Highlights
- •Infraorbital nerve injury (dIoN-CCI) induced trigeminal neuropathic pain (TNP).
- •HCN1 and HCN2 were the major HCN isoforms in the gasserian ganglion (GG).
- •Inhibition of HCN channel activity in the GG ameliorated TNP.
- •HCN blocker ivabradine showed a prolonged analgesic effect.
- •HCN1 and HCN2 expression was increased in the GG after dIoN-CCI.
Abstract
Orofacial neuropathic pain caused by trigeminal nerve injury is a debilitating condition
with limited therapeutic options. Hyperpolarization-activated cyclic nucleotide-gated
(HCN) channels regulate neuronal excitability and are involved in the development
and maintenance of chronic pain. However, the effect of HCN channel activity in the
Gasserian ganglion on trigeminal neuropathic pain has not been examined. We evaluated
nociceptive behaviors after microinjection of the HCN channel blockers ZD7288 or ivabradine
into the Gasserian ganglion in rats with trigeminal nerve injury. Both blockers dose-dependently
ameliorated evoked and spontaneous nociceptive behavior in rats with trigeminal neuropathic
pain. Moreover, the clinically available HCN channel blocker ivabradine showed a prolonged
antinociceptive effect. In the Gasserian ganglion, HCN1 and HCN2 are major HCN isoforms.
After trigeminal nerve injury, the counts of HCN1 as well as HCN2 immuno-positive
punctae were increased in the ipsilateral Gasserian ganglions. These results indicate
that the increased HCN channel activity in the Gasserian ganglion directly contributes
to neuropathic pain resulting from trigeminal nerve injury.
Perspective
Trigeminal nerve damage-induced orofacial pain is severe and more resistant to standard
pharmacological treatment than other types of neuropathic pain. Our study suggests
that targeting HCN channel activities in the Gasserian ganglion may provide an alternative
treatment of trigeminal neuropathy including trigeminal neuralgia.
Key words
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Article info
Publication history
Published online: January 21, 2018
Accepted:
January 3,
2018
Received in revised form:
December 15,
2017
Received:
September 28,
2017
Footnotes
W.D., Z.Y., and S.S. contributed equally to this work.
This work was supported by National Institutes of Health grants R01 DE022901 and R01 DE018214 (J.M.) and National Natural Science Foundation of China 81771194 (S.Z.).
The authors have no conflicts of interest to declare.
Identification
Copyright
© 2018 by the American Pain Society
