Minocycline affects neuropathic pain by regulation of kynurenic pathway – role of microglial cells

• Autorzy: Rojewska E. , Piotrowska A. , Jurga A.M. , Makuch W. , Przewlocka B. , Mika J.
• Języki publikacji: EN

Abstrakty

EN

The participation of kynurenine system in the pathology of neurodegenerative and autoimmune diseases was studied, but the significance of this pathway in neuropathic pain have been poorly studied. The kynurenine pathway has already been shown to exist mainly in macrophages and microglia. Growing evidence suggests that spinal microglia are crucial in the neuropathic pain. Minocycline, a microglial inhibitor, is a substances with diverse mechanisms of action that modulate the neuroimmune system have been shown to relieve neuropathic pain. The aim of our study was to examine the role of kynurenine 3-monooxygenase (Kmo) in a rat model of neuropathy. Chronic constriction injury (CCI) of the sciatic nerve was performed according to Bennett and Xie (1988). Behavioral studies consisted of the tactile and thermal hypersensitivity measurements, biochemical studies comprised the RT-PCR and/or Western blot analysis in the tissue (spinal cord, DRG) and primary glia cultures. The experiments were carried out according to IASP rules. Using microarray and qRT-PCR methods, we showed that intraperitoneal administration of minocycline decreased neuropathic pain in rats and in parallel the spinal 3-monooxygenase kynurenine expression (Kmo). Further, minocycline administration diminished the lipopolysaccharide (LPS)-induced upregulation of Kmo mRNA in primary microglial cell cultures. Moreover, we verified that not only indirect inhibition of Kmo using minocycline but also direct inhibition using Kmo inhibitors (JM6,Ro61-6048) decreased neuropathic pain intensity. Ro61-6048 administration reduced in the spinal cord and/or the DRG the protein levels of IBA-1, IL-6, IL-1beta and NOS2. Interestingly, Kmo inhibitors potentiated the analgesic properties of morphine. Summing up, our results suggest that the kynurenine pathway is an important mediator of neuropathic pain pathology. FINANCIAL SUPPORT: Supported by National Science Centre grant-Sonata 2015/17/D/NZ4/02284 and statutory funds. AP is a scholarship holder from the KNOW sponsored by Ministry of Science and Higher Education, Republic of Poland.

• Wydawca: -
• Czasopismo: Acta Neurobiologiae Experimentalis
• Rocznik: 2017
• Tom: 77
• Numer: Suppl.1
• Opis fizyczny: p.46-47

Twórcy

autor

Rojewska E.

• Institute of Pharmacology Polish Academy of Sciences, Department of Pain, Pharmacology, Cracow, Poland

autor

Piotrowska A.

• Institute of Pharmacology Polish Academy of Sciences, Department of Pain, Pharmacology, Cracow, Poland

autor

Jurga A.M.

• Institute of Pharmacology Polish Academy of Sciences, Department of Pain, Pharmacology, Cracow, Poland

autor

Makuch W.

• Institute of Pharmacology Polish Academy of Sciences, Department of Pain, Pharmacology, Cracow, Poland

autor

Przewlocka B.

• Institute of Pharmacology Polish Academy of Sciences, Department of Pain, Pharmacology, Cracow, Poland

autor

Mika J.

• Institute of Pharmacology Polish Academy of Sciences, Department of Pain, Pharmacology, Cracow, Poland