title: Freezing of enkephalinergic functions by multiple noxious foci: a source of pain sensitization?
abstract: BACKGROUND
  The functional significance of proenkephalin systems in processing pain remains an open question and indeed is puzzling. For example, a noxious mechanical stimulus does not alter the release of Met-enkephalin-like material (MELM) from segments of the spinal cord related to the stimulated area of the body, but does increase its release from other segments.
  
  
  RESULTS
  Here we show that, in the rat, a noxious mechanical stimulus applied to either the right or the left hind paw elicits a marked increase of MELM release during perifusion of either the whole spinal cord or the cervico-trigeminal area. However, these stimulatory effects were not additive and indeed, disappeared completely when the right and left paws were stimulated simultaneously.
  
  
  CONCLUSIONS
  We have concluded that in addition to the concept of a diffuse control of the transmission of nociceptive signals through the dorsal horn, there is a diffuse control of the modulation of this transmission. The "freezing" of Met-enkephalinergic functions represents a potential source of central sensitization in the spinal cord, notably in clinical situations involving multiple painful foci, e.g. cancer with metastases, poly-traumatism or rheumatoid arthritis.
authors.affiliation: Team Pain, INSERM UMRS 975, CNRS UMR 7225, Paris, France. francois.cesselin@upmc.fr
authors.forename: François
authors.initials: F
authors.lastname: Cesselin
authors.forename: Sylvie
authors.initials: S
authors.lastname: Bourgoin
authors.forename: Annie
authors.initials: A
authors.lastname: Mauborgne
authors.forename: Michel
authors.initials: M
authors.lastname: Hamon
authors.forename: Daniel
authors.initials: D
authors.lastname: Le Bars
mesh_terms: D000818:Animals; D004744:Enkephalin, Methionine / Q000378:metabolism*; D004745:Enkephalins / Q000378:metabolism; D005121:Extremities; D008297:Male; D009433:Neural Inhibition; D010146:Pain / Q000503:physiopathology*; D011498:Protein Precursors / Q000378:metabolism; D011817:Rabbits; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000503:physiopathology; D014275:Trigeminal Caudal Nucleus / Q000378:metabolism*; D014279:Trigeminal Nucleus, Spinal / Q000378:metabolism
chemical_list: D004745:Enkephalins; D011498:Protein Precursors; C029992:proenkephalin; D004744:Enkephalin, Methionine