EFFECTS OF CHRONIC DOXEPIN AND AMITRIPTYLINE ADMINISTRATION IN NAIVE MICE AND IN NEUROPATHIC PAIN MICE MODEL
PBN-AR
Instytucja
Instytut Farmakologii im. Jerzego Maja Polskiej Akademii Nauk
Informacje podstawowe
Główny język publikacji
angielski
Czasopismo
NEUROSCIENCE
ISSN
0306-4522
EISSN
Wydawca
ELSEVIER
DOI
Rok publikacji
2015
Numer zeszytu
Strony od-do
38-59
Numer tomu
294
Liczba arkuszy
Słowa kluczowe
en
interleukin-6
interleukin-1 beta
ondansetron
antidepressants
yohimbine
pain
Streszczenia
Język
en
Treść
Neuropathic pain is a severe clinical problem, often appearing as a co-symptom of many diseases or manifesting as a result of damage to the nervous system. Many drugs and agents are currently used for the treatment of neuropathic pain, such as tricyclic antidepressants (TCAs). The aims of this paper were to test the effects of two classic TCAs, doxepin and amitriptyline, in naive animals and in a model of neuropathic pain and to determine the role of cytokine activation in the effects of these drugs. All experiments were carried out with Albino-Swiss mice using behavioral tests (von Frey test and the cold plate test) and biochemical analyses (qRT-PCR and Western blot). In the mice subjected to chronic constriction injury (CCI), doxepin and amitriptyline attenuated the symptoms of neuropathic pain and diminished the CCI-induced increase in the levels of spinal interleukin (IL)-6 and -1 beta mRNA, but not the protein levels of these cytokines, measured on day 12. Unexpectedly, chronic administration of doxepin or amitriptyline for 12 days produced allodynia and hyperalgesia in naive mice. The treatment with these drugs did not influence the spinal levels of IL-1 beta and IL-6 mRNA, however, the protein levels of these pronociceptive factors were increased. The administration of ondansetron (5-HT3 receptor antagonist) significantly weakened the allodynia and hyperalgesia induced by both antidepressants in naive mice; in contrast, yohimbine (alpha 2-adrenergic receptors antagonist) did not influence these effects. Allodynia and hyperalgesia induced in naive animals by amitriptyline and doxepin may be associated with an increase in the levels of pronociceptive cytokines resulting from 5-HT3-induced hypersensitivity. Our results provide new and important information about the possible side effects of antidepressants. Further investigation of these mechanisms may help to guide decisions about the use of classic TCAs for therapy. (C) 2015 IBRO. Published by Elsevier Ltd. All rights reserved.
Cechy publikacji
ORIGINAL_ARTICLE
Inne
System-identifier
659827
CrossrefMetadata from Crossref logo
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