Evaluation of the Therapeutic Efficacy of Entrapment Neuropathy Unties (ENUs) Pharmacoacupuncture in Neuropathic Pain Caused by Sciatic Nerve Ligation (SNL) in Mice

Evaluation of the Therapeutic Efficacy of Entrapment Neuropathy Unties (ENUs) Pharmacoacupuncture in Neuropathic Pain Caused by Sciatic Nerve Ligation (SNL) in Mice

Background:

Peripheral nerve injuries are commonly encountered clinical problems that often result in severe functional deficits, and in spite of the expanding knowledge on mechanisms of nerve regeneration, outcomes following repair are disappointing [1]. Some of the recent treatment methods for peripheral nerve injuries include nerve repair, nerve grafting, nerve conduits, pharmacological approaches, stem cells, and gene therapy [2]. In East Asian countries, besides typical alternative medical treatment, such as acupuncture and herbal medicine, a new form of acupuncture combining acupuncture with herbal medicine, called pharmacoacupuncture[3], is being utilized in patients with neuropathic pain. This study aimed to evaluate the effects of pharmacopuncture with Entrapment Neuropathy Unties (ENUs) on neuropathic pain after sciatic nerve ligation (SNL) in mice.

Purpose/Objectives:

The first purpose of this study is to inform the participants about recent treatment methods available for peripheral nerve injuries. The second purpose is to provide information about pharmacoacupuncture and its therapeutic approach. Lastly, the study aims to educate the participants about the effects of ENUs pharmacoacupuncture on neuropathic pain induced by sciatic nerve ligation in mice.

Method:

A total of 54 mice were divided into different groups as follows:

1. Normal, n=6

Control and treatment groups were given saline or ENU after SNL modeling.

Control groups received saline as follows:

2. i.m., n=6: injection at the injury site

3. oral, n=6

Treatment groups received ENU injection at the injury site or orally as follows:

(4-8=injection, 9=orally)

4. ENU V1, n=6: ENU V1

5. ENU V2-low, n=6: ENU V2-low concentration

6. ENU V2-middle, n=6: ENU V2-middle concentration

7. ENU V2-high, n=6: ENU V2-high concentration

8. ENU V3, n=6: ENU V3

9. ENU V2-oral, n=6: ENU V2-middle concentration

The effect of mechanical allodynia was assessed using Von Frey filaments, and the expression of c-fos and GFAP was confirmed through immunofluorescent staining in the L4-5 spinal cord region. The mRNA expression of inflammatory markers GFAP, Iba1, Tnf-α, and IL-1β was confirmed using qPCR.

Results:

The administration of ENUs at the injury site reduced mechanical allodynia induced by SNL. Furthermore, it regulated the expression of the neural activity marker C-FOS in the ipsilateral spinal dorsal horn, near the injury site. The increased inflammatory cells and inflammatory cytokines in the spinal dorsal horn due to SNL were decreased by the perilesional administration of ENUs. Oral administration of ENUs also significantly reduced mechanical allodynia and the expression of C-FOS and GFAP in the histological study, as well as the mRNA levels of Iba1, Tnf-a, and IL-1β, compared to the control group.

Conclusions: These results suggest that ENUs pharmacopuncture and oral administration of ENUs may play a significant role in reducing pain and inflammation after ligation injury of the sciatic nerve in mice. ENUs can provide assistance in the treatment of neuropathic pain and can be utilized in the development of novel pain therapies

References: [1]Guntinas-Lichius O, Hundeshagen G, Paling T, Angelov DN. Impact of different types of facial nerve reconstruction on the recovery of motor function: an experimental study in adult rats. Neurosurgery. 2007, 12;61(6):1276-83; discussion 1283-5. doi: 10.1227/01.neu.0000306107.70421.a4. PMID: 18162908.
[2]Yung-Seol Byun, Ha-Jin You, Sang-Uk Lee. The present of peripheral nerve regeneration. J Korean Orthop Assoc 2023; 58: 9-17
[3]J. Park, H. Lee, B.-C. Shin, M. S. Lee, B. Kim, and J.-I. Kim. Pharmacopuncture in Korea: a systematic review and meta-analysis of randomized controlled trials. Evidence-Based Complementary and Alternative Medicine. 2016, Article ID 4683121, pp. 1–19, 2016.