Preventive Effects of Bee Venom Derived Phospholipase A₂ on Oxaliplatin-Induced Neuropathic Pain in Mice.

Abstract

Oxaliplatin, a chemotherapy drug used to treat colorectal cancer, induces specific sensory neurotoxicity signs that are aggravated by cold and mechanical stimuli. Here we examined the preventive effects of Bee Venom (BV) derived phospholipase A₂ (bvPLA₂) on oxaliplatin-induced neuropathic pain in mice and its immunological mechanism. The cold and mechanical allodynia signs were evaluated by acetone and von Frey hair test on the hind paw, respectively. The most significant allodynia signs were observed at three days after an injection of oxaliplatin (6 mg/kg, i.p.) and then decreased gradually to a normal level on days 7-9. The oxaliplatin injection also induced infiltration of macrophages and upregulated levels of the pro-inflammatory cytokine interleukin (IL)-1β in the lumbar dorsal root ganglia (DRG). Daily treatment with bvPLA₂ (0.2 mg/kg, i.p.) for five consecutive days prior to the oxaliplatin injection markedly inhibited the development of cold and mechanical allodynia, and suppressed infiltration of macrophages and the increase of IL-1β level in the DRG. Such preventive effects of bvPLA₂ were completely blocked by depleting regulatory T cells (Tregs) with CD25 antibody pre-treatments. These results suggest that bvPLA₂ may prevent oxaliplatin-induced neuropathic pain by suppressing immune responses in the DRG by Tregs.

• Authors: Dongxing Li, Woojin Kim, Dasom Shin, Yongjae Jung, Hyunsu Bae, Sun Kwang Kim
• Journal: Toxins (Toxins (Basel)) Vol. 8 Issue 1 (Jan 19 2016) ISSN: 2072-6651 [Electronic] Switzerland
• PMID: 26797636 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Bee Venoms
• Interleukin-1beta
• Organoplatinum Compounds
• Tumor Necrosis Factor-alpha
• Oxaliplatin
• Phospholipases A2

Topics

• Analgesics (pharmacology, therapeutic use)
• Animals
• Bee Venoms (chemistry)
• Cold Temperature
• Ganglia, Spinal (drug effects, immunology)
• Hyperalgesia (chemically induced, drug therapy, immunology)
• Interleukin-1beta (immunology)
• Macrophages (drug effects, immunology)
• Male
• Mice, Inbred C57BL
• Mice, Transgenic
• Neuralgia (chemically induced, drug therapy, immunology)
• Organoplatinum Compounds
• Oxaliplatin
• Phospholipases A2 (pharmacology, therapeutic use)
• T-Lymphocytes, Regulatory (immunology)
• Tumor Necrosis Factor-alpha (immunology)