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

HOME  |   SEARCH  |   ARCHIVE  |   SUBSCRIBE  |   CONTACT  |   HELP

The Journal of Neuroscience, April 6, 2005, 25(14):3651-3660; doi:10.1523/JNEUROSCI.0252-05.2005

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 (21) Citing Articles via Google Scholar Google Scholar Articles by Kondo, I. Articles by Yaksh, T. L. Search for Related Content PubMed PubMed Citation Articles by Kondo, I. Articles by Yaksh, T. L.

 Previous Article  |  Next Article 

Behavioral/Systems/Cognitive
Inhibition by Spinal µ- and -Opioid Agonists of Afferent-Evoked Substance P Release

Ichiro Kondo,¹ Juan Carlos G. Marvizon,³ Bingbing Song,³ Frances Salgado,¹ Simone Codeluppi,^2,4 Xiao-Ying Hua,¹ and Tony L. Yaksh¹

Departments of ¹Anesthesiology and ²Pathology, University of California-San Diego, La Jolla, California 92093, ³Center for Neurovisceral Sciences and Women's Health, Department of Medicine, David Geffen School of Medicine at University of California-Los Angeles, Los Angeles, California 90073, and ⁴The Burnham Institute, La Jolla, California 92037

Opioid µ- and -receptors are present on the central terminals of primary afferents, where they are thought to inhibit neurotransmitter release. This mechanism may mediate analgesia produced by spinal opiates; however, when they used neurokinin 1 receptor (NK1R) internalization as an indicator of substance P release, Trafton et al. (1999) noted that this evoked internalization was altered only modestly by morphine delivered intrathecally at spinal cord segment S1-S2. We reexamined this issue by studying the effect of opiates on NK1R internalization in spinal cord slices and in vivo. In slices, NK1R internalization evoked by dorsal root stimulation at C-fiber intensity was abolished by the µ agonist [D-Ala², N-Me-Phe⁴, Gly-ol⁵]-enkephalin (DAMGO) (1 µM) and decreased by the agonist [D-Phe^2,5]-enkephalin (DPDPE) (1 µM). In vivo, hindpaw compression induced NK1R internalization in ipsilateral laminas I-II. This evoked internalization was significantly reduced by morphine (60 nmol), DAMGO (1 nmol), and DPDPE (100 nmol), but not by the agonist trans-(1S,2S)-3,4-dichloro-N-mathyl-N-[2-(1-pyrrolidinyl)cyclohexyl]-benzeneacetamide hydrochloride (200 nmol), delivered at spinal cord segment L2 using intrathecal catheters. These doses of the µ and agonists were equi-analgesic as measured by a thermal escape test. Lower doses neither produced analgesia nor inhibited NK1R internalization. In contrast, morphine delivered by percutaneous injections at S1-S2 had only a modest effect on thermal escape, even at higher doses. Morphine decreased NK1R internalization after systemic delivery, but at a dose greater than that necessary to produce equivalent analgesia. All effects were reversed by naloxone. These results indicate that lumbar opiates inhibit noxious stimuli-induced neurotransmitter release from primary afferents at doses that are confirmed behaviorally as analgesic.

Key words: C-fibers; dorsal horn; internalization; neurokinin; morphine; spinal cord

---

Received Aug 12, 2004; revised February 24, 2005; accepted February 24, 2005.

This article has been cited by other articles:

				M. Tramullas, A. Lantero, A. Diaz, N. Morchon, D. Merino, A. Villar, D. Buscher, R. Merino, J. M. Hurle, J. C. Izpisua-Belmonte, et al. BAMBI (Bone Morphogenetic Protein and Activin Membrane-Bound Inhibitor) Reveals the Involvement of the Transforming Growth Factor-{beta} Family in Pain Modulation J. Neurosci., January 27, 2010; 30(4): 1502 - 1511. [Abstract] [Full Text] [PDF]

				S. C. Brock and C. R. Tonussi Intrathecally Injected Morphine Inhibits Inflammatory Paw Edema: The Involvement of Nitric Oxide and Cyclic-Guanosine Monophosphate Anesth. Analg., March 1, 2008; 106(3): 965 - 971. [Abstract] [Full Text] [PDF]

				R. H. Kline IV and R. G. Wiley Spinal {micro}-Opioid Receptor-Expressing Dorsal Horn Neurons: Role in Nociception and Morphine Antinociception J. Neurosci., January 23, 2008; 28(4): 904 - 913. [Abstract] [Full Text] [PDF]

				D. Blivis, G. Z. Mentis, M. J. O'Donovan, and A. Lev-Tov Differential Effects of Opioids on Sacrocaudal Afferent Pathways and Central Pattern Generators in the Neonatal Rat Spinal Cord J Neurophysiol, April 1, 2007; 97(4): 2875 - 2886. [Abstract] [Full Text] [PDF]

				J. A. DeLeo Basic Science of Pain J. Bone Joint Surg. Am., April 1, 2006; 88(suppl_2): 58 - 62. [Abstract] [Full Text] [PDF]

				G. Gu, I. Kondo, X.-Y. Hua, and T. L. Yaksh Resting and Evoked Spinal Substance P Release during Chronic Intrathecal Morphine Infusion: Parallels with Tolerance and Dependence J. Pharmacol. Exp. Ther., September 1, 2005; 314(3): 1362 - 1369. [Abstract] [Full Text] [PDF]

Home  |   Search  |   Archive  |   Subscribe  |   Contact  |   Help