title: Eugenol reverses mechanical allodynia after peripheral nerve injury by inhibiting hyperpolarization-activated cyclic nucleotide-gated (HCN) channels.
abstract: 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 IC(50) of 157 μM 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.
authors.affiliation: National Research Laboratory for Pain, Dental Research Institute and Department of Neurobiology and Physiology, School of Dentistry, Seoul National University, Seoul 110-749, Republic of Korea Department of Oral Physiology and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea Department of Physiology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea.
authors.forename: Kyu-Yong
authors.initials: KY
authors.lastname: Yeon
authors.forename: Gehoon
authors.initials: G
authors.lastname: Chung
authors.forename: Yong Ho
authors.initials: YH
authors.lastname: Kim
authors.forename: Jae Hong
authors.initials: JH
authors.lastname: Hwang
authors.forename: Alexander J
authors.initials: AJ
authors.lastname: Davies
authors.forename: Min-Kyoung
authors.initials: MK
authors.lastname: Park
authors.forename: Dong Kuk
authors.initials: DK
authors.lastname: Ahn
authors.forename: Joong Soo
authors.initials: JS
authors.lastname: Kim
authors.forename: Sung Jun
authors.initials: SJ
authors.lastname: Jung
authors.forename: Seog Bae
authors.initials: SB
authors.lastname: Oh
mesh_terms: D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000818:Animals; D054815:Cyclic Nucleotide-Gated Cation Channels / Q000037:antagonists & inhibitors* / Q000502:physiology; D004305:Dose-Response Relationship, Drug; D005054:Eugenol / Q000494:pharmacology* / Q000627:therapeutic use*; D006930:Hyperalgesia / Q000188:drug therapy* / Q000503:physiopathology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D008297:Male; D015221:Potassium Channels / Q000502:physiology; D051381:Rats; D017207:Rats, Sprague-Dawley; D012668:Trigeminal Ganglion / Q000187:drug effects / Q000293:injuries* / Q000503:physiopathology
chemical_list: D054815:Cyclic Nucleotide-Gated Cation Channels; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D005054:Eugenol