Ulinastatin attenuates neuropathic pain induced by L5-VRT via the calcineurin/IL-10 pathway.

Abstract

Previous studies have shown that ulinastatin, an effective inhibitor of the inflammatory response in clinical applications, can attenuate hyperalgesia in rodents. However, the underlying mechanism remains unclear. In the present study, we first examined the change in the calcineurin level, which plays an important role in regulating cytokine release in the nervous system, following lumbar 5 ventral root transection in the rat. Furthermore, we determined whether intraperitoneal (i.p.) injection of ulinastatin attenuated pain behavior via inhibition of the calcineurin-mediated inflammatory response induced by lumbar 5 ventral root transection. The results showed that the paw withdrawal threshold and paw withdrawal latency were significantly decreased following lumbar 5 ventral root transection compared to the sham group. Neuropathic pain induced by lumbar 5 ventral root transection significantly decreased the expression of calcineurin in the DRG, and calcineurin was mostly located with NF-200-positive cells, IB4-positive cells, and CGRP-positive cells and less with GFAP-positive satellite cells. Furthermore, intrathecal (i.t.) injection of exogenous calcineurin attenuated the pain behavior induced by lumbar 5 ventral root transection. Importantly, intraperitoneal injection of ulinastatin alleviated the pain behavior and calcineurin downregulation induced by lumbar 5 ventral root transection. Lastly, the cytokine IL-10 was significantly decreased following lumbar 5 ventral root transection, and application of calcineurin (intrathecal) or ulinastatin (intraperitoneal) inhibited the IL-10 downregulation induced by lumbar 5 ventral root transection. These results suggested that ulinastatin, by acting on the CN/IL-10 pathway, might be a novel and effective drug for the treatment of neuropathic pain.

• Authors: Handong Ouyang, Bilin Nie, Peizong Wang, Qiang Li, Wan Huang, Wenjun Xin, Weian Zeng, Xianguo Liu
• Journal: Molecular pain (Mol Pain) Vol. 12 ( 2016) ISSN: 1744-8069 [Electronic] United States
• PMID: 27175013 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)
• Copyright: © The Author(s) 2016.

Chemical References

• Glycoproteins
• Interleukin-10
• Calcineurin
• urinastatin

Topics

• Animals
• Calcineurin (metabolism)
• Ganglia, Spinal (drug effects, metabolism, pathology)
• Glycoproteins (administration & dosage, pharmacology, therapeutic use)
• Injections, Intraperitoneal
• Injections, Spinal
• Interleukin-10 (metabolism)
• Lumbar Vertebrae (drug effects, injuries)
• Male
• Neuralgia (drug therapy, etiology, pathology)
• Rats, Sprague-Dawley
• Reaction Time (drug effects)
• Signal Transduction (drug effects)
• Spinal Nerve Roots (drug effects, injuries)