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)