Neuronal Hyperpolarization-Activated Pacemaker Channels Drive Neuropathic Pain

@article{Chaplan2003NeuronalHP,
 title={Neuronal Hyperpolarization-Activated Pacemaker Channels Drive Neuropathic Pain},
 author={Sandra R. Chaplan and Hong-Qing Guo and Doo Hyun Lee and Lin Luo and Changlu Liu and Chester Kuei and Alexander A. Velumian and Matthew P. Butler and Sean M. Brown and Adrienne E. Dubin},
 journal={The Journal of Neuroscience},
 year={2003},
 volume={23},
 pages={1169 - 1178},
 url={https://api.semanticscholar.org/CorpusID:8387253}
}
It is demonstrated that hyperpolarization-activated, cyclic nucleotide-modulated (HCN) "pacemaker" channels play a previously unrecognized role in both touch-related pain and spontaneous neuronal discharge originating in the damaged dorsal root ganglion.

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Peripheral Neuropathy Induces HCN Channel Dysfunction in Pyramidal Neurons of the Medial Prefrontal Cortex
Electrophysiological and behavioral results support an important role for hyperpolarization-activated cyclic nucleotide-gated channels and the cAMP/protein kinase A signaling axis in promoting hyperexcitability and persistent firing in pyramidal neurons of the mPFC in neuropathic animals.

HCN2 ion channels: basic science opens up possibilities for therapeutic intervention in neuropathic pain.
Data is reviewed demonstrating that the HCN2 isoform acts in an analogous way as a 'pacemaker for pain', in that its activity in nociceptive neurons is critical for the maintenance of electrical activity and for the sensation of chronic pain in pathological pain states.

K+ Channels in Primary Afferents and Their Role in Nerve Injury-Induced Pain
Evidence presently available points to a seminal role for interleukin 1β (IL-1β) in control of K+ channel function, and attempts to target K+ channels for therapeutic pain management have met with limited success.

Hyperpolarization-activated cyclic nucleotide–gated 2 (HCN2) ion channels drive pain in mouse models of diabetic neuropathy
It is proposed that the increased intracellular cAMP drives diabetes-associated pain by facilitating HCN2 activation and consequently promoting repetitive firing in primary nociceptive nerve fibers, suggesting that HCN 2 may be an analgesic target in the treatment of painful diabetic neuropathy.

HCN2 Ion Channels Play a Central Role in Inflammatory and Neuropathic Pain
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