Increased in vivo release of calcitonin gene-related peptide-like material from the spinal cord in arthritic rats.
Possible alterations in spinal systems containing calcitonin gene-related peptide (CGRP) due to polyarthritis were assessed in rats 3-4 weeks after an intradermal injection of Freund's adjuvant in the low back. The tissue levels of CGRP-like material (CGRPLM) were approximately 50% higher in the dorsal zone of the spinal cord and dorsal root ganglia at both the cervical and lumbar (but not thoracic) segments in polyarthritic rats than in age-paired control animals. In addition the rate of the spinal release of CGRPLM determined through an intrathecal perfusion procedure in halothane-anaesthetized animals was approximately 15-fold higher in polyarthritic rats than in controls. The blockade of mu-opioid receptors by intrathecal perfusion with 10 microM naloxone produced a larger increase in the spontaneous CGRPLM outflow in polyarthritic rats than in age-paired controls. Furthermore, the stimulation of mu-opioid receptors by intrathecal perfusion with 10 microM DAGO significantly inhibited the spinal outflow of CGRPLM only in polyarthritic rats. These data indicate that CGRP-containing primary afferent fibres are markedly activated in chronic suffering polyarthritic rats. This activation occurs in spite of an increased tonic inhibitory control by endogenous opioids acting at mu receptors.
Collin
E
E
INSERM (U 288), Neurobiologie Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, 75634 Paris, Cedex 13 France.
Mantelet
S
S
Frechilla
D
D
Pohl
M
M
Bourgoin
S
S
Hamon
M
M
Cesselin
F
F
D000700:Analgesics / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D015740:Calcitonin Gene-Related Peptide / Q000378:metabolism*; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D004745:Enkephalins / Q000494:pharmacology; D005727:Ganglia, Spinal / Q000187:drug effects / Q000378:metabolism; D007278:Injections, Spinal; D007457:Iodine Radioisotopes; D008297:Male; D009270:Naloxone / Q000494:pharmacology; D010477:Perfusion; D011863:Radioimmunoassay; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000187:drug effects / Q000378:metabolism; D013116:Spinal Cord / Q000187:drug effects / Q000378:metabolism*
D000700:Analgesics; D004745:Enkephalins; D007457:Iodine Radioisotopes; D017450:Receptors, Opioid, mu; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D009270:Naloxone; D015740:Calcitonin Gene-Related Peptide