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Gabapentin action and interaction on the antinociceptive effect of morphine on visceral pain in mice

Published online by Cambridge University Press:  01 February 2008

M.-S. Meymandi  and
G. Sepehri
M.-S. Meymandi*
Affiliation:
Kerman University of Medical Sciences, Kerman Neuroscience Research Center, Physiology and Pharmacology Department, Kerman, Iran
G. Sepehri
Affiliation:
Kerman University of Medical Sciences, Kerman Neuroscience Research Center, Physiology and Pharmacology Department, Kerman, Iran
*
Correspondence to: Manzumeh Shamsi Meymandi, Physiology and Pharmacology Department, Neuroscience Research Center, Kerman University of Medical Sciences, 22 Bahman Blvd., 76169-1411, Kerman, Iran. E-mail: manzume@yahoo.com; Tel: 98 341 3220081; Fax : 98 341 2111010
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Summary

Background and objective

Visceral pain is one of the most common forms of pain and for which new drugs would be welcome. The aim of this study was to investigate whether gabapentin inhibits induced abdominal contractions in mice and to examine the effect of its co-administration with morphine.

Methods

A total of 96 mice received acetic acid intraperitoneally after administration of saline or gabapentin (1, 5, 10, 50 and 100 mg kg−1) or morphine (0.25, 0.5, 1, 3 and 5 mg kg−1) or a combination of morphine and gabapentin. Other groups also received naloxone. The number of writhes were counted.

Results

Both gabapentin and morphine reduced writhing in a dose-dependent manner. The number of writhes was decreased significantly by gabapentin (50 and 100 mg kg−1) and morphine (0.5, 1, 3 and 5 mg kg−1) (P < 0.001). Also, the lowest dose of morphine 0.25 mg kg−1 when combined with low doses of gabapentin significantly decreased the number of writhes (P < 0.005). The combination of a low effective dose of gabapentin (50 mg kg−1) with a low dose of morphine decreased the writhing by 94% as compared to the controls. The antinociceptive effect of combined administration was not reversed by naloxone.

Conclusion

These data demonstrated the comparable efficacy of gabapentin with morphine in visceral pain. Also, the results showed that the combination of doses of gabapentin and morphine, which were ineffective alone, produced a significant analgesic effect in the writhing model of pain. This may be clinically important in the management of visceral pain.

Keywords

GABAPENTINMORPHINEPAIN, visceralPAIN MEASUREMENTMICE
Type
Original Article
Information
European Journal of Anaesthesiology , Volume 25 , Issue 2 , February 2008 , pp. 129 - 134
Copyright
Copyright © European Society of Anaesthesiology 2007

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References

1.Cervero, F, Laird, JM. Visceral pain. Lancet 1999; 353: 2145–2148.CrossRefGoogle ScholarPubMed
2.Way, WL, Field, HL, Schumacher, MA. Opioid analgesics and antagonists. In: Katzung, BG, ed. Basic and Clinical Pharmacology, 8th edn. USA: Lange Medical Books/McGraw-Hill Companies, 2001: 512–532.Google Scholar
3.Portenoy, RK. Tolerance to opioid analgesics: clinical aspects. Cancer Surv 1994; 21: 49–65.Google ScholarPubMed
4.Goa, KL, Sorkin, EM. Gabapentin. A review of its pharmacological properties and clinical potential in epilepsy. Drugs 1993; 46: 409–427.CrossRefGoogle ScholarPubMed
5.Rose, MA, Kam, PC. Gabapentin: pharmacology and its use in pain management. Anaesthesia 2002; 57: 451–462.CrossRefGoogle ScholarPubMed
6.Mao, J, Chen, LL. Gabapentin in pain management. Anesth Analg 2000; 91: 680–687.CrossRefGoogle ScholarPubMed
7.Dirks, J, Fredensborg, BB, Christensen, D, Flyger, H, Dahl, JB. A randomized study of the effects of single-dose gabapentin versus placebo on postoperative pain and morphine consumption after mastectomy. Anesthesiology 2002; 97: 560–564.CrossRefGoogle ScholarPubMed
8.Gilren, I. Is gabapentin a “broad spectrum” analgesic? Anaesthesia 2002; 97: 537–539.CrossRefGoogle Scholar
9.Partridge, BJ, Chaplan, SR, Sakamoto, E, Yaksh, TL. Characterization of the effects of gabapentin and 3-isobutyl-gamma-aminobutyric acid on substance P-induced thermal hyperalgesia. Anesthesiology 1998; 88: 196–205.CrossRefGoogle ScholarPubMed
10.Christensen, D, Gautron, M, Guilbaud, G, Kayser, V. Effect of gabapentin and lamotrigine on mechanical allodynia-like behaviour in a rat model of trigeminal neuropathic pain. Pain 2001; 93: 147–153.CrossRefGoogle Scholar
11.Takasaki, I, Andoh, T, Nojima, H, Shiraki, K, Kuraishi, Y. Gabapentin antinociception in mice with acute herpetic pain induced by herpes simplex virus infection. J Pharmacol Exp Ther 2001; 296: 270–275.Google ScholarPubMed
12.Yasuda, T, Miki, S, Yoshinaga, N, Senba, E. Effects of amitriptyline and gabapentin on bilateral hyperalgesia observed in an animal model of unilateral axotomy. Pain 2005; 115: 161–170.CrossRefGoogle Scholar
13.Gustafsson, H, Flood, K, Berge, OG, Brodin, E, Olgart, L, Stiller, CO. Gabapentin reverses mechanical allodynia induced by sciatic nerve ischemia and formalin-induced nociception in mice. Exp Neurol 2003; 182: 427–434.CrossRefGoogle ScholarPubMed
14.Shannon, HE, Eberle, EL, Peters, SC. Comparison of the effects of anticonvulsant drugs with diverse mechanisms of action in the formalin test in rats. Neuropharmacology 2005; 48: 1012–1020.CrossRefGoogle ScholarPubMed
15.Feng, Y, Cui, M, Willis, WD. Gabapentin markedly reduces acetic acid-induced visceral nociception. Anesthesiology 2003; 98: 729–733.CrossRefGoogle ScholarPubMed
16.Turan, A, Karamanlioglu, B, Memis, D et al. . Analgesic effects of gabapentin after spinal surgery. Anesthesiology 2004; 100: 935–938.CrossRefGoogle ScholarPubMed
17.Grabow, TS, Dougherty, PM. Gabapentin produces dose-dependent antinociception in the orofacial formalin test in the rat. Reg Anesth Pain Med 2002; 27: 277–283.Google ScholarPubMed
18.Lin, JA, Lee, MS, Wu, CT et al. . Attenuation of morphine tolerance by intrathecal gabapentin is associated with suppression of morphine-evoked excitatory amino acid release in the rat spinal cord. Brain Res 2005; 1054: 167–173.CrossRefGoogle ScholarPubMed
19.Smiley, MM, Lu, Y, Vera-Portocarrero, LP, Zidan, A, Westlund, KN. Intrathecal gabapentin enhances the analgesic effects of subtherapeutic dose morphine in a rat experimental pancreatitis model. Anesthesiology 2004; 101: 759–765.CrossRefGoogle Scholar
20.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: 185–189.CrossRefGoogle ScholarPubMed
21.Pakulska, W, Czarnecka, E. The effect of gabapentin on antinociceptive action of analgesics. Acta Pol Pharm 2004; 61: 393–400.Google ScholarPubMed
22.Al-Mujadi, H, Refai, AR, Katzarov, MG, Dehrab, NA, Batra, YK, Al-Qattan, AR. Preemptive gabapentin reduces postoperative pain and opioid demand following thyroid surgery. Can J Anaesth 2006; 53: 268–273.CrossRefGoogle ScholarPubMed
23.Sasaki, K, Smith, CP, Chuang, YC, Lee, JY, Kim, JC, Chancellor, MB. Oral gabapentin (neurontin) treatment of refractory genitourinary tract pain. Tech Urol 2001; 7: 47–49.Google ScholarPubMed
24.Phatak, S, JrFoster, HE. The management of interstitial cystitis: an update. Nat Clin Pract Urol 2006; 3: 45–53.CrossRefGoogle ScholarPubMed
25.Hansen, HC. Interstitial cystitis and the potential role of gabapentin. South Med J 2000; 93: 238–242.CrossRefGoogle ScholarPubMed
26.Lee, KJ, Kim, JH, Cho, SW. Gabapentin reduces rectal mechanosensitivity and increases rectal compliance in patients with diarrhoea-predominant irritable bowel syndrome. Aliment Pharmacol Ther 2005; 22: 981–988.CrossRefGoogle ScholarPubMed
27.Korster, R, Anderson, M, de Veer, EJ. Acetic acid for analgesic screening. Fed Pro 1959; 18: 412.Google Scholar
28.Friese, N, Chevalier, E, Angel, F et al. . Reversal by kappa-agonists of peritoneal irritation-induced ileus and visceral pain in rats. Life Sci 1997; 60: 625–634.CrossRefGoogle ScholarPubMed
29.Sabetkasaie, M, Vala, S, Khansefid, N, Hosseini, AR, Sadat Ladgevardi, MA. Clonidine and guanfacine-induced antinociception in visceral pain: possible role of alpha 2/I2 binding sites. Eur J Pharmacol 2004; 501: 95–101.CrossRefGoogle ScholarPubMed
30.Shimoyama, M, Shimoyama, N, Hori, Y. Gabapentin affects glutamatergic excitatory neurotransmission in the rat dorsal horn. Pain 2000; 85: 405–414.CrossRefGoogle ScholarPubMed
31.Carlton, SM, Zhou, S. Attenuation of formalin-induced nociceptive behaviors following local peripheral injection of gabapentin. Pain 1998; 76: 201–207.CrossRefGoogle ScholarPubMed
32.Picazo, A, Castaneda-Hernandez, G, Ortiz, MI. Examination of the interaction between peripheral diclofenac and gabapentin on the 5% formalin test in rats. Life Sci 2006; 79: 2283–2287.CrossRefGoogle ScholarPubMed
33.Todorovic, SM, Rastogi, AJ, Jevtovic-Todorovic, V. Potent analgesic effects of anticonvulsants on peripheral thermal nociception in rats. Br J Pharmacol 2003; 140: 255–260.CrossRefGoogle ScholarPubMed
34.Ortiz, MI, Medina-Tato, DA, Sarmiento-Heredia, D, Palma-Martinez, J, Granados-Soto, V. Possible activation of the NO–cyclic GMP–protein kinase G–K+ channels pathway by gabapentin on the formalin test. Pharmacol Biochem Behav 2006; 83: 420–427.CrossRefGoogle ScholarPubMed
35.Granados-Soto, V, Rufino, MO, Gomes Lopes, LD, Ferreira, SH. Evidence for the involvement of the nitric oxide–cGMP pathway in the antinociception of morphine in the formalin test. Eur J Pharmacol 1997; 340: 177–180.CrossRefGoogle ScholarPubMed
36.Reichert, JA, Daughters, RS, Rivard, R, Simone, DA. Peripheral and preemptive opioid antinociception in a mouse visceral pain model. Pain 2001; 89: 221–227.CrossRefGoogle Scholar
37.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: 1263–1273.CrossRefGoogle ScholarPubMed
38.Fink, K, Meder, W, Dooley, DJ, Gothert, M. Inhibition of neuronal Ca2+ influx by gabapentin and subsequent reduction of neurotransmitter release from rat neocortical slices. Br J Pharmacol 2000; 130: 900–906.CrossRefGoogle ScholarPubMed
39.Shimoyama, M, Shimoyama, N, Inturrisi, CE, Elliott, KJ. Gabapentin enhances the antinociceptive effects of spinal morphine in the rat tail-flick test. Pain 1997; 72: 375–382.CrossRefGoogle ScholarPubMed
40.Burton, MB, Gebhart, GF. Effects of kappa-opioid receptor agonists on responses to colorectal distension in rats with and without acute colonic inflammation. J Pharmacol Exp Ther 1998; 285: 707–715.Google ScholarPubMed
41.Sora, I, Li, XF, Funada, M, Kinsey, S, Uhl, GR. Visceral chemical nociception in mice lacking mu-opioid receptors: effects of morphine, SNC80 and U-50,488. Eur J Pharmacol 1999; 366: R3–R5.CrossRefGoogle ScholarPubMed
42.Shamsi Meimandi, MS, Mobasher, M, Sepehri, GR, Ashrafganjooei, N. Gabapentin increases analgesic effect of chronic use of morphine while decreases withdrawal signs. Int J Pharmacolo 2005; 1: 161–165.CrossRefGoogle Scholar