QUICK SEARCH:   [advanced] Author: Keyword(s): Year:  Vol:  Page:

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

This Article Full Text Full Text (PDF) Submit an eLetter Alert me when this article is cited Alert me when eLetters are posted Alert me if a correction is posted Citation Map Services Email this article to a friend Similar articles in this journal Similar articles in Web of Science Similar articles in PubMed Alert me to new issues of the journal Download to citation manager Citing Articles Citing Articles via HighWire Citing Articles via Web of Science (26) Citing Articles via Google Scholar Google Scholar Articles by Silbert, S. C. Articles by McCleskey, E. W. Search for Related Content PubMed PubMed Citation Articles by Silbert, S. C. Articles by McCleskey, E. W.

 Previous Article  |  Next Article 

The Journal of Neuroscience, January 1, 2003, 23(1):34-42

Quantitative Single-Cell Differences in µ-Opioid Receptor mRNA Distinguish Myelinated and Unmyelinated Nociceptors

Seth C. Silbert, Daniel W. Beacham, and Edwin W. McCleskey

Vollum Institute, Oregon Health and Science University, Portland, Oregon 97239

A remarkable feature of opioids is that they inhibit pain that persists from previous injuries without eliminating either the initial pain of a new injury or the protective reflexes triggered by it. Here we ask whether selective expression of the µ-opioid receptor (MOR) gene in primary nociceptors (pain-sensing neurons) might contribute to this aspect of opioid specificity. We quantified single-cell levels of MOR mRNA and measured opioid inhibition of Ca channels on identified nociceptors and low-threshold mechanosensors (non-nociceptors) isolated from rats. Negligibly few non-nociceptors express MOR mRNA, thereby rendering nonpain sensations insensitive to opioids. Nearly half of nociceptors of all size classes also fail to express MOR mRNA or to respond to opioids. Among the opioid-responsive nociceptors, a gene dose-response relationship exists such that maximal opioid inhibition occurs when the MOR mRNA concentration of a cell is >15 pM. Almost all large, myelinated nociceptors express MOR mRNA below this level, whereas small, unmyelinated nociceptors are likely to express above it. Because myelinated nociceptors mediate anti-nociceptive reflexes, the data suggest that fine control of the MOR mRNA level contributes to a complex neural trait: the ability of opioids to suppress persistent pain without preventing response to a new injury.

Key words: opioid receptors; opiates; nociceptors; sensory neurons; pain; analgesia; calcium channels; single-cell PCR

---

Copyright © 2003 Society for Neuroscience  0270-6474/03/23134-09$05.00/0

This article has been cited by other articles:

				G. Dussor, M. J. Zylka, D. J. Anderson, and E. W. McCleskey Cutaneous Sensory Neurons Expressing the Mrgprd Receptor Sense Extracellular ATP and Are Putative Nociceptors J Neurophysiol, April 1, 2008; 99(4): 1581 - 1589. [Abstract] [Full Text] [PDF]

				Z. Fang, C.-K. Park, H. Y. Li, H. Y. Kim, S.-H. Park, S. J. Jung, J. S. Kim, A. Monteil, S. B. Oh, and R. J. Miller Molecular Basis of Cav2.3 Calcium Channels in Rat Nociceptive Neurons J. Biol. Chem., February 16, 2007; 282(7): 4757 - 4764. [Abstract] [Full Text] [PDF]

				C.-K. Park, M. S. Kim, Z. Fang, H. Y. Li, S. J. Jung, S.-Y. Choi, S. J. Lee, K. Park, J. S. Kim, and S. B. Oh Functional Expression of Thermo-transient Receptor Potential Channels in Dental Primary Afferent Neurons: IMPLICATION FOR TOOTH PAIN J. Biol. Chem., June 23, 2006; 281(25): 17304 - 17311. [Abstract] [Full Text] [PDF]

				A. Wagatsuma, H. Sadamoto, T. Kitahashi, K. Lukowiak, A. Urano, and E. Ito Determination of the exact copy numbers of particular mRNAs in a single cell by quantitative real-time RT-PCR J. Exp. Biol., June 15, 2005; 208(12): 2389 - 2398. [Abstract] [Full Text] [PDF]

				Z.-Z. Wu, S.-R. Chen, and H.-L. Pan Differential Sensitivity of N- and P/Q-Type Ca2+ Channel Currents to a {micro} Opioid in Isolectin B -Positive and -Negative Dorsal Root Ganglion Neurons J. Pharmacol. Exp. Ther., December 1, 2004; 311(3): 939 - 947. [Abstract] [Full Text] [PDF]

				S. M. Todorovic, S. Pathirathna, B. C. Brimelow, M. M. Jagodic, S.-H. Ko, X. Jiang, K. R. Nilsson, C. F. Zorumski, D. F. Covey, and V. Jevtovic-Todorovic 5{beta}-Reduced Neuroactive Steroids Are Novel Voltage-Dependent Blockers of T-Type Ca2+ Channels in Rat Sensory Neurons in Vitro and Potent Peripheral Analgesics in Vivo Mol. Pharmacol., November 1, 2004; 66(5): 1223 - 1235. [Abstract] [Full Text] [PDF]

				I. A. Khasabova, C. Harding-Rose, D. A. Simone, and V. S. Seybold Differential Effects of CB1 and Opioid Agonists on Two Populations of Adult Rat Dorsal Root Ganglion Neurons J. Neurosci., February 18, 2004; 24(7): 1744 - 1753. [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]

				Y. Xu, Y. Gu, G.-Y. Xu, P. Wu, G.-W. Li, and L.-Y. M. Huang Adeno-associated viral transfer of opioid receptor gene to primary sensory neurons: A strategy to increase opioid antinociception PNAS, May 13, 2003; 100(10): 6204 - 6209. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help