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Biomaterials. 2015 Jun;53:1-11. doi: 10.1016/j.biomaterials.2015.02.069. Epub 2015 Mar 7.

The use of the antimicrobial peptide piscidin (PCD)-1 as a novel anti-nociceptive agent.

Author information

1
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.
2
Center for Neuroscience, National Sun Yat-Sen University, 70 Lien-Hai Rd, Kaohsiung 804, Taiwan.
3
Department of Marine Biotechnology and Resources, National Sun Yat-Sen University, 70 Lien-Hai Rd, Kaohsiung 804, Taiwan.
4
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.
5
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.
6
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.

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.

KEYWORDS:

Allodynia; Antimicrobial peptide; Chronic constriction injury; Hyperalgesia; Neuropathic pain; Piscidin-1

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