Eugenol reverses mechanical allodynia at relatively lower concentrations than that which effectively blocks thermal hyperalgesia in the trigeminal system, acting via the inhibition of Ih currents.
Mechanical allodynia is a common symptom found in neuropathic patients. Hyperpolarization-activated cyclic nucleotide-gated channels and their current, Ih, 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, Ih blockers may hold therapeutic potential for the intervention of mechanical allodynia under diverse neuropathic conditions. Here we show that eugenol blocks Ih and abolishes mechanical allodynia in the trigeminal system. Eugenol produced robust inhibition of Ih with IC50 of 157 μM in trigeminal ganglion (TG) neurons, which is lower than the dose of eugenol that inhibits voltage-gated Na channels. Eugenol-induced Ih inhibition was not mediated by Gi/o-protein activation, but was gradually diminished by an increase in intracellular cAMP concentration. Eugenol also inhibited Ih 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.
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
aNational 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
bDepartment of Oral Physiology and Neurobiology, School of Dentistry, Kyungpook National University, Daegu 700-412, Republic of Korea
cDepartment of Physiology, College of Medicine, Hanyang University, Seoul 133-791, Republic of Korea
*Corresponding authors. Tel.: +82 2 740 8656; fax: +82 2 762 5107 (S.B. Oh), tel./fax: +82 2 2220 0612 (S.J. Jung).
1These authors contributed equally to this work.
Article history: Received 24 December 2010; Received in revised form 28 April 2011; Accepted 17 May 2011.