ABSTRACT
Peripheral nerves are most commonly affected by pressure, traction, friction, anoxia or cutting and these injuries can easily cause allodynia of the limbs. Beta-endorphin is an endogenous pain inhibitor. It can produce profound and long-lasting analgesia for patients with intractable pain. Prominent endogenous opioid peptides are modulated by the hypothalamic-pituitary-adrenal axis. The expression of pro-opiomelanocortin (POMC) produces opioid peptides, including the beta-endorphins, other shorter endorphins, adrenocorticotropic hormones (ACTH), and melanocyte-stimulating hormones (MSH). The aim of this study is to evaluate the efficacy of POMC gene therapy for neuropathic pain that is caused by chronic constriction injury (CCI) in a rat model. Experimental painful peripheral neuropathy is induced by CCI of the sciatic nerve which results in allodynia of the hind limb. We used the method of conventional electrical stimulation to quantitatively analyze the efficacy of gene therapy. In addition, two nociceptive tests, including thermal-withdrawal latency and mechanical withdrawal threshold, were also conducted to evaluate the effect of treatment. Adult male Sprague Dawley rats (250-300 g, n = 24) were divided into three groups: (1) the control group (n = 8); (2) the sciatic nerve ligation group that received an injection of adenoviral vectors with green fluorescent protein (Ad-GFP) (n = 8); and (3) the sciatic nerve ligation group that received an injection of adenoviral vectors with POMC gene (Ad-POMC) (n = 8). The electrophysiological studies and nociceptive tests were carried out on day 3 before ligation and days 3, 7 and 14 after ligation. The POMC injection was performed on day 3 after ligation. We measured the amplitude and onset latency of maximal compound muscle action potential (CMAP) in braches of the sciatic nerve (nerves to the gastrocnemius, tibialis anterior), motor nerve conduction velocity, H-reflex and F-wave by electrical stimulation and denervation sign by electromyography (gastrocnemius, tibialis anterior). In addition, the latency of the thermal-withdrawal and threshold of mechanical withdrawal were also recorded. The results showed that prominent thermal-withdrawal latencies and mechanical withdrawal thresholds were elevated in the sciatic nerve ligation group with POMC gene therapy on days 14 and 21 after ligation. It also demonstrated that administrations of POMC gene therapy which produced the beta-endorphins to elevate the pain threshold and reduced the allodynia of the injured limbs. In conventional electrophysiological studies, no significant differences were noted between the Ad-GFP and Ad-POMC groups. The reduction of CMAP amplitude was recorded in rats of the sciatic nerve ligation groups. There was no significant difference in the mean onset latency of CMAP and nerve conduction velocity (NCV) within these three groups, except for the fact that the NCV of the tibial nerve was slowing in the Ad-GFP group on day 14. Electrophysiological analysis was revealed prolonged or absent H-reflex and F-wave in animals of the neuropathy groups by electrical stimulation. Electromyography showed prominent denervation potentials over the sampling muscles in the sciatic nerve ligation groups. In conclusion, POMC gene therapy for neuropathic pain is very efficacious. However, the influence of POMC gene therapy for nerve protection or minimizing the progress of nerve injury will require further investigations.
| Identifer | oai:union.ndltd.org:NSYSU/oai:NSYSU:etd-0127107-204124 |
| Date | 27 January 2007 |
| Creators | Wang, I-Chou |
| Contributors | Ming-Hong Tai, Hung-Tu Huang, Zhi-Hong Wen |
| Publisher | NSYSU |
| Source Sets | NSYSU Electronic Thesis and Dissertation Archive |
| Language | English |
| Detected Language | English |
| Type | text |
| Format | application/pdf |
| Source | http://etd.lib.nsysu.edu.tw/ETD-db/ETD-search/view_etd?URN=etd-0127107-204124 |
| Rights | withheld, Copyright information available at source archive |
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