Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats

C. Y. Lu, A. K. Chou, C. L. Wu, C. H. Yang, J. T. Chen, P. C. Wu, S. H. Lin, R. Muhammad, L. C. Yang

研究成果: Article

33 引文 (Scopus)

摘要

Endogenous opioid peptides play an essential role in the intrinsic modulation and control of inflammatory pain, and could be therapeutically useful. These opioid peptides are synthesized as parts of larger precursor molecules. One such precursor molecule is pro-opiomelanocortin (POMC). In this study, we developed a gene-gun method for the transfer of POMC cDNA in vivo, and investigated its therapeutic effect on inflammatory pain in a rat model of formalin-induced pain. Human POMC cDNA was cloned into a modified pCMV plasmid and delivered to the skin of rats by gene gun. Three days after gene-gun injection, 1 % formalin was injected. Endorphin levels were measured in the serum and skin after the tormalin test, and skin histology was used to detect endorphin after green fluorescent protein (GFP; control) or POMC cDNA transfer. There was no significant difference in the results of acute nociceptive tests between the experimental and control groups. There was also no difference in response between the groups to phase 1 of the formalin test. However, rats which received POMC cDNA via gene-gun injection showed a significantly reduced response in phase 2 of the formalin test. Endorphin immunoreactivity in the skin increased approximately three- to four-fold in experimental animals compared with GFP-treated controls at day 3 after injection. The phase 2 response in animals treated with formalin and naloxone did not differ significantly from the control, implying that the analgesic effects of POMC cDNA particle injection in phase 2 of the formalin test are reversed by naloxone. There are two major findings from this study. First, in vivo DNA delivery by gene gun to the skin is feasible. Second, the production of β-endorphin is insufficient to block phasic pain, but is effective against sensitization of the afferent neurons during phase 2 of the formalin test.

原文English
頁(從 - 到)1008-1014
頁數7
期刊Gene Therapy
9
發行號15
DOIs
出版狀態Published - 2002 八月 27

指紋

Pro-Opiomelanocortin
Firearms
Analgesia
Formaldehyde
Endorphins
Complementary DNA
Pain Measurement
Pain
Genes
Skin
Injections
Opioid Peptides
Naloxone
Afferent Neurons
Therapeutic Uses
Green Fluorescent Proteins
Skin Tests
Analgesics
Histology
Plasmids

All Science Journal Classification (ASJC) codes

  • Molecular Medicine
  • Molecular Biology
  • Genetics

引用此文

Lu, C. Y. ; Chou, A. K. ; Wu, C. L. ; Yang, C. H. ; Chen, J. T. ; Wu, P. C. ; Lin, S. H. ; Muhammad, R. ; Yang, L. C. / Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats. 於: Gene Therapy. 2002 ; 卷 9, 編號 15. 頁 1008-1014.
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title = "Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats",
abstract = "Endogenous opioid peptides play an essential role in the intrinsic modulation and control of inflammatory pain, and could be therapeutically useful. These opioid peptides are synthesized as parts of larger precursor molecules. One such precursor molecule is pro-opiomelanocortin (POMC). In this study, we developed a gene-gun method for the transfer of POMC cDNA in vivo, and investigated its therapeutic effect on inflammatory pain in a rat model of formalin-induced pain. Human POMC cDNA was cloned into a modified pCMV plasmid and delivered to the skin of rats by gene gun. Three days after gene-gun injection, 1 {\%} formalin was injected. Endorphin levels were measured in the serum and skin after the tormalin test, and skin histology was used to detect endorphin after green fluorescent protein (GFP; control) or POMC cDNA transfer. There was no significant difference in the results of acute nociceptive tests between the experimental and control groups. There was also no difference in response between the groups to phase 1 of the formalin test. However, rats which received POMC cDNA via gene-gun injection showed a significantly reduced response in phase 2 of the formalin test. Endorphin immunoreactivity in the skin increased approximately three- to four-fold in experimental animals compared with GFP-treated controls at day 3 after injection. The phase 2 response in animals treated with formalin and naloxone did not differ significantly from the control, implying that the analgesic effects of POMC cDNA particle injection in phase 2 of the formalin test are reversed by naloxone. There are two major findings from this study. First, in vivo DNA delivery by gene gun to the skin is feasible. Second, the production of β-endorphin is insufficient to block phasic pain, but is effective against sensitization of the afferent neurons during phase 2 of the formalin test.",
author = "Lu, {C. Y.} and Chou, {A. K.} and Wu, {C. L.} and Yang, {C. H.} and Chen, {J. T.} and Wu, {P. C.} and Lin, {S. H.} and R. Muhammad and Yang, {L. C.}",
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Lu, CY, Chou, AK, Wu, CL, Yang, CH, Chen, JT, Wu, PC, Lin, SH, Muhammad, R & Yang, LC 2002, 'Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats', Gene Therapy, 卷 9, 編號 15, 頁 1008-1014. https://doi.org/10.1038/sj.gt.3301774

Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats. / Lu, C. Y.; Chou, A. K.; Wu, C. L.; Yang, C. H.; Chen, J. T.; Wu, P. C.; Lin, S. H.; Muhammad, R.; Yang, L. C.

於: Gene Therapy, 卷 9, 編號 15, 27.08.2002, p. 1008-1014.

研究成果: Article

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T1 - Gene-gun particle with pro-opiomelanocortin cDNA produces analgesia against formalin-induced pain in rats

AU - Lu, C. Y.

AU - Chou, A. K.

AU - Wu, C. L.

AU - Yang, C. H.

AU - Chen, J. T.

AU - Wu, P. C.

AU - Lin, S. H.

AU - Muhammad, R.

AU - Yang, L. C.

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N2 - Endogenous opioid peptides play an essential role in the intrinsic modulation and control of inflammatory pain, and could be therapeutically useful. These opioid peptides are synthesized as parts of larger precursor molecules. One such precursor molecule is pro-opiomelanocortin (POMC). In this study, we developed a gene-gun method for the transfer of POMC cDNA in vivo, and investigated its therapeutic effect on inflammatory pain in a rat model of formalin-induced pain. Human POMC cDNA was cloned into a modified pCMV plasmid and delivered to the skin of rats by gene gun. Three days after gene-gun injection, 1 % formalin was injected. Endorphin levels were measured in the serum and skin after the tormalin test, and skin histology was used to detect endorphin after green fluorescent protein (GFP; control) or POMC cDNA transfer. There was no significant difference in the results of acute nociceptive tests between the experimental and control groups. There was also no difference in response between the groups to phase 1 of the formalin test. However, rats which received POMC cDNA via gene-gun injection showed a significantly reduced response in phase 2 of the formalin test. Endorphin immunoreactivity in the skin increased approximately three- to four-fold in experimental animals compared with GFP-treated controls at day 3 after injection. The phase 2 response in animals treated with formalin and naloxone did not differ significantly from the control, implying that the analgesic effects of POMC cDNA particle injection in phase 2 of the formalin test are reversed by naloxone. There are two major findings from this study. First, in vivo DNA delivery by gene gun to the skin is feasible. Second, the production of β-endorphin is insufficient to block phasic pain, but is effective against sensitization of the afferent neurons during phase 2 of the formalin test.

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