Parthenolide Relieves Pain and Promotes M2 Microglia/Macrophage Polarization in Rat Model of Neuropathy.

Katarzyna Popiolek-Barczyk,Anna Piotrowska,Dominika Pilat,Ewelina Rojewska,Natalia Kolosowska,Joanna Mika,Agnieszka M Jurga,Wioletta Makuch

doi:10.1155/2015/676473

Katarzyna Popiolek-Barczyk, Anna Piotrowska + Show 6 more

Open Access

https://doi.org/10.1155/2015/676473

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Journal: Neural plasticity	Publication Date: Jan 1, 2015
Citations: 140	License type: CC BY 3.0

Affiliation: Maj Institute of Pharmacology

Abstract

Neuropathic pain treatment remains a challenge because pathomechanism is not fully understood. It is believed that glial activation and increased spinal nociceptive factors are crucial for neuropathy. We investigated the effect of parthenolide (PTL) on the chronic constriction injury to the sciatic nerve (CCI)-induced neuropathy in rat. We analyzed spinal changes in glial markers and M1 and M2 polarization factors, as well as intracellular signaling pathways. PTL (5 µg; i.t.) was preemptively and then daily administered for 7 days after CCI. PTL attenuated the allodynia and hyperalgesia and increased the protein level of IBA1 (a microglial/macrophage marker) but did not change GFAP (an astrocyte marker) on day 7 after CCI. PTL reduced the protein level of M1 (IL-1β, IL-18, and iNOS) and enhanced M2 (IL-10, TIMP1) factors. In addition, it downregulated the phosphorylated form of NF-κB, p38MAPK, and ERK1/2 protein level and upregulated STAT3. In primary microglial cell culture we have shown that IL-1β, IL-18, iNOS, IL-6, IL-10, and TIMP1 are of microglial origin. Summing up, PTL directly or indirectly attenuates neuropathy symptoms and promotes M2 microglia/macrophages polarization. We suggest that neuropathic pain therapies should be shifted from blanketed microglia/macrophage suppression toward maintenance of the balance between neuroprotective and neurotoxic microglia/macrophage phenotypes.

Highlights

Despite advances in medicine and the systematic introduction of new drugs, the available treatment for neuropathic pain is still not satisfactory [1,2,3]
Several studies indicate that microglia/macrophage activation is a polarized process, which results in cells with either pro- or antinociceptive properties; the regulation of this phenomenon is still unknown [9, 10]
In our work with microglial primary cell cultures [16] we reported that activated microglial cells are an important source of many nociceptive factors, like IL-1β, IL-6, IL-18, IL-1α, and IL-10

Summary

Introduction

Despite advances in medicine and the systematic introduction of new drugs, the available treatment for neuropathic pain is still not satisfactory [1,2,3]. There is a rapidly growing body of evidence indicating that signaling from microglia plays a relevant role in the pathogenesis of neuropathic pain [4,5,6,7,8]. The microglia rapidly became activated and mobilized to the site of injury where they initiate the release of effector molecules and recruitment of other immune cells. Several studies indicate that microglia/macrophage activation is a polarized process, which results in cells with either pro- or antinociceptive properties; the regulation of this phenomenon is still unknown [9, 10]. The M2 phase is associated with the release of markers, which are anti-inflammatory factors with antinociceptive properties, such as IL-10 and tissue inhibitor of metalloproteinases 1 (TIMP1) [12,13,14,15].

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