Summary
Chemotherapy-induced neuropathy is a serious clinical problem for patients receiving cancer treatment. The aim of this study was to investigate the potential efficacy of pregabalin in chemotherapy-induced neuropathy in rats. A total of 35 male Sprague-Dawley rats were randomly divided into 5 groups: group 1, naive control; group 2, treated with pregabalin (30 mg/kg p.o., for 8 days); group 3, docetaxel was given by single intravenous infusion at 10 mg/kg; groups 4 and 5, pregabalin at 10 mg/kg and 30 mg/kg respectively was orally administered for 8 days after the docetaxel treatment. On day 8, behavioral test was performed, and substance P and CGRP release in dorsal root ganglion (DRG) and sciatic nerve were analyzed by electron microscope. Our results showed that docetaxel induced mechanical allodynia, mechanical hyperalgesia, heat hypoalgesia, cold allodynia, and sciatic nerve impairment and substance P and CGRP release in DRG. However, oral administration of pregabalin (10 mg/kg and 30 mg/kg) for 8 consecutive days significantly attenuated docetaxel-induced neuropathy by ameliorating heat hypoalgesia, cold allodynia, impairment of sciatic nerve and reducing the release of substance P and CGRP. The findings in the present study reveal that pregabalin may be a potential treatment agent against chemotherapy-induced neuropathy.
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Dworkin RH, O’Connor AB, Audette J, et al. Recommendations for the pharmacological management of neuropathic pain: an overview and literature update. Mayo Clin Proc, 2010,85(3 Suppl):S3–14
Anastassiou E, Iatrou CA, Vlaikidis N, et al. Impact of pregabalin treatment on pain, pain-related sleep interference and general well-being in patients with neuropathic pain: a non-interventional, multicentre, post-marketing study. Clin Drug Investig, 2011,31(6): 417–426
Cavaletti G, Marmiroli P. Chemotherapy-induced peripheral neurotoxicity. Nat Rev Neurol, 2010,6(12): 657–666
Olesen SS, Bouwense SA, Wilder-Smith OH, et al. Pregabalin reduces pain in patients with chronic pancreatitis in a randomized, controlled trial. Gastroent erology, 2011,141(2):536–543
Zimmermann M. Ethical guidelines for investigations of experimental pain in conscious animals. Pain, 1983,16(2): 109–110
Stopponi S, Somaini L, Cippitelli A, et al. Pregabalin reduces alcohol drinking and relapse to alcohol seeking in the rat. Psychopharmacology (Berl), 2011
Pinkel D. The use of body surface area as a criterion of drug dosage in cancer chemotherapy. Cancer Res, 1958,18(7):853–856
Meng X, Zhang Y, Li A, et al. The effects of opioid receptor antagonists on electroacupuncture-produced anti-allodynia/hyperalgesia in rats with paclitaxel-evoked peripheral neuropathy. Brain Res, 2011,1414:58–65
Hargreaves K, Dubner R, Brown F, et al. A new and sensitive method for measuring thermal nociception in cutaneous hyperalgesia. Pain, 1988,32(1):77–88
Choi Y, Yoon YW, Na HS, et al. Behavioral signs of ongoing pain and cold allodynia in a rat model of neuropathic pain. Pain, 1994,59(3):369–376
Zhang J, Chen L, Su T, et al. Electroacupuncture increases CB2 receptor expression on keratinocytes and infiltrating inflammatory cells in inflamed skin tissues of rats. J Pain, 2010,11(12):1250–1258
Persohn E, Canta A, Schoepfer S, et al. Morphological and morphometric analysis of paclitaxel and docetaxel-induced peripheral neuropathy in rats. Eur J Cancer, 2005,41(10):1460–1466
Vorobeychik Y, Gordin V, Mao J, et al. Combination Therapy for Neuropathic Pain: A Review of Current Evidence. CNS Drugs, 2011
Bril V, England J, Franklin GM, et al. Evidence-based guideline: Treatment of painful diabetic neuropathy: report of the American Academy of Neurology, the American Association of Neuromuscular and Electrodiagnostic Medicine, and the American Academy of Physical Medicine and Rehabilitation. Neurology, 2011,76(20):1758–1765
Joseph EK, Levine JD. Comparison of oxaliplatin- and cisplatin-induced painful peripheral neuropathy in the rat. J Pain, 2009,10(5):534–541
Authier N, Balayssac D, Marchand F, et al. Animal models of chemotherapy-evoked painful peripheral neuropathies. Neurotherapeutics, 2009,6(4):620–629
Carlson K, Ocean AJ. Peripheral neuropathy with microtubule-targeting agents: occurrence and management approach. Clin Breast Cancer, 2011,11(2): 73–81
Ling B, Authier N, Balayssac D, et al. Behavioral and pharmacological description of oxaliplatin-induced painful neuropathy in rat. Pain, 2007,128(3):225–234
Tatsushima Y, Egashira N, Kawashiri T, et al. Involvement of substance P in peripheral neuropathy induced by paclitaxel but not oxaliplatin. J Pharmacol Exp Ther, 2011,337(1):226–235
Theile JW, Cummins TR. Recent developments regarding voltage-gated sodium channel blockers for the treatment of inherited and acquired neuropathic pain syndromes. Front Pharmacol, 2011,2(54):1–14
Hagiwara H, Sunada Y. Mechanism of taxane neurotoxicity. Breast Cancer, 2004,11(1):82–85
Dougherty PM, Cata JP, Cordella JV, et al. Taxol-induced sensory disturbance is characterized by preferential impairment of myelinated fiber function in cancer patients. Pain, 2004,109(1–2):132–142
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The study was supported by the National Natural Science Foundation of China (Grant No. 81172187).
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Peng, P., Xi, Q., Xia, S. et al. Pregabalin attenuates docetaxel-induced neuropathy in rats. J. Huazhong Univ. Sci. Technol. [Med. Sci.] 32, 586–590 (2012). https://doi.org/10.1007/s11596-012-1001-y
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DOI: https://doi.org/10.1007/s11596-012-1001-y