Jiangru Hong1, Jie Qiu1, Xiniao Wang1, Guangqin Zhang2. 1. Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. 2. Department of Clinical Pharmacy, China Pharmaceutical University, Nanjing, 210009, China. njzhanggq@163.com.
Abstract
OBJECTIVE: To evaluate the role of K+ channels in pain following gouty arthritis. METHODS: The model of acute gouty arthritis was induced by monosodium urate (MSU) in mice. The swelling degree was determined by measuring the circumference of the ankle joint. Mechanical hyperalgesia was detected by von Frey filaments. Two types of K+ currents, A-type currents (IA) and delayed rectifier currents (IK), were recorded in dorsal root ganglion (DRG) neurons using patch-clamp techniques. RESULTS: The swelling degree reached its maximum at 10 h and the minimum pain threshold was maintained between 8 and 48 h after MSU treatment in mice. The amplitudes of IA and IK in DRG neurons were moderately increased on day 1 after MSU treatment, and then, they were gradually decreased with times and reached their minimums on day 4 (for IA) or 5 (for IK). Compared with control group, the activation curve of IA was significantly shifted to more positive potential and the recovery time of IA from inactivation was markedly prolonged, but inactivation and frequency dependence of IA appeared unaffected in MSU-treated group. Additionally, no change was observed in the activation curve of IK after MSU treatment. The excitability was significantly higher in the MSU group than in the control group. CONCLUSIONS: MSU-induced gout pain may be related to the hyperexcitability of DRG neurons elicited by decreasing K+ currents.
OBJECTIVE: To evaluate the role of K+ channels in pain following gouty arthritis. METHODS: The model of acute gouty arthritis was induced by monosodium urate (MSU) in mice. The swelling degree was determined by measuring the circumference of the ankle joint. Mechanical hyperalgesia was detected by von Frey filaments. Two types of K+ currents, A-type currents (IA) and delayed rectifier currents (IK), were recorded in dorsal root ganglion (DRG) neurons using patch-clamp techniques. RESULTS: The swelling degree reached its maximum at 10 h and the minimum pain threshold was maintained between 8 and 48 h after MSU treatment in mice. The amplitudes of IA and IK in DRG neurons were moderately increased on day 1 after MSU treatment, and then, they were gradually decreased with times and reached their minimums on day 4 (for IA) or 5 (for IK). Compared with control group, the activation curve of IA was significantly shifted to more positive potential and the recovery time of IA from inactivation was markedly prolonged, but inactivation and frequency dependence of IA appeared unaffected in MSU-treated group. Additionally, no change was observed in the activation curve of IK after MSU treatment. The excitability was significantly higher in the MSU group than in the control group. CONCLUSIONS:MSU-induced gout pain may be related to the hyperexcitability of DRG neurons elicited by decreasing K+ currents.