Hostname: page-component-cd9895bd7-lnqnp Total loading time: 0 Render date: 2024-12-22T23:42:22.098Z Has data issue: false hasContentIssue false

Antiallodynia and antihyperalgesia effects of ceftriaxone in treatment of chronic neuropathic pain in rats

Published online by Cambridge University Press:  22 February 2013

Valiollah Hajhashemi
Affiliation:
Isfahan Pharmaceutical Sciences Research Center, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
Hossein Hosseinzadeh
Affiliation:
Pharmaceutical Research Center, Pharmacodynamy and Toxicology Department, School of Pharmacy, Mashhad University of Medical Sciences, Mashhad, IR, Iran
Bahareh Amin*
Affiliation:
Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran
*
Bahareh Amin, Department of Pharmacology, School of Pharmacy and Pharmaceutical Sciences, Isfahan University of Medical Sciences, Isfahan, Iran. Tel: +983117922630; Fax: +983116680011; E-mail: [email protected]

Abstract

Objective

Neuropathic pain is a chronic and disabling syndrome with complex pathogenesis. It has been suggested that the function of glutamate transporters (GLTs) has a major role in the development of neuropathic pain. This study was performed to evaluate various doses of ceftriaxone, a beta-lactam antibiotic, on the symptoms in the rat chronic constriction injury (CCI) model of neuropathic pain. This drug has been recently introduced as a selective up-regulator and activator of GLT1.

Methods

Neuropathy was induced in adult male Wistar rats and animals were treated intraperitoneally with 100–400 mg/kg of ceftriaxone for seven consecutive days immediately after surgery. Gabapentin (100 mg/kg, i.p.) was used as a reference drug. von Frey filaments, acetone drop and radiant heat methods were used to assess mechanical allodynia, thermal allodynia and thermal hyperalgesia, respectively.

Results

Ceftriaxone in the repeated doses for 7 days showed significant antiallodynic and antihyperalgesic effects especially at a dose of 200 mg/kg twice a day.

Conclusion

The results suggest that ceftriaxone as a modulator of glutamate uptake could provide beneficial effects in the treatment of chronic neuropathic pain, especially allodynia that is less sensitive to the most available drugs.

Type
Original Articles
Copyright
Scandinavian College of Neuropsychopharmacology 2013

Access options

Get access to the full version of this content by using one of the access options below. (Log in options will check for institutional or personal access. Content may require purchase if you do not have access.)

References

1Zimmermann, M.Pathobiology of neuropathic pain. Eur J Pharmacol 2001;429:2337.Google Scholar
2Woolf, CJ, Mannion, RJ.Neuropathic pain: aetiology, symptoms, mechanisms, and management. Lancet 1999;9168:19591964.Google Scholar
3Dworkin, RH, Backonja, M, Rowbotham, MCet al.Advances in neuropathic pain: diagnosis, mechanisms, and treatment recommendations. Arch Neurol 2003;60:15241534.CrossRefGoogle ScholarPubMed
4Fitzgerald, JF, Romero, R, Saberski, LR.Complications of antidepressants, anticonvulsants, and antiarrhythmics for chronic pain management. Tech Reg Anesth Pain Manag 1998;2:119129.CrossRefGoogle Scholar
5Dworkin, R.An overview of neuropathic pain: syndromes, symptoms, signs, and several mechanisms. Clin J Pain 2002;18:343.Google Scholar
6Schafers, M, Marziniak, M, Sorkin, LS, Yaksh, TL, Sommer, C.Cyclooxygenase inhibition in nerve-injury-and TNF-induced hyperalgesia in the rat. Exp Neurol 2004;185:160168.Google Scholar
7Berrocoso, E, de Benito, MD, Mico, JA.Role of serotonin 5-HT 1A and opioid receptors in the antiallodynic effect of tramadol in the chronic constriction injury model of neuropathic pain in rats. Psychopharmacology 2007;193:97105.CrossRefGoogle ScholarPubMed
8Petcu, M, Dias, J, Ongali, B, Thibault, G, Neugebauer, W, Couture, R.Role of kinin B1 and B2 receptors in a rat model of neuropathic pain. Int Immunopharmacol 2008;8:188196.CrossRefGoogle Scholar
9Whitehite, FA, Jungung, H, Milleriller, RJ.Chemokines and the pathophysiology of neuropathic pain. Proc Natl Acad Sci U S A 2007;104:2015120158.CrossRefGoogle Scholar
10Coderre, TJ.The role of excitatory amino acid receptors and intracellular messengers in persistent nociception after tissue injury in rats. Mol Neurobiol 1993;7:229246.Google Scholar
11Procter, AW, Lowe, SL, Palmer, AMet al.Topographical distribution of neurochemical changes in Alzheimer's disease. J Neurol Sci 1988;84:125140.CrossRefGoogle ScholarPubMed
12Mcdonald, JW, Johnston, MV.Physiological and pathophysiological roles of excitatory amino acids during central nervous system development. Brain Res Rev 1990;15:4170.CrossRefGoogle ScholarPubMed
13Mayer, ML, Westbrook, GL.The physiology of excitatory amino acids in the vertebrate central nervous system. Prog Neurobiol 1987;28:197276.Google Scholar
14Beart, PM, O’Shea, RD.Transporters for L glutamate: an update on their molecular pharmacology and pathological involvement. Br J Pharmacol 2007;150:517.Google Scholar
15Sung, B, Lim, G, Mao, J.Altered expression and uptake activity of spinal glutamate transporters after nerve injury contribute to the pathogenesis of neuropathic pain in rats. J Neurosci 2003;23:28992910.CrossRefGoogle Scholar
16Mirzaei, V, Manaheji, H, Maghsoudi, N, Zaringhalam, J.Comparison of changes in mRNA expression of spinal glutamate transporters following induction of two neuropathic pain models. Spinal Cord 2010;48:791797.Google Scholar
17Rothstein, JD, Patel, S, Regan, MRet al.Beta-Lactam antibiotics offer neuroprotection by increasing glutamate transporter expression. Nature 2005;433:7377.Google Scholar
18Hu, Y, Li, W, Lu, Let al.An anti-nociceptive role for ceftriaxone in chronic neuropathic pain in rats. Pain 2010;148:284301.CrossRefGoogle ScholarPubMed
19Zimmermann, M.Ethical guidelines for investigation of experimental pain in conscious animals. Pain 1983;16: 109110.CrossRefGoogle ScholarPubMed
20Bennett, GJ, Xie, YK.A peripheral mononeuropathy in rat that produces disorders of pain sensation like those seen in man. Pain 1988;33:87107.Google Scholar
21Stuesse, SL, Crisp, T, Mcburney, DL, Schechter, JB, Lovell, JA, Cruce, WL.Neuropathic pain in aged rats: behavioral responses and astrocytic activation. Exp Brain Res 2001;137:219227.Google Scholar
22Choi, Y, Yoon, YW, Na, HS, Kim, SH, Chung, JM.Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain 1994;59:369376.Google Scholar
23Hargreaves, K, Dubner, R, Brown, F, Flores, C, Joris, J.A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain 1988;32:7788.Google Scholar
24Esser, MJ, Chase, T, Allen, GV, Sawynok, J.Chronic administration of amitriptyline and caffeine in a rat model of neuropathic pain: multiple interactions. Eur J Pharmacol 2001;430:211218.Google Scholar
25Esser, MJ, Sawynok, J.Acute amitriptyline in a rat model of neuropathic pain: differential symptom and route effects. Pain 1999;80:643653.CrossRefGoogle Scholar
26Hofmann, HA, de Vry, J, Siegling, A, Spreyer, P, Denzer, D.Pharmacological sensitivity and gene expression analysis of the tibial nerve injury model of neuropathic pain. Eur J Pharmacol 2003;470:1725.Google Scholar
27Goh, KP.Management of hyponatremia. Am Fam physician 2004;69:2387.Google Scholar
28Dworkin, RH, O’Connor, AB, Backonja, Met al.Pharmacologic management of neuropathic pain: evidence-based recommendations. Pain 2007;132:237251.Google Scholar
29Chonghong, MS, Brandner, B.Neuropathic agents and pain. New strategies. Biomed Pharmacother 2006;60: 318322.Google Scholar