期刊
PAIN
卷 152, 期 9, 页码 2108-2116出版社
LIPPINCOTT WILLIAMS & WILKINS
DOI: 10.1016/j.pain.2011.05.018
关键词
Eugenol; HCN channels; I-h; Mechanical allodynia; Neuropathic pain; Thermal hyperalgesia
资金
- Ministry of Education, Science and Technology, the Republic of Korea [2008-0060065, 2009-0086663, 2010K000816, 2009-0077852]
- National Research Foundation of Korea [2009-0077852, 2009-0086663, 2008-0060065] Funding Source: Korea Institute of Science & Technology Information (KISTI), National Science & Technology Information Service (NTIS)
Mechanical allodynia is a common symptom found in neuropathic patients. Hyperpolarization-activated cyclic nucleotide-gated channels and their current, I-h, have been suggested to play an important role in neuropathic pain, especially in mechanical allodynia and spontaneous pain, by involvement in spontaneous ectopic discharges after peripheral nerve injury. Thus, I-h blockers may hold therapeutic potential for the intervention of mechanical allodynia under diverse neuropathic conditions. Here we show that eugenol blocks I-h and abolishes mechanical allodynia in the trigeminal system. Eugenol produced robust inhibition of I-h with IC50 of 157 mu M in trigeminal ganglion (TG) neurons, which is lower than the dose of eugenol that inhibits voltage-gated Na channels. Eugenol-induced I-h inhibition was not mediated by G(i/o)-protein activation, but was gradually diminished by an increase in intracellular cAMP concentration. Eugenol also inhibited I-h from injured TG neurons which were identified by retrograde labeling with DiI and reversed mechanical allodynia in the orofacial area after chronic constriction injury of infraorbital nerve. We propose that eugenol could be potentially useful for reversing mechanical allodynia in neuropathic pain patients. (C) 2011 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.
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