Please cite this article in press as: Karami, M., et al., Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP). Phytomedicine (2013), http://dx.doi.org/10.1016/j.phymed.2013.07.013 ARTICLE IN PRESS G Model PHYMED-51481; No. of Pages 6 Phytomedicine xxx (2013) xxx–xxx Contents lists available at ScienceDirect Phytomedicine j ourna l h o mepage: www.elsevier.de/phymed Crocin improved locomotor function and mechanical behavior in the rat model of contused spinal cord injury through decreasing calcitonin gene related peptide (CGRP) Masoume Karami a , S. Zahra Bathaie a,∗ , Taqi Tiraihi b,c , Mehran Habibi-Rezaei d , Jalil Arabkheradmand b , Soghrat Faghihzadeh e a Department of Clinical Biochemistry, Faculty of Medical Sciences, Tarbiat Modares University, Tehran, Iran b Shefa Neuroscience Research Center, Khatam al-Anbia Hospital, Tehran, Iran c Department of Anatomic Sciences, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran d Department of Molecular Biology, School of Biology, College of Science, University of Tehran, Tehran, Iran e Department of Biostatistics, School of Medical Sciences, Tarbiat Modares University, Tehran, Iran a r t i c l e i n f o Article history: Received 10 December 2012 Received in revised form 29 June 2013 Accepted 29 July 2013 Keywords: Crocin Spinal cord injury Mechanical behavioral test Locomotor recovery test Thermal behavioral test a b s t r a c t Various approaches have been offered to alleviate chronic pain resulting from spinal cord injuries (SCIs). Application of herbs and natural products, with potentially lower adverse effects, to cure diseases has been recommended in both traditional and modern medicines. Here, the effect of crocin on chronic pain induced by spinal cord contusion was investigated in an animal model. Female Wistar rats were randomly divided into five groups (5 rats in each); three groups were contused at the L1 level. One group was treated with crocin (150 mg/kg) two weeks after spinal cord injury; the second group, control, was treated with vehicle only; and the third group was treated with ketoprofen. Two normal groups were also considered with or without crocin treatment. The mechanical behavioral test, the locomotor recovery test and the thermal behavioral test were applied weekly to evaluate the injury and recovery of rats. Significant improvements (p < 0.05) in mechanical behavioral and locomotor recovery tests were seen in the rats treated with crocin. Thermal behavioral test did not show any significant changes due to crocin treatment. Plasma concentration of calcitonin-gene related peptide (CGRP) changed from 780.2 ± 2.3 to 1140.3 ± 4.5 pg/ml due to SCI and reached 789.1 ± 2.7 pg/ml after crocin treatment. These changes were significant at the level of p < 0.05. The present study shows the beneficial effects of crocin treatment on chronic pain induced by SCI, through decreasing CGRP as an important mediator of inflammation and pain. © 2013 Elsevier GmbH. All rights reserved. Introduction Pain is a distressing sensation that can act as an alert mechanism preventing further or impending tissue injury. Pain has been classi- fied according to cause as nociceptive or neuropathic and according to duration as acute or chronic (Marchand 2008). Acute pain may not require medical attention; however, when required, nonsteroidal anti-inflammatory drugs (NSAIDs) such as aspirin, opioid analgesics, or local anesthetics can be used (Massey et al. 2010). Almost all of the currently available analgesics on the market were initially developed to control acute pain. Chronic neuropathic pain differs from acute pain in duration and mode ∗ Corresponding author at: Department of Clinical Biochemistry, Faculty of Med- ical Sciences, Tarbiat Modares University, P.O. Box: 14115-111, Tehran, Iran. Tel.: +98 21 8288-3850. E-mail addresses: bathai z@modares.ac.ir, zbatha2000@yahoo.com (S.Z. Bathaie). of onset, and more importantly in the underlying mechanism leading to manifestation. Hence, the best approach for controlling and alleviating chronic pain requires a clear understanding of the mechanisms involved and in vivo testing of pharmacological agents (Gonzalez-Nunez and Rodriguez 2009). Animal models offer the most useful and essential systems for studying chronic pain and its treatment. Numerous animal models have been developed to simulate specific human painful conditions, mostly by producing disease or traumatic injuries that have painful sequelae (Vallin and Kingery 1991; Wang and Wang 2003). Neuropathic pain is associated with diseases such as multiple sclerosis, diabetic neuropathy, shingles, post herpetic neuralgia, and stroke as well as mechanical injuries such as amputation, brain trauma, and spinal cord injury (SCI) (Kalderon et al. 2007). Certain features of human injury can be reproduced through contusion models in rodents. Many behavioral tests for evaluating SCI and functional recovery in rodents, especially in the rat, have been developed, including the Basso, Beattie, and Bresnahan scale (or BBB test) (Basso et al. 1996), ladder climb, grid walk, inclined plane, 0944-7113/$ – see front matter © 2013 Elsevier GmbH. 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