title: Plasticity of hyperpolarization-activated and cyclic nucleotid-gated cation channel subunit 2 expression in the spinal dorsal horn in inflammatory pain.
abstract: 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.
authors: Department of Anatomy, Histology and Embryology, Faculty of Medicine, Medical and Health Science Center, University of Debrecen, Nagyerdei krt. 98, 4032 Debrecen, Hungary.
authors: Ildikó
authors: I
authors: Papp
authors: Krisztina
authors: K
authors: Holló
authors: Miklós
authors: M
authors: Antal
mesh_terms: D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D004195:Disease Models, Animal; D005620:Freund's Adjuvant / Q000009:adverse effects; D007839:Functional Laterality; D005786:Gene Expression Regulation / Q000187:drug effects / Q000502:physiology*; D006930:Hyperalgesia / Q000209:etiology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D066298:In Vitro Techniques; D007249:Inflammation / Q000139:chemically induced / Q000150:complications*; D007473:Ion Channels / Q000235:genetics / Q000378:metabolism*; D008297:Male; D018613:Microscopy, Confocal; D010146:Pain / Q000209:etiology / Q000473:pathology*; D010147:Pain Measurement; D020671:Posterior Horn Cells / Q000187:drug effects / Q000378:metabolism* / Q000473:pathology; D015221:Potassium Channels; D017729:Presynaptic Terminals / Q000378:metabolism; D051381:Rats; D011921:Rats, Inbred WKY; D013116:Spinal Cord / Q000473:pathology*; D013373:Substance P / Q000378:metabolism
chemical_list: C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D007473:Ion Channels; D015221:Potassium Channels; D013373:Substance P; D005620:Freund's Adjuvant