Addition of Capsaicin to Local Anesthetics for Spinal Anesthesia in Rats Shortens Motor Deficits and Prolongs Anti-Nociception

DOI: 10.4236/ojanes.2014.46019   PDF   HTML   XML   2,500 Downloads   3,426 Views  


Background and Objectives: Sensory-selective anesthesia, greater or longer-lasting anti-nociception than motor or autonomic deficits, is often clinically desirable but traditional local anesthetics rarely have such selective actions. Addition of capsaicin to tertiary amine local anesthetics has recently been reported to affect a preferential prolongation of nociceptive over motor block in rat sciatic nerve. We hypothesized that this combination when used intrathecally will also prolong nociceptive block. Methods: Under sevoflurane inhalation anesthesia, rats were injected intrathecally either with local anesthetics (bupivacaine, lidocaine, and articaine) alone or simultaneously with capsaicin. Motor block was evaluated by the contractile function of foot muscles, from proximal to distal. Anti-nociception was assessed by reductions in nocifensive withdrawal and vocalization induced by pinching the skin fold over the lateral metatarsus. Durations and degrees of deficits were assessed, along with complete recovery times and compared between local anesthetics alone and in combination with capsaicin. Results: Addition of capsaicin to any of the local anesthetics shortened motor deficits. Bupivacaine, lidocaine and articaine motor blocks were reduced upon combination with capsaicin to 0.32, 0.32 ans 0.43 of the duration from the respective local anesthetic alone. Duration of anti-nociceptive action was increased by capsaicin only for articaine. The ratios of block nociceptive to sensory block durations were 3.5, 5.1 and 3.3 for the respective local anesthetics. Conclusions: Intrathecal injection of capsaicin combined with local anesthetics produced a preferentially longer anti-nociceptive deficit. These combinations have potential clinical applications, including peri-operative spinal anesthesia and pain management.

Share and Cite:

Wang, C. , Wang, J. , Soens, M. , Gerner, P. and Strichartz, G. (2014) Addition of Capsaicin to Local Anesthetics for Spinal Anesthesia in Rats Shortens Motor Deficits and Prolongs Anti-Nociception. Open Journal of Anesthesiology, 4, 123-130. doi: 10.4236/ojanes.2014.46019.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Raymond, A.S. and Gissen A.J. (1987) Mechanisms of Differential Nerve Block. In Strichartz, G.R., Ed., Local Anesthetics, Springer-Verlag, Heidelberg, New York, 95-164.
[2] Fernandes, E.S., Fernandes, M.A. and Keeble, J.E. (2012) The Functions of TRPA1 and TRPV1: Moving away from Sensory Nerves. British Journal of Pharmacology, 166, 510-521.
[3] Chen, Y., Willcockson, H.H. and Valtschanoff, J.G. (2009) Influence of the Vanilloid Receptor TRPV1 on the Activation of Spinal Glia in Mouse Models of Pain. Experimental Neurology, 220, 383-390.
[4] Binshtok, A.M., Bean, B.P. and Woolf, C.J. (2007) Inhibition of Nociceptors by TRPV1-Mediated Entry of Impermeant Sodium Channel Blockers. Nature, 449, 607-610.
[5] Gerner, P., Binshtok, A.M., Wang, C.F., Hevelone, N.D., Bean, B.P., Woolf, C.J. and Wang, G.K. (2008) Capsaicin Combined with Local Anesthetics Preferentially Prolongs Sensory/Nociceptive Block in Rat Sciatic Nerve. Anesthesiology, 109, 872-878.
[6] Shen J., Fox, L.E. and Cheng, J. (2012) Differential Effects of Peripheral versus Central Coadministration of QX-314 and Capsaicin on Neuropathic Pain in Rats. Anesthesiology, 117, 365-380.
[7] Colvin, A.C., Wang, C.F., Soens, M.A., Mitani, A.A., Strichartz, G.R. and Gerner, P. (2011) Prolonged Cutaneous Analgesia with Transdermal Application of Amitriptyline and Capsaicin. Regional Anesthesia & Pain Medicine, 36, 236-240.
[8] Gokin, A. and Strichartz, G.R. (1999) Local Anesthetics Acting on the spinal cord. Access, Distribution, Pharmacology and Toxicology. In: Yaksh, T.L., Ed., Spinal Drug Delivery: Anatomy, Kinetics and Toxicology, Elsevier Publishers, New York, 477-501.
[9] Strichartz, G.R., Pastijn, E. and Sugimoto, K. (2009) Neural Physiology and Local Anesthetic Action. In: Cousins M.J., Carr D.B., Horlocker T.T., Bridenbaugh P.O., Eds., Neural Blockade in Clinical Anesthesia and Pain Medicine, Walters Kluwer-Lippincott Williams and Wilkins, Philadelphia, 26-47.
[10] Thalhammer, J.G., Vladimirova, M., Bershadsky, B. and Strichartz, G.R. (1995) Neurologic Evaluation of the Rat during Sciatic Nerve Block with Lidocaine. Anesthesiology, 82, 1013-1025.
[11] Mestre, C., Pelissier, T., Fialip, J., Wilcox, G. and Eschalier, A. (1994) A Method to Perform Direct Transcutaneous Intrathecal Injection in Rats. Journal of Pharmacological and Toxicological Methods, 32, 197-200.
[12] Frazier, D.T., Narahashi, T. and Yamada, M. (1970) The Site of Action and Active form of Local Anesthetics. II. Experiments with Quaternary Compounds. The Journal of Pharmacology and Experiment Therapeutics, 171, 45-51.
[13] Strichartz, G.R. (1973) The Inhibition of Sodium Currents in Myelinated Nerve by Quaternary Derivatives of Lidocaine. The Journal of General Physiology, 62, 37-57.
[14] Hille, B. (1977) Local Anesthetics: Hydrophilic and Hydrophobic Pathways for the Drug-Receptor Reaction. The Journal of General Physiology, 69, 497-515.
[15] Strichartz, G.R., Sanchez, V., Arthur, G.R., Chaftez, R. and Martin, D. (1990) Fundamental Properties of Local Anesthetics. II. Measured Octanol: Buffer Partition Coefficients and pKa Values of Clinically-Used Drugs. Anesthesia & Analgesia, 71, 158-170.
[16] Hille, B. (1977) The pH-Dependent Rate of Action of Local Anesthetics on the Node of Ranvier. Journal of General Physiology, 69, 475-496.
[17] Huang, J.H., Thalhammer, J.G., Raymond, S.A. and Strichartz, G.R. (1997) Susceptibility to Lidocaine of Impulses in Different Somatosensory Afferent Fibers of Rat Sciatic Nerve. Journal of Pharmacology and Experimental Therapeutics, 282, 802-811.
[18] Gokin, A.P., Philip, B. and Strichartz, G.R. (2001) Preferential Block of Small Myelinated Sensory and Motor Fibers by Lidocaine: In Vivo Electrophysiology in the Rat Sciatic Nerve. Anesthesiology, 95, 1441-1454.
[19] Leffler, A., Fischer, M.J., Rehner, D, Kienel, S., Kistner, K., Sauer, S.K., Gawa, N.R., Reeh, P.W. and Nau, C. (2008) The Vanilloid Receptor TRPV1 Is Activated and Sensitized by Local Anesthetics in Rodent Sensory Neurons. Journal of Clinical Investigation, 118,763-776.
[20] Roberson, D., Binshtok, A.M., Blasl, F., Bean, B.P. and Woolf, C.J. (2011) Targeting of Sodium Channel Blockers into Nociceptors to Produce Long-Duration Analgesia: A Systematic Study and Review. British Journal of Pharmacology, 164, 48-58.
[21] Sagie, I. and Kohane, D.S. (2010) Prolonged Sensory-Selective Nerve Blockade. Proceedings of the National Academy of Sciences of the United States of America, 107, 3740-3745.
[22] Nijs, J., Daenen, L., Cras, P., Struyf, F., Roussel, N. and Oostendorp, R.A.B. (2012) Nociception Affects Motor Output: A Review on Sensory-Motor Interaction with Focus on Clinical Implications. Clinical Journal of Pain, 28, 175-181.
[23] Yamamoto, S., Ohsawa, M. and Ono, H. (2013) Contribution of TRPV1 Receptor-Expressing Fibers to Spinal Ventral Root After-Discharges and Mechanical Hyperalgesia in a Spared Nerve Injury (SNI) Rat Model. Journal of Pharmacological Sciences, 121, 9-16.
[24] Vanegas, H. and Schaible, H.G. (2004) Descending Control of Persistent Pain: Inhibitory or Facilitatory? Brain Research Reviews, 46, 295-309.
[25] Liu, B.G., Zhuang, X.L., Li, S.T., Xu, G.H., Brull, S.J. and Zhang, J.M. (2001) Effects of Bupivacaine and Ropivacaine on High-Voltage-Activated Calcium Currents in the Dorsal Horn Neurons in Newborn Rats. Anesthesiology, 95, 139-143.
[26] Xiong, Z. and Strichartz, G.R. (1998) Inhibition by Local Anesthetics of Ca2+ Channels in Rat Anterior Pituitary Cells. European Journal of Pharmacology, 363, 81-90.
[27] Alberola-Die, A., Martinez-Pinna, J., González-Ros, J.M., Ivorra, I. and Morales, A. (2011) Multiple Inhibitory Actions of Lidocaine on Torpedo Nicotinic Acetylene Receptors Transplanted to Xenopus Oocytes. Journal of Neurochemistry, 117, 1009-1019.
[28] Sugimoto, M., Uchida, I. and Mashimo, T. (2003) Local Anesthetics Have Different Mechanisms and Sites of Action at the Recombinant N-methyl-D-aspartate (NMDA) Receptors. British Journal of Pharmacology, 138, 876-882.
[29] Hollmann, M.W., McIntire, W.E., Garrison, J.C. and Durieux, M.E. (2002) Inhibition of Mammalian Gq Protein Function by Local Anesthetics. Anesthesiology, 97, 1451-1457.
[30] Li, Y.M., Wingrove, D.E., Too, M.P., Marnerakis, M., Stimson, E.R., Strichartz, G.R. and Maggio, J.E. (1995) Local Anesthetics Inhibit Substance P Binding and Evoked Increases in Intracellular Ca+2. Anesthesiology, 82, 166-173.
[31] Regehr, W. and Stevens, C.F. (2001) Physiology of Synaptic Transmission and Short-Term Plasticity in Synapses. In: Cowan, W.M., Sudhof, T.C., Stevens, C.F., Eds., Synapses, Johns Hopkins Press, Baltimore, 155-156.
[32] Jin, D.Z., Guo, M.L., Xue, B., Fibuch, E.E., Choe, E.S., Mao, L.M. and Wang, J.Q. (2013) Phosphorylation and Feedback Regulation of Metabotropic Glutamate Receptor 1 by Calcium/Calmodulin-Dependent Protein Kinase II. Journal of Neuroscience, 33, 3402-3412.
[33] Gould, C.M. and Newton, A.C. (2008) The Life and Death of Protein Kinase C. Current Drug Targets, 9, 614-625.
[34] Mikawa, K., Maekawa, N., Hoshina, H., Tanaka, O., Shirakawa, J., Goto, R., Obara, H. and Kusunoki, M. (1990) Inhibitory Effect of Barbiturates and Local Anaesthetics on Protein Kinase C Activation. Journal of International Medical Research, 18, 153-160.

comments powered by Disqus

Copyright © 2020 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.