Expression and G-protein coupling of mu-opioid receptors in the spinal cord and dorsal root ganglia of polyarthritic rats.
Although chronic inflammatory pain is known to be associated with hypersensitivity to mu opioid receptor agonists, no evidence for changes in the expression and/or characteristics of central mu opioid receptors has yet been reported in relevant models of this type of pain. In the present study, both immunohistochemical and autoradiographic approaches were used to address this question in polyarthritic rats, on the 4th week after intradermal injection of complete Freund's adjuvant, when inflammatory pain was at its maximum. Immunohistochemical labeling with specific anti-mu opioid receptor antibodies and autoradiographic labeling with [3H]DAMGO showed an upregulation of mu opioid receptors in the dorsal root ganglia but no changes in the density of these receptors in the dorsal horn at the level of L4-L6 segments in polyarthritic compared to age-paired control rats. On the other hand, autoradiographic quantification of the concentration-dependent increase in [35S]GTP-gamma-S binding by the mu-opioid receptor agonist DAMGO did not show any significant differences within the lumbar dorsal horn between polyarthritic and control rats. These data indicate that chronic inflammatory pain caused by polyarthritis was associated with an increased expression of mu-opioid receptors in dorsal root ganglion sensory neurones that did not result in an increased spinal density of these receptors, in spite of their well established axonal transport in the central portion of primary afferent fibres to the dorsal horn. In contrast, axonal transport of mu-opioid receptors in the peripheral portion of these fibres probably accounts for the increased receptor density in inflamed tissues already reported in the literature.
Ballet
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INSERM U288, NeuroPsychoPharmacologie Moléculaire, Cellulaire et Fonctionnelle, Faculté de Médecine Pitié-Salpêtrière, 91, Boulevard de l'Hôpital, 75634 Paris 13, France.
Conrath
M
M
Fischer
J
J
Kaneko
T
T
Hamon
M
M
Cesselin
F
F
D000701:Analgesics, Opioid / Q000378:metabolism / Q000494:pharmacology; D000818:Animals; D001169:Arthritis, Experimental / Q000378:metabolism*; D001345:Autoradiography; D002908:Chronic Disease; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)- / Q000378:metabolism / Q000494:pharmacology; D019204:GTP-Binding Proteins / Q000378:metabolism*; D005727:Ganglia, Spinal / Q000378:metabolism*; D016244:Guanosine 5'-O-(3-Thiotriphosphate) / Q000378:metabolism / Q000494:pharmacology; D008159:Lumbar Vertebrae; D008297:Male; D010146:Pain / Q000378:metabolism; D051381:Rats; D017207:Rats, Sprague-Dawley; D017450:Receptors, Opioid, mu / Q000378:metabolism*; D013116:Spinal Cord / Q000378:metabolism*; D013462:Sulfur Radioisotopes; D014316:Tritium
D000701:Analgesics, Opioid; D017450:Receptors, Opioid, mu; D013462:Sulfur Radioisotopes; D014316:Tritium; D020875:Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; D016244:Guanosine 5'-O-(3-Thiotriphosphate); D019204:GTP-Binding Proteins