Plasticity of hyperpolarization-activated and cyclic nucleotid-gated cation channel subunit 2 expression in the spinal dorsal horn in inflammatory pain.

A great deal of experimental evidence has already been accumulated that hyperpolarization-activated and cyclic nucleotide-gated cation channels (HCN) expressed by peripheral nerve fibers contribute to the initiation of nerve activities leading to pain. Complementing these findings, we have recently demonstrated that HCN subunit 2 (HCN2) channel protein is also widely expressed by axon terminals of substance P (SP)-containing peptidergic nociceptive primary afferents in laminae I-IIo of the spinal dorsal horn, and postulated that they may play a role in spinal pain processing. In the present study, we investigated how the expression of HCN2 ion channels in the spinal dorsal horn may change in inflammatory pain evoked by unilateral injection of complete Freund's adjuvant (CFA) into the hind paw of rats. We found that 3 days after CFA injection, when the nociceptive responsiveness of the inflamed hind paw had substantially increased, the numbers of HCN2-immunolabeled axon terminals were also significantly augmented in laminae I-IIo of the spinal dorsal horn ipsilateral to the site of CFA injection. The elevation of HCN2 immunoreactivity was paralleled by an increase in SP immunoreactivity. In addition, similarly to control animals, the co-localization between HCN2 and SP immunoreactivity was remarkably high, suggesting that central axon terminals of nociceptive primary afferents that increased their SP expression in response to CFA injection into the hind paw also increased their HCN2 expression. The results indicate that HCN2 ion channel mechanisms may play a role in SP-mediated spinal pain processing not only in naive animals but also in chronic inflammatory pain.

Papp I ，Holló K ，Antal M 《-》

Expression of hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 in axon terminals of peptidergic nociceptive primary sensory neurons in the superficial spinal dorsal horn of rats.

Antal M ，Papp I ，Bahaerguli N ，Veress G ，Vereb G ... -  《EUROPEAN JOURNAL OF NEUROSCIENCE》

Hyperpolarization-activated and cyclic nucleotide-gated cation channel subunit 2 ion channels modulate synaptic transmission from nociceptive primary afferents containing substance P to secondary sensory neurons in laminae I-IIo of the rodent spinal dorsa

Papp I ，Szucs P ，Holló K ，Erdélyi F ，Szabó G ，Antal M ... -  《EUROPEAN JOURNAL OF NEUROSCIENCE》

Reduced potassium-chloride co-transporter expression in spinal cord dorsal horn neurons contributes to inflammatory pain hypersensitivity in rats.

Zhang W ，Liu LY ，Xu TL 《NEUROSCIENCE》

Effect of chronic inflammation on dorsal horn nociceptive neurons in aged rats.

Kitagawa J ，Kanda K ，Sugiura M ，Tsuboi Y ，Ogawa A ，Shimizu K ，Koyama N ，Kamo H ，Watanabe T ，Ren K ，Iwata K ... -  《JOURNAL OF NEUROPHYSIOLOGY》