Recombinant herpes vector-mediated analgesia in a primate model of hyperalgesia.
Some chronic pain syndromes are characterized by episodes of intense burning and hyperalgesia in localized areas of skin. These sensations are thought to be mediated, at least in part, by the activity of damaged, unmyelinated C nociceptors. These phenomena were modeled by assaying responses of macaques to thermal and chemical stimuli that produced periodic activation and sensitization of C nociceptors. Upon validation of this method, a recombinant herpes simplex vector encoding human preproenkephalin was topically applied to the dorsal surface of the feet of the monkeys. Immunohistochemistry and radioimmunoassay revealed that enkephalin peptides were being produced in releasable pools in sensory neurons innervating the treated skin area. Behavioral responses evoked by periodic sensitization and activation of C nociceptors innervating the vector-treated skin area revealed a substantial and long-lasting (at least 20 weeks) antihyperalgesic and analgesic effect limited to the areas to which the virus was applied. This approach may be a viable means of treating localized cutaneous burning pain and hyperalgesia.
Yeomans
David C
DC
Department of Anesthesia and Stanford Pain and Analgesia Research Center, Stanford University School of Medicine, Stanford, CA 94305-5117, USA. dcyeomans@stanford.edu
Lu
Ying
Y
Laurito
Charles E
CE
Peters
Michael C
MC
Vota-Vellis
Gina
G
Wilson
Steven P
SP
Pappas
George D
GD
D000698:Analgesia / Q000379:methods*; D000701:Analgesics, Opioid / Q000494:pharmacology; D000818:Animals; D001522:Behavior, Animal / Q000187:drug effects; D002211:Capsaicin / Q000494:pharmacology; D004195:Disease Models, Animal; D004745:Enkephalins / Q000134:cerebrospinal fluid / Q000235:genetics / Q000378:metabolism; D005727:Ganglia, Spinal / Q000737:chemistry / Q000378:metabolism; D015316:Genetic Therapy; D005822:Genetic Vectors / Q000008:administration & dosage*; D006930:Hyperalgesia / Q000139:chemically induced / Q000503:physiopathology / Q000628:therapy* / Q000821:virology*; D008251:Macaca; D009020:Morphine / Q000494:pharmacology; D009619:Nociceptors / Q000378:metabolism; D011930:Reaction Time / Q000235:genetics; D018139:Simplexvirus / Q000235:genetics*; D012867:Skin / Q000378:metabolism
D000701:Analgesics, Opioid; D004745:Enkephalins; D009020:Morphine; D002211:Capsaicin