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The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1.
Anesth Analg. 2008 Jun; 106(6):1890-6.A&A

Abstract

BACKGROUND

Tramadol is an effective analgesic substance widely used in medical practice. Its therapeutic action have been mainly attributed to the activation of mu-opioid receptors as well as to the inhibition of neurotransmitter reuptake mechanisms and various voltage- and ligand-gated ion channels of the nociceptive system. As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol.

METHODS

To achieve these goals, we used single-cell Ca-imaging as well as fluorescent image plate reader assays on Chinese hamster ovary (CHO) cells heterologously over-expressing TRPV1.

RESULTS

We found that (1) tramadol, similar to the well-known TRPV1 agonist, capsaicin, significantly increased [Ca(2+)](i) of TRPV1-CHO cells in a concentration-dependent fashion; (2) its effect was reversibly prevented by the TRPV1 antagonist capsazepine; (3) repeated application of tramadol resulted in marked tachyphylaxis; and (4) tramadol did not modify [Ca(2+)](i) in control (empty vector expressing) CHO cells.

CONCLUSIONS

Collectively, these findings strongly support the intriguing and novel concept that tramadol acts as an agonist of TRPV1. Considering that activation of TRPV1 on sensory neurons is followed by a local release of vasoactive neuropeptides and a marked desensitization of the afferent fibers (hence termination of pain sensation), our findings may equally explain both the desired analgesic as well as the often-seen, yet "unexpected," local side effects (e.g., initiation of burning pain and erythema) of tramadol.

Authors+Show Affiliations

Department of Physiology, University of Debrecen, Medical and Health Science Center, Research Center for Molecular Medicine, 4032 Debrecen, Hungary.No 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

18499628

Citation

Marincsák, Rita, et al. "The Analgesic Drug, Tramadol, Acts as an Agonist of the Transient Receptor Potential Vanilloid-1." Anesthesia and Analgesia, vol. 106, no. 6, 2008, pp. 1890-6.
Marincsák R, Tóth BI, Czifra G, et al. The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. Anesth Analg. 2008;106(6):1890-6.
Marincsák, R., Tóth, B. I., Czifra, G., Szabó, T., Kovács, L., & Bíró, T. (2008). The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. Anesthesia and Analgesia, 106(6), 1890-6. https://doi.org/10.1213/ane.0b013e318172fefc
Marincsák R, et al. The Analgesic Drug, Tramadol, Acts as an Agonist of the Transient Receptor Potential Vanilloid-1. Anesth Analg. 2008;106(6):1890-6. PubMed PMID: 18499628.
* Article titles in AMA citation format should be in sentence-case
TY - JOUR T1 - The analgesic drug, tramadol, acts as an agonist of the transient receptor potential vanilloid-1. AU - Marincsák,Rita, AU - Tóth,Balázs I, AU - Czifra,Gabriella, AU - Szabó,Tamás, AU - Kovács,László, AU - Bíró,Tamás, PY - 2008/5/24/pubmed PY - 2008/6/6/medline PY - 2008/5/24/entrez SP - 1890 EP - 6 JF - Anesthesia and analgesia JO - Anesth Analg VL - 106 IS - 6 N2 - BACKGROUND: Tramadol is an effective analgesic substance widely used in medical practice. Its therapeutic action have been mainly attributed to the activation of mu-opioid receptors as well as to the inhibition of neurotransmitter reuptake mechanisms and various voltage- and ligand-gated ion channels of the nociceptive system. As transient receptor potential vanilloid-1 (TRPV1, "the capsaicin receptor") has been shown to function as a central integrator molecule of pain sensation, our aim in the current study was to define the involvement of TRPV1 in the complex mechanism of action of tramadol. METHODS: To achieve these goals, we used single-cell Ca-imaging as well as fluorescent image plate reader assays on Chinese hamster ovary (CHO) cells heterologously over-expressing TRPV1. RESULTS: We found that (1) tramadol, similar to the well-known TRPV1 agonist, capsaicin, significantly increased [Ca(2+)](i) of TRPV1-CHO cells in a concentration-dependent fashion; (2) its effect was reversibly prevented by the TRPV1 antagonist capsazepine; (3) repeated application of tramadol resulted in marked tachyphylaxis; and (4) tramadol did not modify [Ca(2+)](i) in control (empty vector expressing) CHO cells. CONCLUSIONS: Collectively, these findings strongly support the intriguing and novel concept that tramadol acts as an agonist of TRPV1. Considering that activation of TRPV1 on sensory neurons is followed by a local release of vasoactive neuropeptides and a marked desensitization of the afferent fibers (hence termination of pain sensation), our findings may equally explain both the desired analgesic as well as the often-seen, yet "unexpected," local side effects (e.g., initiation of burning pain and erythema) of tramadol. SN - 1526-7598 UR - https://www.unboundmedicine.com/medline/citation/18499628/The_analgesic_drug_tramadol_acts_as_an_agonist_of_the_transient_receptor_potential_vanilloid_1_ L2 - https://doi.org/10.1213/ane.0b013e318172fefc DB - PRIME DP - Unbound Medicine ER -