Chronic dizocilpine or apomorphine and development of neuropathy in two animal models II

Effects on brain cytokines and neurotrophins

Hassen Al Amin, Rani Sarkis, Samir Atweh, Suhayl Jabbur, Nayef Saadé

Research output: Contribution to journalArticle

41 Citations (Scopus)

Abstract

Dopaminergic and glutamatergic mechanisms are involved in the development and modulation of neuropathy. Cytokines and neurotrophins can be also involved in the supraspinal maintenance of neuropathic pain. We assessed the effects of chronic intraperitoneal (ip) injection of dizocilpine (MK-801), a N-methyl- d-Aspartate (NMDA) noncompetitive receptor antagonist, or apomorphine (APO), a dopamine (DA) D1 and D2 receptor agonist, on neuropathic manifestations in the chronic constriction injury (CCI) and the spared nerve injury (SNI) models of neuropathy in rats. Six groups of rats were subjected to SNI or CCI (3 groups each) neuropathy and 5-7 days later received daily ip injections of saline, MK-801, or APO for two weeks. An additional control group was subjected to sham surgery without nerve lesion or injections. Rats were then sacrificed, and levels of IL-1β, IL-6, NGF, BDNF and GDNF were determined in the cingulum, striatum, and hippocampus. In both models, the neuropathy seen in the saline group was associated with decreased BDNF and an increase in IL-1β, IL-6, NGF and GDNF in most brain regions when compared to sham group. Chronic systemic MK-801 or APO injections decreased the neuropathic manifestations in both models, increased the BDNF level and modulated the other cytokines and neurotrophins. This modulation depended on the neuropathy model and the region/side of the brain studied. Our results showed that the changes in surpraspinal cytokines and neurotrophins could parallel neuropathic manifestations. These changes and the observed hyperalgesia can be modulated by chronic systemic injections of NMDA antagonists or DA agonists.

Original languageEnglish
Pages (from-to)30-40
Number of pages11
JournalExperimental Neurology
Volume228
Issue number1
DOIs
Publication statusPublished - Mar 2011

Fingerprint

Dizocilpine Maleate
Apomorphine
Nerve Growth Factors
Brain-Derived Neurotrophic Factor
Animal Models
Cytokines
Glial Cell Line-Derived Neurotrophic Factor
Wounds and Injuries
Brain
Nerve Growth Factor
Intraperitoneal Injections
Interleukin-1
Constriction
Injections
Interleukin-6
Dopamine D1 Receptors
Dopamine D2 Receptors
Hyperalgesia
Dopamine Agonists
Neuralgia

Keywords

  • Cytokines
  • Dopamine
  • Glutamate
  • Neuropathy
  • Neurotrophins

ASJC Scopus subject areas

  • Neurology
  • Developmental Neuroscience

Cite this

Chronic dizocilpine or apomorphine and development of neuropathy in two animal models II : Effects on brain cytokines and neurotrophins. / Al Amin, Hassen; Sarkis, Rani; Atweh, Samir; Jabbur, Suhayl; Saadé, Nayef.

In: Experimental Neurology, Vol. 228, No. 1, 03.2011, p. 30-40.

Research output: Contribution to journalArticle

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