title: The use of the antimicrobial peptide piscidin (PCD)-1 as a novel anti-nociceptive agent.
abstract: The antimicrobial peptide piscidin (PCD)-1 has been reported to have antibacterial and immunomodulatory functions. Here, we investigated the anti-neuropathic properties of PCD-1, in order to determine its potential as a compound to alleviate pain. Treatment with PCD-1 suppressed the inflammatory proteins COX-2 and iNOS in murine macrophage (RAW264.7) and microglial (BV2) cell lines stimulated by lipopolysaccharide (LPS). For studies of the effect of PCD-1 in vivo, mononeuropathy in rats was induced by chronic constriction injury (CCI), and the resulting anti-nociceptive behaviors were compared between CCI controls and CCI rats given intrathecal injections of PCD-1. Much like gabapentin, PCD-1 exerts anti-nociceptive effects against thermal hyperalgesia, with a median effective dose (ED50) of 9.5 μg in CCI rats. In CCI rats, PCD-1 exerted effects against mechanical and cold allodynia, thermal hyperalgesia, and weight-bearing deficits. Furthermore, CCI-mediated activation of microglia and astrocytes in the dorsal horn of the lumbar spinal cord were decreased by PCD-1. In addition, PCD-1 suppressed up-regulation of interleukin-1β (IL-1β) and phosphorylated mammalian target of rapamycin (phospho-mTOR) in CCI rats. Finally, CCI-induced down-regulation of transforming growth factor-β1 (TGF-β1) in rats was attenuated by injection of PCD-1. Taken together, the present findings demonstrate that the marine antimicrobial peptide PCD-1 has anti-nociceptive effects, and thus may have potential for development as an alternative pain-alleviating agent.
authors.affiliation: Department of Neurosurgery, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Rd, Kaohsiung 833, Taiwan; Center for Parkinson's Disease, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, 123 Ta Pei Rd, Kaohsiung 833, Taiwan.
authors.forename: Wu-Fu
authors.initials: WF
authors.lastname: Chen
authors.affiliation: Center for Neuroscience, National Sun Yat-Sen University, 70 Lien-Hai Rd, Kaohsiung 804, Taiwan.
authors.forename: Shi-Ying
authors.initials: SY
authors.lastname: Huang
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Rd, Kaohsiung 804, Taiwan.
authors.forename: Chang-Yi
authors.initials: CY
authors.lastname: Liao
authors.affiliation: Department of Anesthesiology, Taipei Veterans General Hospital, 201 Sec 2, Shih-Pai Rd, Taipei 112, Taiwan; School of Medicine, National Yang-Ming University, 155 Sec 2, Li-Nong St, Taipei 112, Taiwan.
authors.forename: Chun-Sung
authors.initials: CS
authors.lastname: Sung
authors.affiliation: Marine Research Station, Institute of Cellular and Organismic Biology, Academia Sinica, 23-10 Dahuen Rd, Jiaushi, Ilan 262, Taiwan. Electronic address: zoocjy@gate.sinica.edu.tw.
authors.forename: Jyh-Yih
authors.initials: JY
authors.lastname: Chen
authors.affiliation: Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Rd, Kaohsiung 804, Taiwan; Marine Biomedical Laboratory and Center for Translational Biopharmaceuticals, Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Rd, Kaohsiung 804, Taiwan. Electronic address: wzh@mail.nsysu.edu.tw.
authors.forename: Zhi-Hong
authors.initials: ZH
authors.lastname: Wen
mesh_terms: D000595:Amino Acid Sequence; D000700:Analgesics / Q000627:therapeutic use*; D000818:Animals; D023181:Antimicrobial Cationic Peptides / Q000737:chemistry / Q000494:pharmacology*; D001253:Astrocytes / Q000187:drug effects; D002460:Cell Line; D051546:Cyclooxygenase 2 / Q000378:metabolism; D029941:Fish Proteins / Q000737:chemistry / Q000494:pharmacology*; D053583:Interleukin-1beta / Q000378:metabolism; D008297:Male; D051379:Mice; D017628:Microglia / Q000187:drug effects; D008969:Molecular Sequence Data; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D058570:TOR Serine-Threonine Kinases / Q000378:metabolism; D053773:Transforming Growth Factor beta1 / Q000378:metabolism; D015854:Up-Regulation / Q000187:drug effects
chemical_list: D000700:Analgesics; D023181:Antimicrobial Cationic Peptides; D029941:Fish Proteins; D053583:Interleukin-1beta; D053773:Transforming Growth Factor beta1; C449802:moronecidin protein, Morone saxatilis; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D058570:TOR Serine-Threonine Kinases
keywords: Allodynia; Antimicrobial peptide; Chronic constriction injury; Hyperalgesia; Neuropathic pain; Piscidin-1