![[Feedback]](/icons/banner/feedbackACT.gif){kind=icon}
![[For Subscribers]](/icons/banner/subscriberACT.gif){kind=icon}
![[Archive]](/icons/banner/archiveACT.gif){kind=icon}
![[Search]](/icons/banner/searchACT.gif){kind=icon}
![[Contents]](/icons/banner/tocACT.gif){kind=icon}
|
|
|
|
|
||
Klinik für Anaesthesiologie und Operative Intensivmedizin, Freie Universität Berlin, Berlin, Germany
Opioids mediate their analgesic effects by activating µ-opioid receptors (MOR) not only within the central nervous system but also on peripheral sensory neurons. The peripheral analgesic effects of opioids are best described under inflammatory conditions (e.g., arthritis). The present study investigated the effects of inflammation on MOR binding and G-protein coupling of full versus partial MOR agonists in dorsal root ganglia (DRG) of primary afferent neurons. Our results show that Freund's complete adjuvant (FCA) unilateral hindpaw inflammation induces a significant up-regulation of MOR binding sites (25 to 47 fmol/mg of protein) on DRG membranes without affecting the affinity of either full or partial MOR agonists. In our immunohistochemical studies, the number of MOR-immunoreactive neurons consistently increased. This increase was mostly caused by small-diameter nociceptive DRG neurons. The full agonist DAMGO induced MOR G-protein coupling in DRG of animals without FCA inflammation (EC50 = 56 nM; relative Emax = 100%). FCA inflammation resulted in significant increases in DAMGO-induced MOR G-protein coupling (EC50 = 29 nM; relative Emax = 145%). The partial agonist buprenorphine hydrochloride (BUP) showed no detectable G-protein coupling in DRG of animals without FCA inflammation; however, partial agonist activity of BUP-induced MOR G-protein coupling was detectable in animals with FCA inflammation (EC50 = 1.6 nM; relative Emax = 82%). In behavioral studies, administration of BUP produced significant antinociception only in inflamed but not in noninflamed paws. These findings show that inflammation causes changes in MOR binding and G-protein coupling in primary afferent neurons. They further underscore the important differences in clinical studies testing peripherally active opioids in inflammatory painful conditions.
Address correspondence to: Dr. Christian Zöllner, Klinik für Anaesthesiologie und operative Intensivmedizin, Freie Universität Berlin, Universitätklinikum Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany. E-mail: zoellner{at}zop-admin.ukbf.fu-berlin.de
This article has been cited by other articles:
|
|
 |
|
  K. T. Sykes, S. R. White, R. W. Hurley, H. Mizoguchi, L. F. Tseng, and D. L. Hammond Mechanisms Responsible for the Enhanced Antinociceptive Effects of {micro}-Opioid Receptor Agonists in the Rostral Ventromedial Medulla of Male Rats with Persistent Inflammatory Pain J. Pharmacol. Exp. Ther., August 1, 2007; 322(2): 813 - 821. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A Mousa, R. H Straub, M. Schafer, and C. Stein {beta}-Endorphin, Met-enkephalin and corresponding opioid receptors within synovium of patients with joint trauma, osteoarthritis and rheumatoid arthritis Ann Rheum Dis, July 1, 2007; 66(7): 871 - 879. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. A. Berg, A. M. Patwardhan, T. A. Sanchez, Y. M. Silva, K. M. Hargreaves, and W. P. Clarke Rapid Modulation of {micro}-Opioid Receptor Signaling in Primary Sensory Neurons J. Pharmacol. Exp. Ther., June 1, 2007; 321(3): 839 - 847. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 S. A. Mousa, B. P. Cheppudira, M. Shaqura, O. Fischer, J. Hofmann, R. Hellweg, and M. Schafer Nerve growth factor governs the enhanced ability of opioids to suppress inflammatory pain Brain, February 1, 2007; 130(2): 502 - 513. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. Endres-Becker, P. A. Heppenstall, S. A. Mousa, D. Labuz, A. Oksche, M. Schafer, C. Stein, and C. Zollner {micro}-Opioid Receptor Activation Modulates Transient Receptor Potential Vanilloid 1 (TRPV1) Currents in Sensory Neurons in A Model of Inflammatory Pain Mol. Pharmacol., January 1, 2007; 71(1): 12 - 18. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 X. Wang, R. J. Traub, and A. Z. Murphy Persistent pain model reveals sex difference in morphine potency Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R300 - R306. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
Y. Ji, A. Z. Murphy, and R. J. Traub Sex differences in morphine-induced analgesia of visceral pain are supraspinally and peripherally mediated Am J Physiol Regulatory Integrative Comp Physiol, August 1, 2006; 291(2): R307 - R314. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 T. D. Plant, C. Zollner, S. A. Mousa, and A. Oksche Endothelin-1 Potentiates Capsaicin-Induced TRPV1 Currents Via the Endothelin A Receptor. Experimental Biology and Medicine, June 1, 2006; 231(6): 1161 - 1164. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 D. Labuz, S. Berger, S. A. Mousa, C. Zollner, H. L. Rittner, M. A. Shaqura, T. Segovia-Silvestre, B. Przewlocka, C. Stein, and H. Machelska Peripheral antinociceptive effects of exogenous and immune cell-derived endomorphins in prolonged inflammatory pain. J. Neurosci., April 19, 2006; 26(16): 4350 - 4358. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. N. Wenk, J.-D. Brederson, and C. N. Honda Morphine Directly Inhibits Nociceptors in Inflamed Skin J Neurophysiol, April 1, 2006; 95(4): 2083 - 2097. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
I. Bileviciute-Ljungar, M. Spetea, Y. Guo, J. Schutz, P. Windisch, and H. Schmidhammer Peripherally Mediated Antinociception of the {micro}-Opioid Receptor Agonist 2-[(4,5{alpha}-Epoxy-3-hydroxy-14beta-methoxy-17-methylmorphinan-6beta-yl)amino]acetic Acid (HS-731) after Subcutaneous and Oral Administration in Rats with Carrageenan-Induced Hindpaw Inflammation J. Pharmacol. Exp. Ther., April 1, 2006; 317(1): 220 - 227. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 H. L. Rittner, H. Machelska, and C. Stein Leukocytes in the regulation of pain and analgesia J. Leukoc. Biol., December 1, 2005; 78(6): 1215 - 1222. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Whiteside, J. M. Boulet, and K. Walker The Role of Central and Peripheral {micro} Opioid Receptors in Inflammatory Pain and Edema: A Study Using Morphine and DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triaza-spiro[4.5]dec-3-yl]-acetic Acid) J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1234 - 1240. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
C. D. Cook and M. D. Nickerson Nociceptive Sensitivity and Opioid Antinociception and Antihyperalgesia in Freund's Adjuvant-Induced Arthritic Male and Female Rats J. Pharmacol. Exp. Ther., April 1, 2005; 313(1): 449 - 459. [Abstract] [Full Text] [PDF]
|
|
|
|
 |
|
 J. P. Williams and D. G. Lambert Editorial II: Opioids and the neuroimmune axis Br. J. Anaesth., January 1, 2005; 94(1): 3 - 6. [Full Text] [PDF]
|
|
|
|
|
|
C. Borner, J. Kraus, H. Schroder, H. Ammer, and V. Hollt Transcriptional Regulation of the Human {micro}-Opioid Receptor Gene by Interleukin-6 Mol. Pharmacol., December 1, 2004; 66(6): 1719 - 1726. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
E. R. Butelman, T. J. Harris, and M. J. Kreek Antiallodynic Effects of Loperamide and Fentanyl against Topical Capsaicin-Induced Allodynia in Unanesthetized Primates J. Pharmacol. Exp. Ther., October 1, 2004; 311(1): 155 - 163. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
R. Likar, S. A. Mousa, G. Philippitsch, H. Steinkellner, W. Koppert, C. Stein, and M. Schafer Increased numbers of opioid expressing inflammatory cells do not affect intra-articular morphine analgesia Br. J. Anaesth., September 1, 2004; 93(3): 375 - 380. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
K. J. Valenzano, W. Miller, Z. Chen, S. Shan, G. Crumley, S. F. Victory, E. Davies, J.-C. Huang, N. Allie, S. J. Nolan, et al. DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic Acid), a Novel, Systemically Available, and Peripherally Restricted Mu Opioid Agonist with Antihyperalgesic Activity: I. In Vitro Pharmacological Characterization and Pharmacokinetic Properties J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 783 - 792. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
G. T. Whiteside, J. E. Harrison, M. S. Pearson, Z. Chen, Y. Rotshteyn, P. I. Turchin, J. D. Pomonis, L. Mark, K. Walker, and K. C. Brogle DiPOA ([8-(3,3-Diphenyl-propyl)-4-oxo-1-phenyl-1,3,8-triazaspiro[4.5]dec-3-yl]-acetic Acid), a Novel, Systemically Available, and Peripherally Restricted Mu Opioid Agonist with Antihyperalgesic Activity: II. In Vivo Pharmacological Characterization in the Rat J. Pharmacol. Exp. Ther., August 1, 2004; 310(2): 793 - 799. [Abstract] [Full Text] [PDF]
|
|
|
|
|
|
M. A. Shaqura, C. Zollner, S. A. Mousa, C. Stein, and M. Schafer Characterization of {micro} Opioid Receptor Binding and G Protein Coupling in Rat Hypothalamus, Spinal Cord, and Primary Afferent Neurons during Inflammatory Pain J. Pharmacol. Exp. Ther., February 1, 2004; 308(2): 712 - 718. [Abstract] [Full Text] [PDF]
|
|
 |
 |
 |
|
 |
 |
 |
