Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

Evidence-Based Complementary and Alternative Medicine, Dec 2017

Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms.

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Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats

Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats Zhiyong Wang 0 1 Jianwei Wang 0 Lihua Qin 0 Weiguang Zhang 0 Ke Ren 0 Department of Anatomy and Histo-Embryology, School of Basic Medical Sciences, Peking University , Beijing 100191 , China 1 Key Lab for Neuroscience, Ministry of Education/National Health and Family Planning Commission of China, Peking University , Beijing 100191 , China Neuropathic pain is common in clinical practice. Exploration of new drug therapeutics has always been carried out for more satisfactory effects and fewer side-effects. In the present study, we aimed to investigate effects of Tongluo Zhitong Prescription (TZP), a compounded Chinese medicine description, on neuropathic pain model of rats with chronic constriction injury (CCI). The CCI model was established by loosely ligating sciatic nerve with catgut suture, proximal to its trifurcation. The static and dynamic allodynia, heat hyperalgesia, mechanical allodynia, cold allodynia, and gait were assessed. Our results showed that TZP alleviated CCI-induced static and dynamic allodynia, suppressed heat hyperalgesia and cold and mechanical allodynia, and improved gait function. These results suggest that TZP could alleviate neuropathic pain. Further experiments are needed to explore its mechanisms. 1. Introduction Neuropathic pain is caused by disease or injury of the nervous system, it affects up to 8% population [ 1 ]. Allodynia and hyperalgesia are prominent symptoms in patients with neuropathic pain, experienced either simultaneously or independently [ 2 ]. Current treatments include nonpharmacological, pharmacological, and interventional therapies for pain relief. Pharmacotherapy for neuropathic pain is the main treatment, and currently recommended first-line treatments include antidepressants and anticonvulsants [ 1 ]. However, there are many unsatisfactory aspects about these drugs, such as the limited pain relief and the occurrence of side-effects [ 3?5 ]. Traditional Chinese medicine is widely used to treat various diseases because of the fewer side-effects and may be effective in targeting different pathological mechanisms involved in peripheral nerve injury, avoiding the shortcomings of single factor adjuvant therapy [ 6 ]. TZP consists of Astragalus, Salvia, Scorpion, and Asarum. Astragalus and Salvia could promote the recovery of nerve structure and motor function [ 7, 8 ]; Scorpion and Asarum help to restore the sensory function [ 9, 10 ]. The prescription containing these four herbs mentioned above is expected to alleviate allodynia, hyperalgesia, and dyskinesia of the CCI model in present experiment. In this study, we evaluated TZP using a neuropathic pain model of rats with CCI [ 11 ]. With several behavioral testing paradigms for allodynia, hyperalgesia, and dyskinesia, we found that TZP could alleviate neuropathic pain in rats. 2. Materials and Methods 2.1. Drugs. The composition of TZP was as follows: Astragalus 100 g, Salvia 50 g, Scorpion 20 g, and Asarum 10 g. All medicines were purchased from Beijing, China. They were prepared according to the previous protocol [ 12 ], firstly being mixed and then boiled with 10 volumes of distilled water for 1 h. The boiling was carried out twice, and the mixed solution was concentrated to 1 g/ml and stored at 4?C until use. 2.2. Animals. Adult male SD rats weighing about 250 grams were raised under pathogen-free laboratory conditions on a 12 h light/dark cycle at about 23?C. Rats were divided into three groups: sham group, control group, and treatment group (6 rats in each group). The animals were allowed free access to food and water. Ef forts were made to minimize possible unnecessary animal sufferings; experimental procedures on animals were performed according to the Guidelines for the Care and Use of Laboratory Animals of Peking University. The study protocol was approved by the Medical Ethics Review Committee of Peking University (Beijing, China). 2.3. CCI Model. CCI model was made according to described methods [ 11 ]. Rats in the control and treatment groups were anesthetized with Ketamine (80 mg/kg) and Xylazine (10 mg/kg). The right sciatic nerve was exposed at the level of the trifurcation. Four ligatures (chromic catgut suture 4/0) were placed loosely around the nerve, 1 mm apart, and proximal to the trifurcation of the sciatic nerve. Ligatures were tied; the constriction to the diameter of the sciatic nerve was barely discernable. When a brief twitch was observed, the constriction was immediately stopped. In the sham group, the nerve was exposed without ligation. Finally, the incisions were sutured. 2.4. Method of Administration. Starting from the first day after surgery, rats in the treatment group were treated with 2 ml TZP solution (1 g/ml) by oral gavage once daily, while rats in the sham and control groups were treated with 2 ml 0.9% NaCl in the same (...truncated)


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Zhiyong Wang, Jianwei Wang, Lihua Qin, Weiguang Zhang. Tongluo Zhitong Prescription Alleviates Allodynia, Hyperalgesia, and Dyskinesia in the Chronic Constriction Injury Model of Rats, Evidence-Based Complementary and Alternative Medicine, 2017, 2017, DOI: 10.1155/2017/8197281