Flexibilide obtained from cultured soft coral has anti-neuroinflammatory and analgesic effects through the upregulation of spinal transforming growth factor-β1 in neuropathic rats.

Abstract

Chronic neuroinflammation plays an important role in the development and maintenance of neuropathic pain. The compound flexibilide, which can be obtained from cultured soft coral, possesses anti-inflammatory and analgesic effects in the rat carrageenan peripheral inflammation model. In the present study, we investigated the antinociceptive properties of flexibilide in the rat chronic constriction injury (CCI) model of neuropathic pain. First, we found that a single intrathecal (i.t.) administration of flexibilide significantly attenuated CCI-induced thermal hyperalgesia at 14 days after surgery. Second, i.t. administration of 10-μg flexibilide twice daily was able to prevent the development of thermal hyperalgesia and weight-bearing deficits in CCI rats. Third, i.t. flexibilide significantly inhibited CCI-induced activation of microglia and astrocytes, as well as the upregulated proinflammatory enzyme, inducible nitric oxide synthase, in the ipsilateral spinal dorsal horn. Furthermore, flexibilide attenuated the CCI-induced downregulation of spinal transforming growth factor-β1 (TGF-β1) at 14 days after surgery. Finally, i.t. SB431542, a selective inhibitor of TGF-β type I receptor, blocked the analgesic effects of flexibilide in CCI rats. Our results suggest that flexibilide may serve as a therapeutic agent for neuropathic pain. In addition, spinal TGF-β1 may be involved in the anti-neuroinflammatory and analgesic effects of flexibilide.

• Authors: Nan-Fu Chen, Shi-Ying Huang, Ching-Hsiang Lu, Chun-Lin Chen, Chien-Wei Feng, Chun-Hong Chen, Han-Chun Hung, Yen-You Lin, Ping-Jyun Sung, Chun-Sung Sung, San-Nan Yang, Hui-Min David Wang, Yu-Chia Chang, Jyh-Horng Sheu, Wu-Fu Chen, Zhi-Hong Wen
• Journal: Marine drugs (Mar Drugs) Vol. 12 Issue 7 Pg. 3792-817 (Jun 27 2014) ISSN: 1660-3397 [Electronic] Switzerland
• PMID: 24979268 (Publication Type: Journal Article, Research Support, Non-U.S. Gov't)

Chemical References

• Analgesics
• Anti-Inflammatory Agents
• Lactones
• Receptors, Transforming Growth Factor beta
• Transforming Growth Factor beta1
• flexibilide
• Protein Serine-Threonine Kinases
• Receptor, Transforming Growth Factor-beta Type I
• Tgfbr1 protein, rat

Topics

• Analgesics (pharmacology)
• Animals
• Anthozoa (metabolism)
• Anti-Inflammatory Agents (pharmacology)
• Hyperalgesia (drug therapy)
• Lactones (pharmacology)
• Male
• Neuralgia (drug therapy)
• Neuroglia (drug effects)
• Protein Serine-Threonine Kinases (antagonists & inhibitors)
• Rats
• Rats, Wistar
• Receptor, Transforming Growth Factor-beta Type I
• Receptors, Transforming Growth Factor beta (antagonists & inhibitors)
• Transforming Growth Factor beta1 (physiology)
• Up-Regulation