Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model

Richards, N and Dilley, A (2015) Contribution of hyperpolarization-activated channels to heat hypersensitivity and ongoing activity in the neuritis model. Neuroscience, 284. pp. 87-98. ISSN 0306-4522

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Abstract

Neuritis can cause pain hypersensitivities in the absence of axonal degeneration. Such hypersensitivities are reputed to be maintained by ongoing activity into the spinal cord, which, in the neuritis model, is mainly generated from intact C-fiber neurons. The hyperpolarization-activated cyclic nucleotide-gated (HCN) family of ion channels has been implicated in nerve injury-induced pain hypersensitivities. The present study has examined the role of these channels in the development of heat and mechanical hypersensitivities in the neuritis model. The systemic administration of the HCN-specific blocker ZD7288 produced a reversal of heat but not mechanical hypersensitivity within one hour post-administration. Recordings from C-fiber neurons were performed to determine whether ZD7288 acts by inhibiting ongoing activity. ZD7288 (0.5 mM) caused a 44.1% decrease in the ongoing activity rate following its application to the neuritis site. Immunohistochemical examination of the HCN2 channel subtype within the L5 dorsal root ganglia revealed an increase in expression in neuronal cell bodies of all sizes post-neuritis. In conclusion, HCN channels contribute to the development of neuritis-induced heat hypersensitivity and ongoing activity. Drugs that target HCN channels may be beneficial in the treatment of neuropathic pain in patients with nerve inflammation.

Item Type: Article
Schools and Departments: Brighton and Sussex Medical School > Clinical and Laboratory Investigation
Subjects: Q Science > QP Physiology > QP0351 Neurophysiology and neuropsychology > QP0361 Nervous system
R Medicine > RC Internal medicine > RC0321 Neurosciences. Biological psychiatry. Neuropsychiatry > RC0346 Neurology. Diseases of the nervous system Including speech disorders
Depositing User: Andrew Dilley
Date Deposited: 17 Sep 2014 14:56
Last Modified: 06 Nov 2014 10:23
URI: http://sro.sussex.ac.uk/id/eprint/49957
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