Why Labor Epidural Causes Fever and Why Lidocaine Burns on Injection? Role of TRPV 1 Receptor in Hyperthermia: Possible Explanation of Mechanism of Hyperthermia during Labor Epidural and Burning Sensation on Injection of Local Anesthetics


The mechanisms of epidural-associated fever remain incompletely understood [1-3]. We propose that action of local anesthetic on TPRV1. The transient receptor potential cation channel subfamily V member 1 (TRPV1), also known as the capsaicin receptor and the vanilloid receptor can explain this effect and explain mechanism of burning sensation on local anesthetic injected subcutaneously or intramuscular. Role of TRPV1 receptor was not discussed previously in Obstetric Anesthesia literature. Based on available data, we propose that Local Anesthetics work as agonist/antagonist on TPRV1 receptors. Antagonist action may cause hyperthermia through modifying thermoregulation [4], agonist action may cause hyperthermia thru release of IL-6 and other mediators of inflammation [5-10]. Agonist action may explain burning sensation on injection of Local Anesthetics. Burning sensation can be diminished by increasing pH of Local Anesthetic solution, because vanillin receptors are stimulated by acidification through lower pH [11,12].

Share and Cite:

I. Kozlov, "Why Labor Epidural Causes Fever and Why Lidocaine Burns on Injection? Role of TRPV 1 Receptor in Hyperthermia: Possible Explanation of Mechanism of Hyperthermia during Labor Epidural and Burning Sensation on Injection of Local Anesthetics," Open Journal of Anesthesiology, Vol. 2 No. 4, 2012, pp. 134-137. doi: 10.4236/ojanes.2012.24030.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] S. Segal, “Labor Epidural Analgesia and Maternal Fever,” Anesthesia & Analgesia, Vol. 111, No. 6, 2010, pp. 14671475. doi:10.1213/ANE.0b013e3181f713d4
[2] L. Goetzl, “Epidural Analgesia and Maternal Fever: A Clinical and Research Update,” Current Opinion in Anesthesiology, Vol. 25, No. 3, 2012, pp. 292-299. doi:10.1097/ACO.0b013e3283530d7c
[3] S. Shatken, K. Greenough and C. McPherson, “Epidural Fever and Its Implications for Mothers and Neonates: Taking the Heat,” Journal of Midwifery Women’s Health, Vol. 57, No. 1, 2012, pp. 82-85. doi:10.1111/j.1542-2011.2011.00105.x
[4] N. R. Gavva, J. J. Treanor, A. Garami, L. Fang, S. Surapaneni, A. Akrami, F. Alvarez, A. Bak, M. Darling, A. Gore, G. R. Jang, J. P. Kesslak, L. Ni, M. H. Norman, G. Palluconi, M. J. Rose, M. Salfi, E. Tan, A. A. Romanovsky, C. Banfield and G. Davar, “Pharmacological Blockade of the Vanilloid Receptor TRPV1 Elicits Marked Hyperthermia in Humans,” Pain, Vol. 136, No. 1-2, 2008, pp. 202-210. doi:10.1016/j.pain.2008.01.024
[5] A. G. Vinuesa, R. Sancho, C. García-Limones, A. Behrens, P. Dijke, M. A. Calzado and E. Mu?oz, “Vanilloid Receptor-1 Regulates Neurogenic Inflammation in Colon and Protects Mice from Colon Cancer,” Cancer Research, Vol. 72, No. 7, 2012, pp. 1705-1716
[6] N. R. Gavva, A. W. Bannon, S. Surapaneni, D. N. Hovland Jr., S. G. Lehto, A. Gore, T. Juan, H. Deng, B. Han, L. Klionsky, R. Z. Kuang, A. Le, R. Tamir, J. Wang, B. Youngblood, D. Zhu, M. H. Norman, E. Magal, J. J. S. Treanor and J.-C. Louis, “The Vanilloid Receptor TRPV1 Is Tonically Activated in Vivo and Involved in Body Temperature Regulation,” Journal of Neuroscience, Vol. 27, No. 13, 2007, pp. 3366-3374.
[7] A. Leffler, A. Lattrell, S. Kronewald, F. Niedermirtl and C. Nau, “Activation of TRPA1 by Membrane Permeable Local Anesthetics,” Molecular Pain, Vol. 7, 2011, p. 62.
[8] R. M. Sappington and D. J. Calkins, “Contribution of TRPV1 to Microglia-Derived IL-6 and NFkappaB Translocation with Elevated Hydrostatic Pressure,” Investigative Ophthalmology & Visual Science, Vol. 49, No. 7, 2008, pp. 3004-3017. doi:10.1167/iovs.07-1355
[9] S. Talbot, J. P. Dias1, K. Lahjouji, M. R Bogo, M. M. Campos, P. Gaudreau and R. Couture, “Activation of TRPV1 by Capsaicin Induces Functional Kinin B1 Receptor in Rat Spinal Cord Microglia,” Journal of Neuroinflammation, Vol. 9, 2012, p. 16.
[10] C. A. Reilly, M. E. Johansen, D. L. Lanza, J. Lee, J.-O. Lim and G. S. Yost, “Calcium-Dependent and Independent Mechanisms of Capsaicin Receptor (TRPV1)-Mediated Cytokine Production and Cell Death in Human Bronchial Epithelial Cells,” Journal of Biochemical and Molecular Toxicology, Vol. 19, No. 4, 2005, pp. 266-275.
[11] D. Purves, et al., “Neuroscience,” Sinauer Associates Inc., Sunderland, 2004.
[12] T. A. Barnett and D. S. Kapp, “Reduction of Pain and Local Complications When Buffered Lidocaine Solution Is Used as a Local Anesthetic in Conjunction with Hyperthermia Treatments: Results of a Randomized Trial,” International Journal of Radiation Oncology, Biology, Physics, Vol. 23, No. 3, 1992, pp. 585-591. doi:10.1016/0360-3016(92)90015-A
[13] L. E. Riley, A. C. Celi, A. B. Onderdonk, D. J. Roberts, L. C. Johnson, L. C. Tsen, L. Leffert, M. C. Pian-Smith, L. J. Heffner, S. T. Haas and E. S. Lieberman, “Association of Epidural-Related Fever and Noninfectious Inflammation in Term Labor,” Obstetrics & Gynecology, Vol. 117, No. 3, 2011, pp. 588-595. doi:10.1097/AOG.0b013e31820b0503
[14] M. J. Caterina, M. A. Schumacher, M. Tominaga, T. A. Rosen, J. D. Levine and D. Julius, “The Capsaicin Receptor: A Heat-Activated Ion Channel in the Pain Pathway,” Nature, Vol. 389, No. 6653, 1997, pp. 816-824. doi:10.1038/39807
[15] K. W. Ho, N. J Ward and D. J. Calkins, “Review Article TRPV1: A Stress Response Protein in the Central Nervous System,” American Journal of Neurodegenerative Disease, Vol. 1, No. 1, 2012, pp. 1-14.
[16] A. Leffler, M. J. Fischer, D. Rehner, S. Kienel, K. Kistner, S. K. Sauer, N. R. Gavva, P. W. Reeh and C. Nau1, “The Vanilloid Receptor TRPV1 Is Activated and Sensitized by Local Anesthetics in Rodent Sensory Neurons,” Journal of Clinical Investigation, Vol. 118, No. 2, 2008, pp. 763-776.
[17] A. M. Binshtok, P. Gerner, S. B. Oh, M. Puopolo, S. Suzuki, D. P. Roberson, T. Herbert, C. F. Wang, D. Kim, G. Chung, A. A. Mitani, G. K. Wang, B. P. Bean and C. J. Woolf, “Coapplication of Lidocaine and the Permanently Charged Sodium Channel Blocker QX-314 Produces a Long-Lasting Nociceptive Blockade in Rodents,” Anesthesiology, Vol. 111, No. 1, 2009, pp. 127-137.
[18] V. Di Marzo, K. Starowicz and L. Cristino, “TRPV1 Receptors in the Central Nervous System: Potential for Previously Unforeseen Therapeutic Applications,” Current Pharmaceutical Design, Vol. 14, No. 1, 2008, pp. 42-54. doi:10.2174/138161208783330790
[19] H. E. Gibson, J. G. Edwards, R. S. Page, M. J. Van Hook, J. A. Kauer, “TRPV1 Channels Mediate Long-Term Depression at Synapses on Hippocampal Interneurons,” Neuron, Vol. 57, No. 5, 2008, pp. 746-759. doi:10.1016/j.neuron.2007.12.027
[20] J. H. Peters, S. J. McDougall, J. A. Fawley, S. M. Smith, M. C. Andresen, “Primary Afferent Activation of Thermosensitive TRPV1 Triggers Asynchronous Glutamate Release at Central Neurons,” Neuron, Vol. 65, No. 5, 2010, pp. 657-669. doi:10.1016/j.neuron.2010.02.017
[21] Z. Wang, Y. Yang, H. Yang, J. E. Capó-Aponte, S. D. Tachado, J. M. Wolosin and P. S. Reinach, “NF-κB Feedback Control of JNK1 Activation Modulates TRPV1-Induced Increases in IL-6 and IL-8 Release by Human Corneal Epithelial Cells,” Molecular Vision, Vol. 17, 2011, pp. 3137-3146.

Copyright © 2023 by authors and Scientific Research Publishing Inc.

Creative Commons License

This work and the related PDF file are licensed under a Creative Commons Attribution 4.0 International License.