期刊
NEUROPHARMACOLOGY
卷 113, 期 -, 页码 217-230出版社
PERGAMON-ELSEVIER SCIENCE LTD
DOI: 10.1016/j.neuropharm.2016.10.012
关键词
Bee venom; Large-sized DRG neurons; Hyperexcitability; Hyperpolarization-activated cation channel; Cyclooxygenases 1; Prostaglandin E2
资金
- NSFC [31300919, 31400948]
- National Basic Research Program of China [2013CB835100]
- National Key Technology Support Program of China [2013BAI04B04]
- US National Institutes of Health [NS 040723]
Under physiological state, small- and medium-sized dorsal root ganglia (DRG) neurons are believed to mediate nociceptive behavioral responses to painful stimuli. However, recently it has been found that a number of large-sized neurons are also involved in nociceptive transmission under neuropathic conditions. Nonetheless, the underlying mechanisms that large-sized DRG neurons mediate nociception are poorly understood. In the present study, the role of large-sized neurons in bee venom (BV)-induced mechanical allodynia and the underlying mechanisms were investigated. Behaviorally, it was found that mechanical allodynia was still evoked by BV injection in rats in which the transient receptor potential vanilloid 1-positive DRG neurons were chemically deleted. Electrophysiologically, in vitro patch clamp recordings of large-sized neurons showed hyperexcitability in these neurons. Interestingly, the firing pattern of these neurons was changed from phasic to tonic under BV-inflamed state. It has been suggested that hyperpolarization-activated cyclic nucleotide gated channels (HCN) expressed in large-sized DRG neurons contribute importantly to repeatedly firing. So we examined the roles of HCNs in By induced mechanical allodynia. Consistent with the overexpression of HCN1/2 detected by immunofluorescence, HCNs-mediated hyperpolarization activated cation current (I-h) was significantly increased in the BV treated samples. Pharmacological experiments demonstrated that the hyperexcitability and upregulation of I-h in large-sized neurons were mediated by cyclooxygenase-1 (COX-1)-prostaglandin E2 pathway. This is evident by the fact that the COX-1 inhibitor significantly attenuated the BV-induced mechanical allodynia. These results suggest that BV can excite the large-sized DRG neurons at least in part by increasing hi through activation of COX-1. (C) 2016 Elsevier Ltd. All rights reserved.
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