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Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice

Title
Antinociceptive curcuminoid, KMS4034, effects on inflammatory and neuropathic pain likely via modulating TRPV1 in mice
Author
정승준
Keywords
calcitonin gene-related peptide; curcuminoid synthesis; pain; inflammatory; neuropathic; TRPV1 receptor; nociceptive; GENE-RELATED PEPTIDE; SPINAL DORSAL-HORN; FORMALIN TEST; CAPSAICIN RECEPTOR; NERVE INJURY; SUBSTANCE-P; SENSORY NEURONS; RAT; MODEL; HYPERALGESIA
Issue Date
2013-10
Publisher
Oxford University Press
Citation
British Journal of Anaesthesia, 2013, 111(4), P.667-672
Abstract
Background. Curcumin, the active ingredient of turmeric (Curcuma longa), has a wide range of beneficial effects including anti-inflammation and analgesia. However, poor bioavailability of curcumin hinders its clinical application. To overcome this limitation, we modified the structure of curcumin and synthesized new derivatives with favourable pharmacokinetic profiles. Recently, curcumin has been shown to have an antagonizing effect on transient receptor potential vanilloid type 1 (TRPV1) ion channels. We investigated the antinociceptive activity of KMS4034 which had the most favourable pharmacokinetics among the tested curcumin derivatives.Methods. To evaluate the mechanism of the antinociceptive effects of KMS4034, capsaicin (I-cAp)- and heat (I-heat)-induced currents in TRPV1 expressing HEK293 cells were observed after the application of KMS4034. Nociceptive behavioural measurement using the hot-plate test, formalin test, and chronic constriction injury (CCI) model were evaluated in mice. Also, calcitonin gene-related peptide (CGRP) was stained immunohistochemically in the L4/5 dorsal horns in mice with neuropathic pain.Results. I-CAP, (P<0.01) and I-heat (P<0.05) of TRPV1 were significantly blocked by 10 mu M KMS4034. Behaviourally, noticeable antinociceptive effects after 10 mg kg(-1) of KMS4034 treatment were observed in the first (P<0.05) and second phases (P<0.05) of the formalin and hot-plate tests. The mechanical threshold of CCI mice treated with 10 mg kg(-1) KMS4034 was significantly increased compared with control. Immunohistochemical CGRP expression was decreased in the lamina I-II of the lumbar dorsal horns in KMS4034-treated CCI mice compared with the control (P<0.05).Conclusions. KMS4034 may be an effective analgesic for various pain conditions.
URI
http://bjanaesthesia.org/article/S0007-0912(17)32363-2/abstracthttp://hdl.handle.net/20.500.11754/44539
ISSN
0007-0912; 1471-6771
DOI
10.1093/bja/aet176
Appears in Collections:
COLLEGE OF MEDICINE[S](의과대학) > MEDICINE(의학과) > Articles
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