title: Neuropeptide S modulates the amygdaloidal HCN activities (Ih) in rats: Implication in chronic pain.
abstract: Neuropeptide S (NPS), an endogenous anxiolytic, has been shown to protect against chronic pain through interacting with its cognate NPS receptor (NPSR) in the brain. However, the cellular mechanism of this NPS action remains unclear. We report that NPS inhibits hyperpolarization-activated cyclic nucleotide-gated (HCN) channel current (Ih) in the rat's amygdala through activation of NPSR. This NPS effect is mediated through ERK1/2 phosphorylation in a subset of pyramidal-like neurons located in the medial amygdala. The characters of the recorded Ih suggest a major role for HCN1 activity in this process. Inhibition of Ih by NPS stimulates the glutamatergic drive onto fast spiking intra-amygdalolidal GABAergic interneurons, which in turn facilitates GABA release onto pyramidal-like neurons. Moreover, the HCN1 expression is increased in the amygdala of rats with peripheral nerve injury and intra-amygdaloidal administration of the HCN channel inhibitor ZD7288 attenuates nociceptive behavior in these rats. These results suggest that NPS-mediated modulation of intra-amygdaloidal HCN channel activities may be an important central inhibitory mechanism for regulation of chronic pain.
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA; Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing, 100850, China.
authors: Shuzhuo
authors: S
authors: Zhang
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Zerong
authors: Z
authors: You
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Shuxing
authors: S
authors: Wang
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Jinsheng
authors: J
authors: Yang
authors: Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing, 100850, China.
authors: Lujia
authors: L
authors: Yang
authors: Beijing Institute of Pharmacology and Toxicology, 27 Tai-Ping Road, Beijing, 100850, China.
authors: Yan
authors: Y
authors: Sun
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Wenli
authors: W
authors: Mi
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Liling
authors: L
authors: Yang
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Michael F
authors: MF
authors: McCabe
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Shiqian
authors: S
authors: Shen
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA.
authors: Lucy
authors: L
authors: Chen
authors: MGH Center for Translational Pain Research, Department of Anesthesia, Critical Care and Pain Medicine, Massachusetts General Hospital, Harvard Medical School, Boston, MA 02114, USA. Electronic address: jmao@mgh.harvard.edu.
authors: Jianren
authors: J
authors: Mao
mesh_terms: D000679:Amygdala / Q000187:drug effects*; D000818:Animals; D059350:Chronic Pain / Q000188:drug therapy*; D018698:Glutamic Acid / Q000378:metabolism; D006930:Hyperalgesia / Q000188:drug therapy; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels / Q000037:antagonists & inhibitors / Q000187:drug effects*; D007395:Interneurons / Q000187:drug effects / Q000378:metabolism; D020935:MAP Kinase Signaling System; D008297:Male; D009479:Neuropeptides / Q000494:pharmacology*; D018408:Patch-Clamp Techniques; D015221:Potassium Channels / Q000187:drug effects*; D017966:Pyramidal Cells / Q000187:drug effects; D011743:Pyrimidines / Q000494:pharmacology; D051381:Rats; D017207:Rats, Sprague-Dawley; D015320:Tachykinins; D005680:gamma-Aminobutyric Acid / Q000378:metabolism / Q000502:physiology
chemical_list: C578667:Hcn1 protein, rat; D064428:Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; D009479:Neuropeptides; D015221:Potassium Channels; D011743:Pyrimidines; D015320:Tachykinins; C569868:neuropeptide S precursor protein, human; C534458:neuropeptide S, rat; C082246:ICI D2788; D018698:Glutamic Acid; D005680:gamma-Aminobutyric Acid
keywords: Amygdala; GABA; HCN; NPS; Pain