Anaesthesiol 2008; 25: 129-34.PubMedCrossRef Meymandi MS, Sepehri G. Gabapentin action and interaction on the antinociceptive effect of morphine on visceral pain in mice. Eur J Anaesthesiol 2008; 25: 129-34.PubMedCrossRef
15.
Zurück zum Zitat Reichert JA, Daughters RS, Rivard R, Simone DA. Peripheral and preemptive opioid antinociception in a mouse visceral pain model. Pain 2001; 89: 221-7.PubMedCrossRef Reichert JA, Daughters RS, Rivard R, Simone DA. Peripheral and preemptive opioid antinociception in a mouse visceral pain model. Pain 2001; 89: 221-7.PubMedCrossRef
16.
Zurück zum Zitat Romero A, Miranda HF, Puig MM. Analysis of the opioid-opioid combinations according to the nociceptive stimulus in mice. Pharmacol Res 2010; 61: 511-8.PubMedCrossRef Romero A, Miranda HF, Puig MM. Analysis of the opioid-opioid combinations according to the nociceptive stimulus in mice. Pharmacol Res 2010; 61: 511-8.PubMedCrossRef
17.
Zurück zum Zitat Satyanarayana PS, Jain NK, Singh A, Kulkarni SK. Isobolographic analysis of interaction between cyclooxygenase inhibitors and tramadol in acetic acid-induced writhing in mice. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 641-9.PubMedCrossRef Satyanarayana PS, Jain NK, Singh A, Kulkarni SK. Isobolographic analysis of interaction between cyclooxygenase inhibitors and tramadol in acetic acid-induced writhing in mice. Prog Neuropsychopharmacol Biol Psychiatry 2004; 28: 641-9.PubMedCrossRef
18.
Zurück zum Zitat Stevenson GW, Cormier J, Mercer H, et al. Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice. Life Sci 2009; 85: 309-15.PubMedCrossRef Stevenson GW, Cormier J, Mercer H, et al. Targeting pain-depressed behaviors in preclinical assays of pain and analgesia: drug effects on acetic acid-depressed locomotor activity in ICR mice. Life Sci 2009; 85: 309-15.PubMedCrossRef
19.
Zurück zum Zitat Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev 2001; 53: 597-652.PubMed Le Bars D, Gozariu M, Cadden SW. Animal models of nociception. Pharmacol Rev 2001; 53: 597-652.PubMed
20.
Zurück zum Zitat Mogil JS, Kest B, Sadowski B, Belknap JK. Differential genetic mediation of sensitivity to morphine in genetic models of opiate antinociception: influence of nociceptive assay. J Pharmacol Exp Ther 1996; 276: 532-44.PubMed Mogil JS, Kest B, Sadowski B, Belknap JK. Differential genetic mediation of sensitivity to morphine in genetic models of opiate antinociception: influence of nociceptive assay. J Pharmacol Exp Ther 1996; 276: 532-44.PubMed
21.
Zurück zum Zitat Hurley RW, Chatterjea D, Rose Feng M, Taylor CP, Hammond DL. Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia. Anesthesiology 2002; 97: 1263-73.PubMedCrossRef Hurley RW, Chatterjea D, Rose Feng M, Taylor CP, Hammond DL. Gabapentin and pregabalin can interact synergistically with naproxen to produce antihyperalgesia. Anesthesiology 2002; 97: 1263-73.PubMedCrossRef
22.
Zurück zum Zitat Tanabe M, Ono K, Honda M, Ono H. Gabapentin and pregabalin ameliorate mechanical hypersensitivity after spinal cord injury in mice. Eur J Pharmacol 2009; 609: 65-8.PubMedCrossRef Tanabe M, Ono K, Honda M, Ono H. Gabapentin and pregabalin ameliorate mechanical hypersensitivity after spinal cord injury in mice. Eur J Pharmacol 2009; 609: 65-8.PubMedCrossRef
23.
Zurück zum Zitat Gale JD, Houghton LA. Alpha 2 delta (alpha(2)delta) ligands, gabapentin and pregabalin: what is the evidence for potential use of these ligands in irritable bowel syndrome. Front Pharmacol 2011; 2: 28.PubMedCrossRef Gale JD, Houghton LA. Alpha 2 delta (alpha(2)delta) ligands, gabapentin and pregabalin: what is the evidence for potential use of these ligands in irritable bowel syndrome. Front Pharmacol 2011; 2: 28.PubMedCrossRef
24.
Zurück zum Zitat Tzellos TG, Papazisis G, Amaniti E, Kouvelas D. Efficacy of pregabalin and gabapentin for neuropathic pain in spinal-cord injury: an evidence-based evaluation of the literature. Eur J Clin Pharmacol 2008; 64: 851-8.PubMedCrossRef Tzellos TG, Papazisis G, Amaniti E, Kouvelas D. Efficacy of pregabalin and gabapentin for neuropathic pain in spinal-cord injury: an evidence-based evaluation of the literature. Eur J Clin Pharmacol 2008; 64: 851-8.PubMedCrossRef
25.
Zurück zum Zitat Bian F, Li Z, Offord J, et al. Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. Brain Res 2006; 1075: 68-80.PubMedCrossRef Bian F, Li Z, Offord J, et al. Calcium channel alpha2-delta type 1 subunit is the major binding protein for pregabalin in neocortex, hippocampus, amygdala, and spinal cord: an ex vivo autoradiographic study in alpha2-delta type 1 genetically modified mice. Brain Res 2006; 1075: 68-80.PubMedCrossRef
26.
Zurück zum Zitat Dubinsky B, Gebre-Mariam S, Capetola RJ, Rosenthale ME. The antialgesic drugs: human therapeutic correlates of their potency in laboratory animal models of hyperalgesia. Agents Actions 1987; 20: 50-60.PubMedCrossRef Dubinsky B, Gebre-Mariam S, Capetola RJ, Rosenthale ME. The antialgesic drugs: human therapeutic correlates of their potency in laboratory animal models of hyperalgesia. Agents Actions 1987; 20: 50-60.PubMedCrossRef
27.
Zurück zum Zitat Collier HO, Dinneen LC, Johnson CA, Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother 1968; 32: 295-310.PubMedCrossRef Collier HO, Dinneen LC, Johnson CA, Schneider C. The abdominal constriction response and its suppression by analgesic drugs in the mouse. Br J Pharmacol Chemother 1968; 32: 295-310.PubMedCrossRef
28.
Zurück zum Zitat Houghton LA, Fell C, Whorwell PJ, Jones I, Sudworth DP, Gale JD. Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut 2007; 56: 1218-25.PubMedCrossRef Houghton LA, Fell C, Whorwell PJ, Jones I, Sudworth DP, Gale JD. Effect of a second-generation alpha2delta ligand (pregabalin) on visceral sensation in hypersensitive patients with irritable bowel syndrome. Gut 2007; 56: 1218-25.PubMedCrossRef
Metadaten
Titel
Relative potency of pregabalin, gabapentin, and morphine in a mouse model of visceral pain
verfasst von
Manzumeh Shamsi Meymandi, PharmD
Fariborz Keyhanfar, PhD
Publikationsdatum
01.01.2013
Verlag
Springer-Verlag
Erschienen in
Canadian Journal of Anesthesia/Journal canadien d'anesthésie / Ausgabe 1/2013
Print ISSN: 0832-610X
Elektronische ISSN: 1496-8975
DOI
https://doi.org/10.1007/s12630-012-9813-6

Weitere Artikel der Ausgabe 1/2013

Canadian Journal of Anesthesia/Journal canadien d'anesthésie 1/2013 Zur Ausgabe

Mehr Frauen im OP – weniger postoperative Komplikationen

21.05.2024 Allgemeine Chirurgie Nachrichten

Ein Frauenanteil von mindestens einem Drittel im ärztlichen Op.-Team war in einer großen retrospektiven Studie aus Kanada mit einer signifikanten Reduktion der postoperativen Morbidität assoziiert.

Delir bei kritisch Kranken – Antipsychotika versus Placebo

16.05.2024 Delir Nachrichten

Um die Langzeitfolgen eines Delirs bei kritisch Kranken zu mildern, wird vielerorts auf eine Akuttherapie mit Antipsychotika gesetzt. Eine US-amerikanische Forschungsgruppe äußert jetzt erhebliche Vorbehalte gegen dieses Vorgehen. Denn es gibt neue Daten zum Langzeiteffekt von Haloperidol bzw. Ziprasidon versus Placebo.

Eingreifen von Umstehenden rettet vor Erstickungstod

15.05.2024 Fremdkörperaspiration Nachrichten

Wer sich an einem Essensrest verschluckt und um Luft ringt, benötigt vor allem rasche Hilfe. Dass Umstehende nur in jedem zweiten Erstickungsnotfall bereit waren, diese zu leisten, ist das ernüchternde Ergebnis einer Beobachtungsstudie aus Japan. Doch es gibt auch eine gute Nachricht.

Darf man die Behandlung eines Neonazis ablehnen?

08.05.2024 Gesellschaft Nachrichten

In einer Leseranfrage in der Zeitschrift Journal of the American Academy of Dermatology möchte ein anonymer Dermatologe bzw. eine anonyme Dermatologin wissen, ob er oder sie einen Patienten behandeln muss, der eine rassistische Tätowierung trägt.

Update AINS

Bestellen Sie unseren Fach-Newsletter und bleiben Sie gut informiert.