title: 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: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. chen06688@gmail.com.
authors: Nan-Fu
authors: NF
authors: Chen
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. johnjohnkings@gmail.com.
authors: Shi-Ying
authors: SY
authors: Huang
authors: Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan. alfaleu@gmail.com.
authors: Ching-Hsiang
authors: CH
authors: Lu
authors: Division of Neurosurgery, Department of Surgery, Kaohsiung Armed Forces General Hospital, Kaohsiung 80284, Taiwan. springwei@hotmail.com.tw.
authors: Chun-Lin
authors: CL
authors: Chen
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. jay0404@gmail.com.
authors: Chien-Wei
authors: CW
authors: Feng
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. jay0404@gmail.com.
authors: Chun-Hong
authors: CH
authors: Chen
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. jay0404@gmail.com.
authors: Han-Chun
authors: HC
authors: Hung
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. chas6119@gmail.com.
authors: Yen-You
authors: YY
authors: Lin
authors: National Museum of Marine Biology and Aquarium, Pingtung 944, Taiwan. pjsung@nmmba.gov.tw.
authors: Ping-Jyun
authors: PJ
authors: Sung
authors: Department of Anesthesiology, Taipei Veterans General Hospital, Taipei 11217, Taiwan. cssung@vghtpe.gov.tw.
authors: Chun-Sung
authors: CS
authors: Sung
authors: School of Medicine, College of Medicine and Department of Pediatrics, E-DA Hospital, I-Shou University, Kaohsiung 84001, Taiwan. y520729@gmail.com.
authors: San-Nan
authors: SN
authors: Yang
authors: Department of Fragrance and Cosmetic Science, Kaohsiung Medical University, Kaohsiung 80708, Taiwan. davidw@kmu.edu.tw.
authors: Hui-Min David
authors: HM
authors: Wang
authors: Doctoral Degree Program in Marine Biotechnology, National Sun Yat-sen University and Academia Sinica, Kaohsiung 80424, Taiwan. jay0404@gmail.com.
authors: Yu-Chia
authors: YC
authors: Chang
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. jay0404@gmail.com.
authors: Jyh-Horng
authors: JH
authors: Sheu
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. ma4949@cgmh.org.tw.
authors: Wu-Fu
authors: WF
authors: Chen
authors: Department of Marine Biotechnology and Resources, Asia-Pacific Ocean Research Center, National Sun Yat-sen University, Kaohsiung 80424, Taiwan. wzh@mail.nsysu.edu.tw.
authors: Zhi-Hong
authors: ZH
authors: Wen
mesh_terms: D000700:Analgesics / Q000494:pharmacology*; D000818:Animals; D037421:Anthozoa / Q000378:metabolism*; D000893:Anti-Inflammatory Agents / Q000494:pharmacology*; D006930:Hyperalgesia / Q000188:drug therapy; D007783:Lactones / Q000494:pharmacology*; D008297:Male; D009437:Neuralgia / Q000188:drug therapy*; D009457:Neuroglia / Q000187:drug effects; D017346:Protein Serine-Threonine Kinases / Q000037:antagonists & inhibitors; D051381:Rats; D017208:Rats, Wistar; D000077293:Receptor, Transforming Growth Factor-beta Type I; D018125:Receptors, Transforming Growth Factor beta / Q000037:antagonists & inhibitors; D053773:Transforming Growth Factor beta1 / Q000502:physiology*; D015854:Up-Regulation
chemical_list: D000700:Analgesics; D000893:Anti-Inflammatory Agents; D007783:Lactones; D018125:Receptors, Transforming Growth Factor beta; D053773:Transforming Growth Factor beta1; C027469:flexibilide; D017346:Protein Serine-Threonine Kinases; D000077293:Receptor, Transforming Growth Factor-beta Type I; C000625843:Tgfbr1 protein, rat