|
" Evaluation the anti-inflammatory and anti-nociceptive effects of intraperitoneal and intracerebroventricular administration of venlafaxine in a rat model of inflammatory paw edema and neuropathic pain and determining the role of opioid, adenosine and a2-adrenergic receptors in its antinociceptive effects "
/علیرضا عابد
; Valiollah Hajhashemi, Mohsen Minaiyan, Hamid Reza Banafshe
| center
|
:
|
Isfahan University of Medical Sciences
|
| Document Type
|
:
|
Latin Dissertation
|
| Language of Document
|
:
|
English
|
| Record Number
|
:
|
103541
|
| Doc. No
|
:
|
T15330
|
| Call number
|
:
|
QV,77.5,A138e,2015
|
| Main Entry
|
:
|
Abed, Alireza
|
| Title & Author
|
:
|
Evaluation the anti-inflammatory and anti-nociceptive effects of intraperitoneal and intracerebroventricular administration of venlafaxine in a rat model of inflammatory paw edema and neuropathic pain and determining the role of opioid, adenosine and a2-adrenergic receptors in its antinociceptive effects/علیرضا عابد
|
| College
|
:
|
Schools, Pharmacy
|
| Date
|
:
|
, 2015
|
| Degree
|
:
|
Pharmacology, Ph.D
|
| Page No
|
:
|
xii, 145p.: ill., diag. tab
|
| Note
|
:
|
This is a dissertation research with project ID: 393216
|
| Abstract
|
:
|
Recently the anti-inflammatory and antinociceptive effects of antidepressant drugs especially tricyclic antidepressants (TCA) have been demonstrated. Venlafaxine belongs to newer antidepressants with serotonin/norepinephrine reuptake inhibition property. Moreover venlafaxine does not induce the usual tricyclic antidepressants (TCAs) side-effects caused by their anticholinergic, anti-histaminic and alpha-1 adrenergic antagonistic properties. The present study was designed to determine the anti-inflammatory and antinociceptive effects of venlafaxine and its underlying mechanisms in a rat model of inflammatory paw edema and peripheral neuropathic pain. Materials and methods: Male Wistar rats weighing 220-270 were used in this study. Neuropathic pain was induced by chronic constriction injury (CCI) of the sciatic nerve in the rats that resulted in stimulus-evoked thermal hyperalgesia, tactile mechanical and cold allodynia. To compare early versus late treatment we have designed three different treatment protocols; intermittent treatment, daily treatment immediately after nerve injury for 14 days and repeated treatment after the model had fully established, for additional 11 days. To identify the role of a2-adrenoceptor in the anti-nociceptive effects of venlafaxine in the peripheral neuropathic pain we have examined effect of yohimbine a2 adrenoceptor antagonist on the anti-nociceptive effects of venlafaxine on the heat, cold and mechanical hyperalgesia in rats. Inflammatory paw edema was induced by injection of 100 ml suspension of carrageenan lambda (1 percent w/v) subplantar in the right hind paw. ELISA protocol was used for determining cytokines contents in the hind paw. Results: Acute venlafaxine injections (20 and 40 mg/kg i.p.) on the 7th, 14th and 21st postoperative days did not significantly reduce tactile and cold hypersensitivity compared to CCI group. But in these groups venlafaxine (40 mg/kg i.p.) blocked heat hyperalgesia. When venlafaxine (10 and 20 mg/kg i.p.) administration was started on the first day after CCI and given daily until the 14th day, tactile hypersensitivity and heat hyperalgesia were considerably attenuated. But when venlafaxine (20 mg/kg i.p.) treatment was initiated on the 10th day after CCI, no difference in withdrawal threshold was observed compared with CCI group however heat hyperalgesia has been blocked significantly. Also the effect of venlafaxine on heat hyperalgesia was reversed by pretreatment with yohimbine at all-time intervals. Also this effect was not blocked by concomitant caffeine or naloxone administration. Both intraperitoneal (50 and 100 mg/kg i.p.) and intracerebroventricular (50 and 100 mg/rat i.c.v.) injection of venlafaxine inhibited carrageenan-induced paw edema. Also i.p. and i.c.v. administration of venlafaxine significantly decreased myeloperoxidase (MPO) activity, interleukin (IL)-1B and tumor necrosis factor (TNF)-a- production. We used yohimbine (5 mg/kg i.p.), an alpha2-adrenergic antagonist, to reverse the anti-inflammatory effect of venlafaxine. Our results showed that the applied antagonists failed to reverse the anti-inflammatory effect of venlafaxine. Finally we have compared antinociceptive effects of venlafaxine with maprotiline and amitriptyline. Our result showed that acute venlafaxine injection has weak antinociceptive effects compared to maprotiline and amitriptyline. Conclusion: These results indicate that venlafaxine, when administered immediately after nerve injury, and for a sufficient period of time, can prevent the development and expression of neuropathic pain. Also we conclude that ?2-adrenoceptors participate in the antinociceptive effects of venlafaxine and this effect is independent of adenosine or opioid system. This observation demonstrates that venlafaxine, which is a mixed inhibitor of norepinephrine and serotonin reuptake, differs from the other antidepressants in the mechanism of its antinociception action. Considering our results venlafaxine has potent anti-inflammatory effect which is linked to the peripheral and central effects of this drug. We also showed that anti-inflammatory effect of venlafaxine mediated mostly through the inhibition the IL-1? and TNF-? production and decreased myeloperoxidase (MPO) activity in the site of inflammation. At last we showed that amitriptyline and maprotiline have more antinociceptive effects than venlafaxine. But it should be considered that venlafaxine has fewer side effects and is better tolerated by patients.
|
| Descriptor
|
:
|
Antidepressive Agents, Second-Generation
|
|
|
:
|
Analgesics
|
|
|
:
|
Adrenergic alpha-Agonists
|
|
|
:
|
Pain
|
| Added Entry
|
:
|
Hajhashemi, Valiollah, Supervisor
|
|
|
:
|
Minaiyan, Mohsen, Supervisor
|
|
|
:
|
Banafshe, Hamid Reza, Supervisor
|
| |