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Browsing by Author "Ji, Yong-Hua"
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Item Brain natriuretic peptide suppresses pain induced by BmK I, a sodium channel-specific modulator, in rats.(Springer, 2016) Li, Zheng-Wei; Wu, Bin; Ye, Pin; Tan, Zhi-Yong; Ji, Yong-Hua; Department of Pharmacology and Toxicology, IU School of MedicineBackground: A previous study found that brain natriuretic peptide (BNP) inhibited inflammatory pain via activating its receptor natriuretic peptide receptor A (NPRA) in nociceptive sensory neurons. A recent study found that functional NPRA is expressed in almost all the trigeminal ganglion (TG) neurons at membrane level suggesting a potentially important role for BNP in migraine pathophysiology. Methods: An inflammatory pain model was produced by subcutaneous injection of BmK I, a sodium channel-specific modulator from venom of Chinese scorpion Buthus martensi Karsch. Quantitative PCR, Western Blot, and immunohistochemistry were used to detect mRNA and protein expression of BNP and NPRA in dorsal root ganglion (DRG) and dorsal horn of spinal cord. Whole-cell patch clamping experiments were conducted to record large-conductance Ca2+-activated K+ (BKCa) currents of membrane excitability of DRG neurons. Spontaneous and evoked pain behaviors were examined. Results: The mRNA and protein expression of BNP and NPRA was up-regulated in DRG and dorsal horn of spinal cord after BmK I injection. The BNP and NPRA was preferentially expressed in small-sized DRG neurons among which BNP was expressed in both CGRP-positive and IB4-positive neurons while NPRA was preferentially expressed in CGRP-positive neurons. BNP increased the open probability of BKCa channels and suppressed the membrane excitability of small-sized DRG neurons. Intrathecal injection of BNP significantly inhibited BmK-induced pain behaviors including both spontaneous and evoked pain behaviors. Conclusions: These results suggested that BNP might play an important role as an endogenous pain reliever in BmK I-induced inflammatory pain condition. It is also suggested that BNP might play a similar role in other pathophysiological pain conditions including migraine.Item Differential expression of slow and fast-repriming tetrodotoxin-sensitive sodium currents in dorsal root ganglion neurons(Frontiers Media, 2024-01-11) Tan, Zhi-Yong; Wu, Bin; Su, Xiaolin; Zhou, You; Ji, Yong-Hua; Biochemistry and Molecular Biology, School of MedicineSodium channel Nav1.7 triggers the generation of nociceptive action potentials and is important in sending pain signals under physiological and pathological conditions. However, studying endogenous Nav1.7 currents has been confounded by co-expression of multiple sodium channel isoforms in dorsal root ganglion (DRG) neurons. In the current study, slow-repriming (SR) and fast-repriming (FR) tetrodotoxin-sensitive (TTX-S) currents were dissected electrophysiologically in small DRG neurons of both rats and mice. Three subgroups of small DRG neurons were identified based on the expression pattern of SR and FR TTX-S currents. A majority of rat neurons only expressed SR TTX-S currents, while a majority of mouse neurons expressed additional FR TTX-S currents. ProTx-II inhibited SR TTX-S currents with variable efficacy among DRG neurons. The expression of both types of TTX-S currents was higher in Isolectin B4-negative (IB4−) compared to Isolectin B4-positive (IB4+) neurons. Paclitaxel selectively increased SR TTX-S currents in IB4− neurons. In simulation experiments, the Nav1.7-expressing small DRG neuron displayed lower rheobase and higher frequency of action potentials upon threshold current injections compared to Nav1.6. The results suggested a successful dissection of endogenous Nav1.7 currents through electrophysiological manipulation that may provide a useful way to study the functional expression and pharmacology of endogenous Nav1.7 channels in DRG neurons.Item Inhibitory Effects of Columbianadin on Nociceptive Behaviors in a Neuropathic Pain Model, and on Voltage-Gated Calcium Currents in Dorsal Root Ganglion Neurons in Mice(Frontiers Media, 2020-01-09) Su, Xiaolin; Wu, Bin; Zhang, Wentong; Ji, Yong-Hua; Wang, Qiuhong; Tan, Zhi-Yong; Pharmacology and Toxicology, School of MedicineRadix angelicae pubescentis (RAP) has been used in Chinese traditional medicine to treat painful diseases such as rheumatism and headache. A previous study has reported that columbianadin (CBN), a major coumarin in RAP inhibits acute and inflammatory pain behaviors. However, the effects of CBN on neuropathic pain behaviors, and the potential underlying mechanism have not been reported. In the present study, the effects of CBN, compared to another major coumarin of RAP osthole (OST), on oxaliplatin-induced neuropathic pain behaviors and on the voltage-gated calcium currents in small dorsal root ganglion (DRG) neurons were studied in mice. It was found that CBN and OST inhibited both mechanical and cold hypersensitivity induced by oxaliplatin. Moreover, CBN and OST might preferentially inhibit T- and L-type calcium currents (Ica). The inhibitory effects of CBN and OST on the oxaliplatin-induced mechanical allodynia were prevented by gabapentin. These results suggest that CBN, as well as OST might inhibit neuropathic pain behaviors through an inhibition of T- and L-type calcium currents in nociceptive DRG neurons.Item Oxaliplatin Depolarizes the IB4– Dorsal Root Ganglion Neurons to Drive the Development of Neuropathic Pain Through TRPM8 in Mice(Frontiers Media, 2021-06-04) Wu, Bin; Su, Xiaolin; Zhang, Wentong; Zhang, Yi-Hong; Feng, Xinghua; Ji, Yong-Hua; Tan, Zhi-Yong; Pharmacology and Toxicology, School of MedicineUse of chemotherapy drug oxaliplatin is associated with painful peripheral neuropathy that is exacerbated by cold. Remodeling of ion channels including TRP channels in dorsal root ganglion (DRG) neurons contribute to the sensory hypersensitivity following oxaliplatin treatment in animal models. However, it has not been studied if TRP channels and membrane depolarization of DRG neurons serve as the initial ionic/membrane drives (such as within an hour) that contribute to the development of oxaliplatin-induced neuropathic pain. In the current study, we studied in mice (1) in vitro acute effects of oxaliplatin on the membrane excitability of IB4+ and IB4– subpopulations of DRG neurons using a perforated patch clamping, (2) the preventative effects of a membrane-hyperpolarizing drug retigabine on oxaliplatin-induced sensory hypersensitivity, and (3) the preventative effects of TRP channel antagonists on the oxaliplatin-induced membrane hyperexcitability and sensory hypersensitivity. We found (1) IB4+ and IB4– subpopulations of small DRG neurons displayed previously undiscovered, substantially different membrane excitability, (2) oxaliplatin selectively depolarized IB4– DRG neurons, (3) pretreatment of retigabine largely prevented oxaliplatin-induced sensory hypersensitivity, (4) antagonists of TRPA1 and TRPM8 channels prevented oxaliplatin-induced membrane depolarization, and (5) the antagonist of TRPM8 largely prevented oxaliplatin-induced sensory hypersensitivity. These results suggest that oxaliplatin depolarizes IB4– neurons through TRPM8 channels to drive the development of neuropathic pain and targeting the initial drives of TRPM8 and/or membrane depolarization may prevent oxaliplatin-induce neuropathic pain.Item Up-Regulation of Akt and Nav1.8 in BmK I-Induced Pain(Springer Nature, 2018-06) Zhou, Guokun; Jiao, Yunlu; Zhou, You; Qin, Shichao; Tao, Jie; Jiang, Feng; Tan, Zhi-Yong; Ji, Yong-Hua; Pharmacology and Toxicology, School of Medicine