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The role of HCN channels within the periaqueductal gray in neuropathic pain.
Brain Res. 2013 Mar 15; 1500:36-44.BR

Abstract

Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a key role in neuropathic pain by regulating neuronal excitability. HCN channels are expressed in the ventral-lateral periaqueductal gray (vlPAG), a region that is important for pain modulation. However, the role of vlPAG HCN channels in neuropathic pain remains poorly understood. In the present study, we investigated the impact of changes to vlPAG HCN channels on neural activity in neuropathic pain. First, sciatic nerve chronic constriction injury (CCI) was established as a neuropathic pain model. Then, changes in HCN channels and their influence on vlPAG neuronal activity were detected. Our results indicate that after CCI surgery the following changes occur in vlPAG neurons: the expression of HCN1 and HCN2 channels is increased, the amplitude of the hyperpolarization-activated current (Ih) is augmented and its activation curve is shifted to more positive potentials and there is an increase in the frequency of action potential (AP) firing and spontaneous EPSCs that is attenuated by ZD7288, a HCN channel blocker. In addition, forskolin, which can elevate intracellular cAMP, mimics the CCI induced changes in neuronal excitability in the vlPAG. The effects of forskolin were also reversed by ZD7288. Taken together, the present data indicate an important role for HCN channels in the vlPAG in neuropathic pain.

Authors+Show Affiliations

Department of Neurobiology, College of Basic Medical Sciences, Chongqing Key Laboratory of Neurobiology, Third Military Medical University, Chongqing 400038, China.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

23375842

Citation

Du, Lu, et al. "The Role of HCN Channels Within the Periaqueductal Gray in Neuropathic Pain." Brain Research, vol. 1500, 2013, pp. 36-44.
Du L, Wang SJ, Cui J, et al. The role of HCN channels within the periaqueductal gray in neuropathic pain. Brain Res. 2013;1500:36-44.
Du, L., Wang, S. J., Cui, J., He, W. J., & Ruan, H. Z. (2013). The role of HCN channels within the periaqueductal gray in neuropathic pain. Brain Research, 1500, 36-44. https://doi.org/10.1016/j.brainres.2013.01.035
Du L, et al. The Role of HCN Channels Within the Periaqueductal Gray in Neuropathic Pain. Brain Res. 2013 Mar 15;1500:36-44. PubMed PMID: 23375842.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The role of HCN channels within the periaqueductal gray in neuropathic pain. AU - Du,Lu, AU - Wang,Shao-Jun, AU - Cui,Jian, AU - He,Wen-Juan, AU - Ruan,Huai-Zhen, Y1 - 2013/01/31/ PY - 2012/09/17/received PY - 2013/01/19/revised PY - 2013/01/21/accepted PY - 2013/2/5/entrez PY - 2013/2/5/pubmed PY - 2013/8/16/medline SP - 36 EP - 44 JF - Brain research JO - Brain Res VL - 1500 N2 - Peripheral and spinal hyperpolarization-activated cyclic nucleotide-gated (HCN) channels play a key role in neuropathic pain by regulating neuronal excitability. HCN channels are expressed in the ventral-lateral periaqueductal gray (vlPAG), a region that is important for pain modulation. However, the role of vlPAG HCN channels in neuropathic pain remains poorly understood. In the present study, we investigated the impact of changes to vlPAG HCN channels on neural activity in neuropathic pain. First, sciatic nerve chronic constriction injury (CCI) was established as a neuropathic pain model. Then, changes in HCN channels and their influence on vlPAG neuronal activity were detected. Our results indicate that after CCI surgery the following changes occur in vlPAG neurons: the expression of HCN1 and HCN2 channels is increased, the amplitude of the hyperpolarization-activated current (Ih) is augmented and its activation curve is shifted to more positive potentials and there is an increase in the frequency of action potential (AP) firing and spontaneous EPSCs that is attenuated by ZD7288, a HCN channel blocker. In addition, forskolin, which can elevate intracellular cAMP, mimics the CCI induced changes in neuronal excitability in the vlPAG. The effects of forskolin were also reversed by ZD7288. Taken together, the present data indicate an important role for HCN channels in the vlPAG in neuropathic pain. SN - 1872-6240 UR - https://www.unboundmedicine.com/medline/citation/23375842/The_role_of_HCN_channels_within_the_periaqueductal_gray_in_neuropathic_pain_ L2 - https://linkinghub.elsevier.com/retrieve/pii/S0006-8993(13)00131-5 DB - PRIME DP - Unbound Medicine ER -