title: Inhibition of HCN channel activity in the thalamus attenuates chronic pain in rats.
abstract: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels regulate neuronal excitability in both peripheral and central nerve systems. Emerging evidence indicates that HCN channels are involved in the development and maintenance of chronic pain. However, the impact of HCN channel activity in the thalamus on chronic pain has not been examined. In this report, we evaluated the effect on nociceptive behaviors after infusion of a HCN channel blocker ZD7288 into the ventral posterolateral (VPL) nucleus of the thalamus in rats with neuropathic pain or monoarthritis. We show that ZD7288 dose-dependently attenuated mechanical allodynia and thermal hyperalgesia in rats with chronic pain. In the thalamus, immunoreactivity of both HCN1 and HCN2 subunits was increased in both rat models. These results suggest that the increased HCN channel activity in the thalamus of the ascending nociceptive pathway contributes to both chronic neuropathic and inflammatory pain conditions.
authors.affiliation: MGH Center for Translational Pain Research Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital Harvard Medical School Boston, MA, 02114, United States; The First Affiliated Hospital of Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China; Hangzhou First People's Hospital, 261 Huanshan Road, Hangzhou, 310006, China.
authors.forename: Weihua
authors.initials: W
authors.lastname: Ding
authors.affiliation: MGH Center for Translational Pain Research Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital Harvard Medical School Boston, MA, 02114, United States.
authors.forename: Zerong
authors.initials: Z
authors.lastname: You
authors.affiliation: MGH Center for Translational Pain Research Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital Harvard Medical School Boston, MA, 02114, United States.
authors.forename: Shiqian
authors.initials: S
authors.lastname: Shen
authors.affiliation: MGH Center for Translational Pain Research Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital Harvard Medical School Boston, MA, 02114, United States.
authors.forename: Lucy
authors.initials: L
authors.lastname: Chen
authors.affiliation: The First Affiliated Hospital of Zhejiang University, 79 Qingchun Road, Hangzhou, 310003, China. Electronic address: smzhu20088@163.com.
authors.forename: Shengmei
authors.initials: S
authors.lastname: Zhu
authors.affiliation: MGH Center for Translational Pain Research Department of Anesthesia, Critical Care and Pain Medicine Massachusetts General Hospital Harvard Medical School Boston, MA, 02114, United States. Electronic address: jmao@mgh.harvard.edu.
authors.forename: Jianren
authors.initials: J
authors.lastname: Mao
mesh_terms: D000818:Animals; D001169:Arthritis, Experimental / Q000503:physiopathology; D059350:Chronic Pain / Q000503:physiopathology*; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000503:physiopathology; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000378:metabolism / Q000502:physiology*; D008297:Male; D009437:Neuralgia / Q000503:physiopathology; D059225:Nociception / Q000502:physiology*; D015221:Potassium Channels / Q000378:metabolism / Q000502:physiology*; D011743:Pyrimidines / Q000008:administration & dosage; D051381:Rats; D017207:Rats, Sprague-Dawley; D013788:Thalamus / Q000378:metabolism / Q000503:physiopathology*
chemical_list: C578667:Hcn1 protein, rat; C578712:Hcn2 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D015221:Potassium Channels; D011743:Pyrimidines; C082246:ICI D2788; D005620:Freund's Adjuvant
keywords: HCN channel; Monoarthritis; Neuropathic pain; Thalamus; ZD7288