freezing of enkephalinergic functions by multiple noxious foci a source of pain sensitization冻结enkephalinergic功能由多个有毒疫源地疼痛敏感的来源.pdfVIP

Freezing of Enkephalinergic Functions by Multiple Noxious Foci: A Source of Pain Sensitization? Franc¸ois Cesselin1,2*, Sylvie Bourgoin2,3, Annie Mauborgne1,2, Michel Hamon2,3, Daniel Le Bars1,2 ´ ´ ´ 1Team ‘‘Pain’’, INSERM UMRS 975, CNRS UMR 7225, Paris, France, 2 Universite Pierre et Marie Curie, Faculte de Medecine UPMC, Paris, France, 3 INSERM UMR 677, Paris, France 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. Methodology/Principal Findings: 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. Conclusion/Significance: 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. Citation: Cesselin F, Bourgoin S, Mauborgne A, Hamon M, Le Bars D (2009) Freezing of Enkephalinergic