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Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain.
Mol Pharmacol. 2007 Jan; 71(1):12-8.MP

Abstract

Current therapy for inflammatory pain includes the peripheral application of opioid receptor agonists. Activation of opioid receptors modulates voltage-gated ion channels, but it is unclear whether opioids can also influence ligand-gated ion channels [e.g., the transient receptor potential vanilloid type 1 (TRPV1)]. TRPV1 channels are involved in the development of thermal hypersensitivity associated with tissue inflammation. In this study, we investigated mu-opioid receptor and TRPV1 expression in primary afferent neurons in the dorsal root ganglion (DRG) in complete Freund's adjuvant (CFA)-induced paw inflammation. In addition, the present study examined whether the activity of TRPV1 in DRG neurons can be inhibited by mu-opioid receptor (mu-receptor) ligands and whether this inhibition is increased after CFA inflammation. Immunohistochemistry demonstrated colocalization of TRPV1 and mu-receptors in DRG neurons. CFA-induced inflammation increased significantly the number of TRPV1- and mu-receptor-positive DRG neurons, as well as TRPV1 binding sites. In whole-cell patch clamp studies, opioids significantly decreased capsaicin-induced TRPV1 currents in a naloxone- and pertussis toxinsensitive manner. The inhibitory effect of morphine on TRPV1 was abolished by forskolin and 8-bromo-cAMP. During inflammation, an increase in TRPV1 is apparently rivaled by an increase of mu-receptors. However, in single dissociated DRG neurons, the inhibitory effects of morphine are not different between animals with and without CFA inflammation. In in vivo experiments, we found that locally applied morphine reduced capsaicin-induced thermal allodynia. In summary, our results indicate that mu-receptor activation can inhibit the activity of TRPV1 via G(i/o) proteins and the cAMP pathway. These observations demonstrate an important new mechanism underlying the analgesic efficacy of peripherally acting mu-receptor ligands in inflammatory pain.

Authors+Show Affiliations

Klinik für Anaesthesiologie und operative Intensivmedizin, Charité-Universitätsmedizin Berlin, Campus Benjamin Franklin, Hindenburgdamm 30, 12200 Berlin, Germany.No affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article
Research Support, Non-U.S. Gov't

Language

eng

PubMed ID

17005903

Citation

Endres-Becker, Jeannette, et al. "Mu-opioid Receptor Activation Modulates Transient Receptor Potential Vanilloid 1 (TRPV1) Currents in Sensory Neurons in a Model of Inflammatory Pain." Molecular Pharmacology, vol. 71, no. 1, 2007, pp. 12-8.
Endres-Becker J, Heppenstall PA, Mousa SA, et al. Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Mol Pharmacol. 2007;71(1):12-8.
Endres-Becker, J., Heppenstall, P. A., Mousa, S. A., Labuz, D., Oksche, A., Schäfer, M., Stein, C., & Zöllner, C. (2007). Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. Molecular Pharmacology, 71(1), 12-8.
Endres-Becker J, et al. Mu-opioid Receptor Activation Modulates Transient Receptor Potential Vanilloid 1 (TRPV1) Currents in Sensory Neurons in a Model of Inflammatory Pain. Mol Pharmacol. 2007;71(1):12-8. PubMed PMID: 17005903.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - Mu-opioid receptor activation modulates transient receptor potential vanilloid 1 (TRPV1) currents in sensory neurons in a model of inflammatory pain. AU - Endres-Becker,Jeannette, AU - Heppenstall,Paul A, AU - Mousa,Shaaban A, AU - Labuz,Dominika, AU - Oksche,Alexander, AU - Schäfer,Michael, AU - Stein,Christoph, AU - Zöllner,Christian, Y1 - 2006/09/27/ PY - 2006/9/29/pubmed PY - 2007/2/3/medline PY - 2006/9/29/entrez SP - 12 EP - 8 JF - Molecular pharmacology JO - Mol Pharmacol VL - 71 IS - 1 N2 - Current therapy for inflammatory pain includes the peripheral application of opioid receptor agonists. Activation of opioid receptors modulates voltage-gated ion channels, but it is unclear whether opioids can also influence ligand-gated ion channels [e.g., the transient receptor potential vanilloid type 1 (TRPV1)]. TRPV1 channels are involved in the development of thermal hypersensitivity associated with tissue inflammation. In this study, we investigated mu-opioid receptor and TRPV1 expression in primary afferent neurons in the dorsal root ganglion (DRG) in complete Freund's adjuvant (CFA)-induced paw inflammation. In addition, the present study examined whether the activity of TRPV1 in DRG neurons can be inhibited by mu-opioid receptor (mu-receptor) ligands and whether this inhibition is increased after CFA inflammation. Immunohistochemistry demonstrated colocalization of TRPV1 and mu-receptors in DRG neurons. CFA-induced inflammation increased significantly the number of TRPV1- and mu-receptor-positive DRG neurons, as well as TRPV1 binding sites. In whole-cell patch clamp studies, opioids significantly decreased capsaicin-induced TRPV1 currents in a naloxone- and pertussis toxinsensitive manner. The inhibitory effect of morphine on TRPV1 was abolished by forskolin and 8-bromo-cAMP. During inflammation, an increase in TRPV1 is apparently rivaled by an increase of mu-receptors. However, in single dissociated DRG neurons, the inhibitory effects of morphine are not different between animals with and without CFA inflammation. In in vivo experiments, we found that locally applied morphine reduced capsaicin-induced thermal allodynia. In summary, our results indicate that mu-receptor activation can inhibit the activity of TRPV1 via G(i/o) proteins and the cAMP pathway. These observations demonstrate an important new mechanism underlying the analgesic efficacy of peripherally acting mu-receptor ligands in inflammatory pain. SN - 0026-895X UR - https://www.unboundmedicine.com/medline/citation/17005903/Mu_opioid_receptor_activation_modulates_transient_receptor_potential_vanilloid_1__TRPV1__currents_in_sensory_neurons_in_a_model_of_inflammatory_pain_ L2 - http://molpharm.aspetjournals.org/cgi/pmidlookup?view=long&pmid=17005903 DB - PRIME DP - Unbound Medicine ER -