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Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint.
Eur J Pain. 2013 Aug; 17(7):972-82.EJ

Abstract

BACKGROUND

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ).

METHODS

The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ.

RESULTS

Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p < 0.05). The mechanical hypersensitivity generated by CFA injection was blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested.

CONCLUSIONS

Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system.

Authors+Show Affiliations

Department of Anatomy and Neuroscience, Faculty of Medicine, Dentistry and Health Sciences, University of Melbourne, Australia.No affiliation info availableNo affiliation info available

Pub Type(s)

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

Language

eng

PubMed ID

23255289

Citation

Hatch, R J., et al. "Peripheral Hyperpolarization-activated Cyclic Nucleotide-gated Channels Contribute to Inflammation-induced Hypersensitivity of the Rat Temporomandibular Joint." European Journal of Pain (London, England), vol. 17, no. 7, 2013, pp. 972-82.
Hatch RJ, Jennings EA, Ivanusic JJ. Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint. Eur J Pain. 2013;17(7):972-82.
Hatch, R. J., Jennings, E. A., & Ivanusic, J. J. (2013). Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint. European Journal of Pain (London, England), 17(7), 972-82. https://doi.org/10.1002/j.1532-2149.2012.00261.x
Hatch RJ, Jennings EA, Ivanusic JJ. Peripheral Hyperpolarization-activated Cyclic Nucleotide-gated Channels Contribute to Inflammation-induced Hypersensitivity of the Rat Temporomandibular Joint. Eur J Pain. 2013;17(7):972-82. PubMed PMID: 23255289.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Peripheral hyperpolarization-activated cyclic nucleotide-gated channels contribute to inflammation-induced hypersensitivity of the rat temporomandibular joint. AU - Hatch,R J, AU - Jennings,E A, AU - Ivanusic,J J, Y1 - 2012/12/17/ PY - 2012/11/12/accepted PY - 2012/12/21/entrez PY - 2012/12/21/pubmed PY - 2014/3/22/medline SP - 972 EP - 82 JF - European journal of pain (London, England) JO - Eur J Pain VL - 17 IS - 7 N2 - BACKGROUND: Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels conduct an inward cation current (Ih) that contributes to the maintenance of neuronal membrane potential and have been implicated in a number of animal models of neuropathic and inflammatory pain. In the current study, we investigated HCN channel involvement in inflammatory pain of the temporomandibular joint (TMJ). METHODS: The contribution of HCN channels to inflammation (complete Freund's adjuvant; CFA)-induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD7288. Retrograde labelling and immunohistochemistry was used to explore HCN channel expression in sensory neurons that innervate the TMJ. RESULTS: Injection of CFA into the TMJ (n = 7) resulted in a significantly increased mechanical sensitivity relative to vehicle injection (n = 7) (p < 0.05). The mechanical hypersensitivity generated by CFA injection was blocked by co-injection of ZD7288 with the CFA (n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN1 and HCN2 channel subunits in trigeminal ganglion neurons that innervate the TMJ (n = 3). No change in the proportion or intensity of HCN channel expression was found in inflamed (n = 6) versus control (n = 5) animals at the time point tested. CONCLUSIONS: Our findings suggest a role for peripheral HCN channels in inflammation-induced pain of the TMJ. Peripheral application of a HCN channel blocker could provide therapeutic benefit for inflammatory TMJ pain and avoid side effects associated with activation of HCN channels in the central nervous system. SN - 1532-2149 UR - https://www.unboundmedicine.com/medline/citation/23255289/Peripheral_hyperpolarization_activated_cyclic_nucleotide_gated_channels_contribute_to_inflammation_induced_hypersensitivity_of_the_rat_temporomandibular_joint_ L2 - https://doi.org/10.1002/j.1532-2149.2012.00261.x DB - PRIME DP - Unbound Medicine ER -