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Peripheral hyperpolarization‐activated cyclic nucleotide‐gated channels contribute to inflammation‐induced hypersensitivity of the rat temporomandibular joint
Author(s) -
Hatch R.J.,
Jennings E.A.,
Ivanusic J.J.
Publication year - 2013
Publication title -
european journal of pain
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 1.305
H-Index - 109
eISSN - 1532-2149
pISSN - 1090-3801
DOI - 10.1002/j.1532-2149.2012.00261.x
Subject(s) - hcn channel , temporomandibular joint , trigeminal ganglion , hyperpolarization (physics) , chemistry , peripheral , inflammation , nociception , channel blocker , medicine , pharmacology , sensory system , neuroscience , ion channel , pathology , receptor , biology , stereochemistry , calcium , nuclear magnetic resonance spectroscopy
Background Hyperpolarization‐activated cyclic nucleotide‐gated ( HCN ) channels conduct an inward cation current ( I h ) 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 F reund's adjuvant; CFA )‐induced mechanical hypersensitivity of the rat TMJ was tested with injections of the HCN channel blocker ZD 7288. 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 ZD 7288 with the CFA ( n = 7). Retrograde labelling and immunohistochemistry experiments revealed expression predominantly of HCN 1 and HCN 2 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.