Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats

To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperi...

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Veröffentlicht in:Neuroscience research 2009-05, Vol.64 (1), p.56-62
Hauptverfasser: Hino, Masayuki, Ogata, Tadanori, Morino, Tadao, Horiuchi, Hideki, Yamamoto, Haruyasu
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creator Hino, Masayuki
Ogata, Tadanori
Morino, Tadao
Horiuchi, Hideki
Yamamoto, Haruyasu
description To develop a novel genetic approach for the treatment of pain, we tested the transplantation of gene-transferred autologous macrophages by lumbar puncture. A rat neuropathic pain model was produced by chronic constriction of the sciatic nerve. Autologous macrophages were collected from the intraperitoneal space. Then human proenkephalin gene was transferred into the macrophages by electroporation. The gene-transferred macrophages were transplanted into the subarachnoid space by lumbar puncture. One week after transplantation, the heat hyperalgesia and allodynia induced by sciatic nerve constriction completely remitted. The analgesic action continued until at least 4 weeks after transplantation. The transplanted macrophages migrated into the spinal cord and expressed proenkephalin mRNA and Met-enkephalin protein. The method we tested in the present study may be a safe, simple and effective way to inhibit pain sensation after peripheral nerve injuries.
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subjects Allodynia
Animals
Cells, Cultured
Enkephalin, Methionine - metabolism
Enkephalins - metabolism
Gene transfer
Hot Temperature
Humans
Hyperalgesia
Hyperalgesia - etiology
Hyperalgesia - physiopathology
Hyperalgesia - therapy
Injections, Spinal
Macrophage
Macrophages - physiology
Macrophages - transplantation
Male
Neuropathic pain
Pain - etiology
Pain - physiopathology
Pain Management
Pain Measurement
Proenkephalin
Protein Precursors - metabolism
Rats
Rats, Wistar
RNA, Messenger - metabolism
Sciatic Neuropathy - complications
Sciatic Neuropathy - physiopathology
Sciatic Neuropathy - therapy
Spinal Cord - physiopathology
Time Factors
Transfection
Transplantation, Autologous
title Intrathecal transplantation of autologous macrophages genetically modified to secrete proenkephalin ameliorated hyperalgesia and allodynia following peripheral nerve injury in rats
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