J Exp Clin Neurosci, 2019, 6(1): 1-5
1
Original Artcle
Cerebrolysin Ameliorates Cisplatin-Induced Neuropathic Pain in Mice: A Behavioral Study
Ali Namvaran-Abbas-Abad
a
, Fereshteh Farajdokht
b
, Saeed Sadigh-Eteghad
b
, Javad Mahmoudi
b
, Seyed Mahdi Vatandoost
b,
*
a
Hematology and Oncology Research Center, Tabriz University of Medical Sciences, Tabriz, Iran
b
Neurosciences Research Center (NSRC), Tabriz University of Medical Sciences, Tabriz, Iran
Introduction
Neuropathic pain is a chronic pain condition affecting millions of
individuals worldwide [1]. This condition is caused by different
ailments, such as diabetes [2], injuries, and interventions [3-5],
that affect the somatosensory system [1]. Chronic pain results
in a great many of these cases [6]. Chemotherapy-induced
peripheral neuropathy (CIPN) is a troublesome chronic condition
experienced by 30% to 40 % of patients undergoing sequential
chemotherapy, and it remains as a common dose-limiting side
effect of chemotherapeutic agents [3, 7]. Moreover, CIPN may
have negative consequences on treatment procedures [8], quality
of life, and daily activities [3, 7, 8]. Unfortunately, little is known
about CIPN’ss exact pathophysiology, and available treatments
have a restricted effciency in relieving pain [8].
Cisplatin is a potent chemotherapeutic agent used to treat a
wide range of solid tumors, including testicular, ovarian, and
bladder cancers [9]. The aadministration of cisplatin is also
associated with neurotoxicity via irreversible axonal loss [10]
and with neuropathic pain in distal extremities [11]. Cisplatin is
extensively used as an animal model of neuropathy pain to study
the effects of neuroprotective substances [11-13]. However, pain
management remains a major challenge that restricts cisplatin use
in clinical settings. In addition, currently available therapies are
not able to effectively control neuropathic pain symptoms [11, 14].
Cerebrolysin (CBL) is a purifed mixture containing a fraction
of free amino acids and some brain growth factors [15], including
brain-derived neurotrophic factor (BDNF), glial cell line-derived
neurotrophic factor (GDNF), nerve growth factor (NGF), and
ciliary neurotrophic factor (CNTF) [16]. Evidence shows that CBL
is capable of partially crossing the blood-brain barrier because it
contains low molecular weight peptides. Previous research has
shown that CBL improves different neurological conditions,
Abstract
Objectve: Cisplatn (Cis) is a potent chemotherapeutc agent in clinical use which is associated with
nephrotoxicity and neuropathic pain possibly through infammatory response. Cerebrolysin (CBL), a
mixture of neurotrophins, has analgesic and ant-infammatory propertes. The aim of the present study
was to investgate the efects of cerebrolysin on cisplatn-induced neuropathic pain in mice.
Materials and Methods: Mice were randomly divided into fve groups: Control, Cis, Cis + CBL, Cis +
Vitamin E (Vit E), and Cis + Morphine. CBL and Vit E were injected for four consecutve days following a
single injecton of Cis. On day 4, the mice were subjected to three behavioral tests: cold plate, hot plate,
and formalin.
Results: The results showed that mice treated with CBL had higher withdrawal thresholds for both the
hot plate and cold plate tests and displayed lower hyperalgesia-related behaviors for the formalin test
compared to the Cis group. Moreover, CBL induced higher ant-nociceptve efects than Vit E and lesser
efects than morphine in both hot plate and cold plate tests. Furthermore, the analgesic efect of CBL was
similar to the morphine efect in the late phase of the formalin test.
Conclusion: These results indicate that CBL has an ant-nociceptve efect against cisplatn-induced
neuropathic pain.
Keywords: Cisplatn, Neuropathic Pain, Cerebrolysin, Hyperalgesia
©2019 Swedish Science Pioneers, All rights reserved.
Correspondence
Seyed Mahdi Vatandoust
Neurosciences research center (NSRC),
Tabriz University of Medical Sciences,
Tabriz, Iran. Tel/Fax: +984133340730.
Email: sm.vatandoust@gmail.com
Received: 2018-10-10
Accepted: 2018-11-01
DOI:10.13183/jecns.v6i1.85