Interleukin-2 gene therapy of chronic neuropathic pain
| Autor: | Ming-Zhong Yao, M.-F. Lang, Zongshan Zhao, Jinjun Liu, Jingjin Gu, Jun Wang, Xiao Liu, Lanying Sun |
|---|---|
| Rok vydání: | 2002 |
| Předmět: |
Male
DNA Complementary Narcotic Antagonists Analgesic Pain (+)-Naloxone Pharmacology Transfection Rats Sprague-Dawley Dorsal root ganglion Threshold of pain medicine Animals Humans Pain Management Tissue Distribution Cation Exchange Resins RNA Messenger Ligation Injections Spinal Pain Measurement Dose-Response Relationship Drug business.industry Naloxone General Neuroscience Genetic Therapy Lipids Recombinant Proteins Rats Disease Models Animal Nociception medicine.anatomical_structure Opioid Organ Specificity Anesthesia Neuropathic pain COS Cells Chronic Disease Liposomes Interleukin-2 Sciatic nerve Sciatic Neuropathy business medicine.drug Signal Transduction |
| Zdroj: | Neuroscience. 112(2) |
| ISSN: | 0306-4522 |
| Popis: | Previous research has revealed an antinociceptive (analgesic) effect of interleukin-2 (IL-2) in central and peripheral nervous systems. Unfortunately IL-2 is very short-lived in vivo, so it is impractical to apply IL-2 for analgesia in clinic. This study was performed to evaluate the effect of intrathecal delivery of human IL-2 gene on rat chronic neuropathic pain induced by chronic constriction injury of the sciatic nerve. Human IL-2 cDNA was cloned into pcDNA3 containing a cytomegalovirus promoter. The paw-withdrawal latency induced by radiant heat was used to measure the pain threshold. The results showed that recombinant human IL-2 had a dose-dependent antinociceptive effect, but that this only lasted for 10-25 min. The pcDNA3-IL-2 or pcDNA3-IL-2/lipofectamine complex in contrast also showed dose-dependent antinociceptive effects, but these reached a peak at day 2-3 and were maintained for up to 6 days. Liposome-mediated pcDNA3-IL-2 produced a more powerful antinociceptive effect than pcDNA3-IL-2 alone. The paw-withdrawal latencies were not affected by control treatments such as vehicle, lipofectamine, pcDNA3, or pcDNA3-lipofectamine. In the experimental groups, human IL-2 mRNA was detected by reverse transcription-polymerase chain reaction in the lumbar spinal pia mater, dorsal root ganglion, sciatic nerve, and spinal dorsal horn, but not in gastrocnemius muscle. The expressed IL-2 profile detected by western blot coincided with its mRNA profile except it was present in the spinal dorsal horn at a higher level. Furthermore, human IL-2 assayed by enzyme-linked immunosorbent assay in cerebrospinal fluid could still be detected at day 6, but lower than day 3. The antinociceptive effect of pcDNA3-IL-2 could be blocked by naloxone, showing some relationship of the antinociceptive effect produced by IL-2 gene to the opioid receptors. It is hoped that the new delivery approach of a single intrathecal injection of the IL-2 gene described here may be of some practical use as a part of a gene therapy for treating neuropathic pain. |
| Databáze: | OpenAIRE |
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