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| 22KS-018 |
Analgesic effect of Panaphix on neuropathic and diabetic neuropathic pain model of rats
Department
of Anesthesiology and Pain Medicine, Asan Medical Center, University of Ulsan
College of Medicine, Seoul, Republic of Korea
Background
Panaphix (PAX-1, sodium meta-arsenite or NaAsO2) was initially developed as a treatment for various cancer. Human data collected in cancer clinical trials suggest that PAX-1 has the potential analgesic effect. In animal studies, anti-inflammatory and analgesic effect of PAX-1 have been reported. The present study aimed to investigate the analgesic effects of PAX-1 on neuropathic and diabetic neuropathic pain using rat models.
Methods
The analgesic effect of PAX-1 was measured by mechanical allodynia behavior study using von Frey filaments. L5 and L6 spinal nerves of rats were ligated under the dorsal root ganglion to create a neuropathic model. One week after ligation, rats that expressed mechanical allodynia under the von Frey filament test were selected. A total of twenty-four rats were randomly allocated into four groups, respectively; vehicle, 0.1, 1.0, and 10 mg/kg of PAX-1. In diabetic neuropathic model, diabetes was induced by an intraperitoneal injection of 50 mg/kg of streptozotocin. Four weeks later, A total of thirty rats selected in the same method as above were randomly allocated into five groups, respectively; vehicle, 0.1, 1.0, and 10 mg/kg of PAX-1, and sham. After the allocation in both rat models, PAX-1 was orally administered for two weeks, and the von Frey filament test was conducted. The analgesic effect was evaluated by measuring the withdrawal threshold to von Frey filaments.
Results
In neuropathic model, the Von Frey values were significantly increased in PAX-1 groups compared with vehicle. (Postoperative day [POD] 10: vehicle vs. 1.0 and 10 mg/kg of PAX-1, P<0.001; POD 12: vehicle vs 0.1 mg/kg of PAX-1, P=0.02, 1.0 and 10 mg/kg of PAX-1, P<0.001; POD 14: vehicle vs 0.1, 1.0 and 10 mg/kg of PAX-1, P<0.001 in all). In diabetic neuropathic model, the Von Frey values were significantly increased in PAX-1 groups compared with vehicle. (Days after medications [MED] 4: vehicle vs. 10 mg/kg of PAX-1, P<0.001; MED 7: vehicle vs 0.1 mg/kg of PAX-1, P=0.02, 1.0 mg/kg of PAX-1, P=0.01, 10 mg/kg of PAX-1, P<0.001; MED 11: vehicle vs 0.1 and 10 mg/kg of PAX-1, P<0.001, 1.0 mg/kg of PAX-1, P=0.01; MED 14: vehicle vs 0.1 and 10 mg/kg of PAX-1, P<0.001, 1.0 mg/kg of PAX-1, P=0.02).
Conclusion
PAX-1 showed decreased mechanical allodynic behavior in neuropathic and diabetic neuropathic pain models of rats, suggesting PAX-1 may have analgesic effects for these neuropathic pain.
Panaphix (PAX-1, sodium meta-arsenite or NaAsO2) was initially developed as a treatment for various cancer. Human data collected in cancer clinical trials suggest that PAX-1 has the potential analgesic effect. In animal studies, anti-inflammatory and analgesic effect of PAX-1 have been reported. The present study aimed to investigate the analgesic effects of PAX-1 on neuropathic and diabetic neuropathic pain using rat models.
Methods
The analgesic effect of PAX-1 was measured by mechanical allodynia behavior study using von Frey filaments. L5 and L6 spinal nerves of rats were ligated under the dorsal root ganglion to create a neuropathic model. One week after ligation, rats that expressed mechanical allodynia under the von Frey filament test were selected. A total of twenty-four rats were randomly allocated into four groups, respectively; vehicle, 0.1, 1.0, and 10 mg/kg of PAX-1. In diabetic neuropathic model, diabetes was induced by an intraperitoneal injection of 50 mg/kg of streptozotocin. Four weeks later, A total of thirty rats selected in the same method as above were randomly allocated into five groups, respectively; vehicle, 0.1, 1.0, and 10 mg/kg of PAX-1, and sham. After the allocation in both rat models, PAX-1 was orally administered for two weeks, and the von Frey filament test was conducted. The analgesic effect was evaluated by measuring the withdrawal threshold to von Frey filaments.
Results
In neuropathic model, the Von Frey values were significantly increased in PAX-1 groups compared with vehicle. (Postoperative day [POD] 10: vehicle vs. 1.0 and 10 mg/kg of PAX-1, P<0.001; POD 12: vehicle vs 0.1 mg/kg of PAX-1, P=0.02, 1.0 and 10 mg/kg of PAX-1, P<0.001; POD 14: vehicle vs 0.1, 1.0 and 10 mg/kg of PAX-1, P<0.001 in all). In diabetic neuropathic model, the Von Frey values were significantly increased in PAX-1 groups compared with vehicle. (Days after medications [MED] 4: vehicle vs. 10 mg/kg of PAX-1, P<0.001; MED 7: vehicle vs 0.1 mg/kg of PAX-1, P=0.02, 1.0 mg/kg of PAX-1, P=0.01, 10 mg/kg of PAX-1, P<0.001; MED 11: vehicle vs 0.1 and 10 mg/kg of PAX-1, P<0.001, 1.0 mg/kg of PAX-1, P=0.01; MED 14: vehicle vs 0.1 and 10 mg/kg of PAX-1, P<0.001, 1.0 mg/kg of PAX-1, P=0.02).
Conclusion
PAX-1 showed decreased mechanical allodynic behavior in neuropathic and diabetic neuropathic pain models of rats, suggesting PAX-1 may have analgesic effects for these neuropathic pain.