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 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.
Department of Orthopaedic Surgery, Ehime University School of Medicine, Tohon-City, Ehime 791-0295, Japan.
Masayuki
M
Hino
Tadanori
T
Ogata
Tadao
T
Morino
Hideki
H
Horiuchi
Haruyasu
H
Yamamoto
D000818:Animals; D002478:Cells, Cultured; D004744:Enkephalin, Methionine / Q000378:metabolism; D004745:Enkephalins / Q000378:metabolism*; D006358:Hot Temperature; D006801:Humans; D006930:Hyperalgesia / Q000209:etiology / Q000503:physiopathology / Q000628:therapy*; D007278:Injections, Spinal; D008264:Macrophages / Q000502:physiology* / Q000637:transplantation*; D008297:Male; D010146:Pain / Q000209:etiology / Q000503:physiopathology; D059408:Pain Management; D010147:Pain Measurement; D011498:Protein Precursors / Q000378:metabolism*; D012333:RNA, Messenger / Q000378:metabolism; D051381:Rats; D017208:Rats, Wistar; D020426:Sciatic Neuropathy / Q000150:complications / Q000503:physiopathology / Q000628:therapy*; D013116:Spinal Cord / Q000503:physiopathology; D013997:Time Factors; D014162:Transfection; D014182:Transplantation, Autologous
D004745:Enkephalins; D011498:Protein Precursors; D012333:RNA, Messenger; C029992:proenkephalin; D004744:Enkephalin, Methionine