Orofacial pain disorders encompass a wide range of conditions including trigeminal neuralgia, reflex sympathetic dystrophy (RSD) of the face, temporomandibular joint disorders, periodontal pain, burning mouth syndrome, dental surgical pain, head and neck cancer pain, pain due to oral infections, and other neuropathic and inflammatory pain conditions. One common symptom in many chronic orofacial pain conditions is the severe painful sensation induced by cooling temperatures that would normally produce innocuous or pleasant cooling sensation. Unfortunately, the current clinical treatments are unsatisfactory for this chronic orofacial pain condition. This is largely due to the poor understanding of sensory coding mechanisms for cold stimuli in trigeminal sensory system. Several ion channels including TRPM8, TRPA1 and K2P have recently be proposed to be candidates of cold-sensing receptors. The overall goal of this proposal is to identify, in chronic orofacial pain conditions, I) Which of these cold-sensing receptor candidates are involved in innocuous cold- induced orofacial pain, and II) What peripheral and central neuronal mechanisms are responsible for the maintenance of chronic orofacial pain induced by innocuous cold. Advanced neurological techniques including patch-clamp records and calcium imaging together with other approaches including retrograde tracing, immunostaining and animal models will be used in this project. By accomplishing our goal, we will have identified novel therapeutic targets for treating some intractable orofacial pain conditions.
Orofacial pain conditions are significant clinical problems that have not been treated satisfactorily due to the poor understanding of neuronal and molecular mechanisms. This project will use advanced neurobiological approaches and animal models to identify thermal receptors and neuronal mechanisms that are involved in an orofacial pain state induced by innocuous (non-painful) cold temperatures, a condition seen in patients with trigeminal neuropathy and other pathological disorders in orofacial regions. The accomplishment of the Aims proposed in this project will lead to novel therapeutic targets for treating some orofacial pain conditions. ? ? ?
|Viatchenko-Karpinski, Viacheslav; Ling, Jennifer; Gu, Jianguo G (2018) Characterization of temperature-sensitive leak K+ currents and expression of TRAAK, TREK-1, and TREK2 channels in dorsal root ganglion neurons of rats. Mol Brain 11:40|
|Ling, Jennifer; Erol, Ferhat; Gu, Jianguo G (2018) Role of KCNQ2 channels in orofacial cold sensitivity: KCNQ2 upregulation in trigeminal ganglion neurons after infraorbital nerve chronic constrictive injury. Neurosci Lett 664:84-90|
|Viatchenko-Karpinski, Viacheslav; Ling, Jennifer; Gu, Jianguo G (2018) Down-regulation of Kv4.3 channels and a-type K+ currents in V2 trigeminal ganglion neurons of rats following oxaliplatin treatment. Mol Pain 14:1744806917750995|
|Kanda, Hirosato; Gu, Jianguo G (2017) Membrane Mechanics of Primary Afferent Neurons in the Dorsal Root Ganglia of Rats. Biophys J 112:1654-1662|
|Kanda, Hirosato; Gu, Jianguo G (2017) Effects of cold temperatures on the excitability of rat trigeminal ganglion neurons that are not for cold sensing. J Neurochem 141:532-543|
|Chang, Weipang; Kanda, Hirosato; Ikeda, Ryo et al. (2017) Serotonergic transmission at Merkel discs: modulation by exogenously applied chemical messengers and involvement of Ih currents. J Neurochem 141:565-576|
|Ling, Jennifer; Erol, Ferhat; Viatchenko-Karpinski, Viacheslav et al. (2017) Orofacial neuropathic pain induced by oxaliplatin: downregulation of KCNQ2 channels in V2 trigeminal ganglion neurons and treatment by the KCNQ2 channel potentiator retigabine. Mol Pain 13:1744806917724715|
|Chang, Weipang; Kanda, Hirosato; Ikeda, Ryo et al. (2016) Merkel disc is a serotonergic synapse in the epidermis for transmitting tactile signals in mammals. Proc Natl Acad Sci U S A 113:E5491-500|
|Ikeda, Ryo; Gu, Jianguo (2016) Electrophysiological property and chemical sensitivity of primary afferent neurons that innervate rat whisker hair follicles. Mol Pain 12:|
|Kanda, Hirosato; Clodfelder-Miller, Buffie J; Gu, Jianguo G et al. (2016) Electrophysiological properties of lumbosacral primary afferent neurons innervating urothelial and non-urothelial layers of mouse urinary bladder. Brain Res 1648:81-89|
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