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High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors.
Mol Pain. 2009 Apr 16; 5:17.MP

Abstract

BACKGROUND

Morphine and its derivatives are key drugs in pain control. Despite its well-known analgesic properties morphine at high concentrations may be proalgesic. Particularly, short-lasting painful sensations have been reported upon dermal application of morphine. To study a possible involvement of TRP receptors in the pro-nociceptive effects of morphine (0.3 - 10 mM), two models of nociception were employed using C57BL/6 mice and genetically related TRPV1 and TRPA1 knockout animals, which were crossed and generated double knockouts. Hindpaw skin flaps were used to investigate the release of calcitonin gene-related peptide indicative of nociceptive activation.

RESULTS

Morphine induced release of calcitonin gene-related peptide and sensitized the release evoked by heat or the TRPA1 agonist acrolein. Morphine activated HEK293t cells transfected with TRPV1 or TRPA1. Activation of C57BL/6 mouse dorsal root ganglion neurons in culture was investigated with calcium imaging. Morphine induced a dose-dependent rise in intracellular calcium in neurons from wild-type animals. In neurons from TRPV1 and TRPA1 knockout animals activation by morphine was markedly reduced, in the TRPV1/A1 double knockout animals this morphine effect was abrogated. Naloxone induced an increase in calcium levels similar to morphine. The responses to both morphine and naloxone were sensitized by bradykinin.

CONCLUSION

Nociceptor activation and sensitization by morphine is conveyed by TRPV1 and TRPA1.

Authors+Show Affiliations

Institute of Physiology and Pathophysiology, University of Erlangen-Nürnberg, Universitätsstrasse 17, Erlangen, 91054 Germany. aforster@physiologie1.uni-erlangen.deNo affiliation info availableNo affiliation info availableNo affiliation info available

Pub Type(s)

Journal Article

Language

eng

PubMed ID

19371406

Citation

Forster, Alexander B., et al. "High Concentrations of Morphine Sensitize and Activate Mouse Dorsal Root Ganglia Via TRPV1 and TRPA1 Receptors." Molecular Pain, vol. 5, 2009, p. 17.
Forster AB, Reeh PW, Messlinger K, et al. High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors. Mol Pain. 2009;5:17.
Forster, A. B., Reeh, P. W., Messlinger, K., & Fischer, M. J. (2009). High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors. Molecular Pain, 5, 17. https://doi.org/10.1186/1744-8069-5-17
Forster AB, et al. High Concentrations of Morphine Sensitize and Activate Mouse Dorsal Root Ganglia Via TRPV1 and TRPA1 Receptors. Mol Pain. 2009 Apr 16;5:17. PubMed PMID: 19371406.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - High concentrations of morphine sensitize and activate mouse dorsal root ganglia via TRPV1 and TRPA1 receptors. AU - Forster,Alexander B, AU - Reeh,Peter W, AU - Messlinger,Karl, AU - Fischer,Michael J M, Y1 - 2009/04/16/ PY - 2009/01/13/received PY - 2009/04/16/accepted PY - 2009/4/18/entrez PY - 2009/4/18/pubmed PY - 2009/6/25/medline SP - 17 EP - 17 JF - Molecular pain JO - Mol Pain VL - 5 N2 - BACKGROUND: Morphine and its derivatives are key drugs in pain control. Despite its well-known analgesic properties morphine at high concentrations may be proalgesic. Particularly, short-lasting painful sensations have been reported upon dermal application of morphine. To study a possible involvement of TRP receptors in the pro-nociceptive effects of morphine (0.3 - 10 mM), two models of nociception were employed using C57BL/6 mice and genetically related TRPV1 and TRPA1 knockout animals, which were crossed and generated double knockouts. Hindpaw skin flaps were used to investigate the release of calcitonin gene-related peptide indicative of nociceptive activation. RESULTS: Morphine induced release of calcitonin gene-related peptide and sensitized the release evoked by heat or the TRPA1 agonist acrolein. Morphine activated HEK293t cells transfected with TRPV1 or TRPA1. Activation of C57BL/6 mouse dorsal root ganglion neurons in culture was investigated with calcium imaging. Morphine induced a dose-dependent rise in intracellular calcium in neurons from wild-type animals. In neurons from TRPV1 and TRPA1 knockout animals activation by morphine was markedly reduced, in the TRPV1/A1 double knockout animals this morphine effect was abrogated. Naloxone induced an increase in calcium levels similar to morphine. The responses to both morphine and naloxone were sensitized by bradykinin. CONCLUSION: Nociceptor activation and sensitization by morphine is conveyed by TRPV1 and TRPA1. SN - 1744-8069 UR - https://www.unboundmedicine.com/medline/citation/19371406/High_concentrations_of_morphine_sensitize_and_activate_mouse_dorsal_root_ganglia_via_TRPV1_and_TRPA1_receptors_ L2 - https://journals.sagepub.com/doi/10.1186/1744-8069-5-17?url_ver=Z39.88-2003&rfr_id=ori:rid:crossref.org&rfr_dat=cr_pub=pubmed DB - PRIME DP - Unbound Medicine ER -