Temporal and Qualitative Differences in the Development of Allodynic Behaviors between Mice and Rats in a Peripheral Nerve Injury Model


The spared nerve injury (SNI) model of neuropathic pain was first developed by Decosterd and Woolf in 2000 in Sprague Dawley rats to enhance reproducibility of injury and behavioral responses resulting from a partial nerve injury. Given the differences in methodology and inconsistent behavioral data published in the SNI model of neuropathic pain in mice, and given that interspecies behavioral comparisons using the same peripheral nerve injury are presently lacking, in this study we assessed the development of mechanical and cold allodynia for five weeks in C57BL/6 mice and Sprague Dawley rats that underwent SNI. In rats and mice, the tibial and peroneal branches were ligated then severed, leaving the sural branch intact. By controlling several factors in the surgical procedure and behavioral tests, we found that rats developed and maintained strong mechanical and robust cold allodynia immediately following the injury that was maintained for the duration of the experiment (five weeks). In comparison, mice developed mechanical allodynia to a lesser magnitude which peaked at 2 weeks, but did not develop cold allodynia. We found both temporal and qualitative differences in the development of allodynic behaviors between SNI-mice and SNI-rats. Parallel analysis of interspecies differences can be exploited to reveal novel molecular players leading to divergent pain behaviors.

Share and Cite:

Sideris, A. , Norcini, M. , Blanck, T. and Pinto, E. (2014) Temporal and Qualitative Differences in the Development of Allodynic Behaviors between Mice and Rats in a Peripheral Nerve Injury Model. Pain Studies and Treatment, 2, 121-127. doi: 10.4236/pst.2014.24019.

Conflicts of Interest

The authors declare no conflicts of interest.


[1] Macrae, W.A. (2001) Chronic Pain after Surgery. British Journal of Anaesthesia, 87, 88-98. http://dx.doi.org/10.1093/bja/87.1.88
[2] Johansen, A., et al. (2012) Persistent Postsurgical Pain in a General Population: Prevalence and Predictors in the Tromso Study. Pain, 153, 1390-1396. http://dx.doi.org/10.1016/j.pain.2012.02.018
[3] Decosterd, I. and Woolf, C.J. (2000) Spared Nerve Injury: An Animal Model of Persistent Peripheral Neuropathic Pain. Pain, 87, 149-158. http://dx.doi.org/10.1016/S0304-3959(00)00276-1
[4] Yang, F., et al. (2013) Analgesic Treatment with Pregabalin Does Not Prevent Persistent Pain after Peripheral Nerve Injury in the Rat. Pain, 155, 356-366.
[5] Wang, J., et al. (2011) A Single Subanesthetic Dose of Ketamine Relieves Depression-Like Behaviors Induced by Neuropathic Pain in Rats. Anesthesiology, 115, 812-821. http://dx.doi.org/10.1097/ALN.0b013e31822f16ae
[6] Swartjes, M., et al. (2011) Nonselective and NR2B-Selective N-Methyl-D-Aspartic Acid Receptor Antagonists Produce Antinociception and Long-Term Relief of Allodynia in Acute and Neuropathic Pain. Anesthesiology, 115, 165- 174. http://dx.doi.org/10.1097/ALN.0b013e31821bdb9b
[7] Shields, S.D., Eckert III, W.A and Basbaum, A.I. (2003) Spared Nerve Injury Model of Neuropathic Pain in the Mouse: A Behavioral and Anatomic Analysis. The Journal of Pain, 4, 465-470. http://dx.doi.org/10.1067/S1526-5900(03)00781-8
[8] Bourquin, A.F., et al. (2006) Assessment and Analysis of Mechanical Allodynia-Like Behavior Induced by Spared Nerve Injury (SNI) in the Mouse. Pain, 122, 14e1-14.
[9] Abe, K., Fujii, Y. and Nojima, H. (2011) Evaluation of Hyperalgesia in Spared Nerve Injury Model Using Mechanical, Thermal, and Chemical Stimuli in the Mouse. Neurological Research, 33, 656-662. http://dx.doi.org/10.1179/1743132810Y.0000000019
[10] Choi, Y., et al. (1994) Behavioral Signs of Ongoing Pain and Cold Allodynia in a Rat Model of Neuropathic Pain. Pain, 59, 369-376. http://dx.doi.org/10.1016/0304-3959(94)90023-X
[11] Hau, J. (2008) Animal Models for Human Diseases. In: Conn, P.M., Ed., Sourcebook of Models for Biomedical Research, Humana Press, New York, 3-8. http://dx.doi.org/10.1007/978-1-59745-285-4_1
[12] Richner, M., Bjerrum, O.J., Nykjaer, A. and Vaegter, C.B. (2011) The Spared Nerve Injury (SNI) Model of Induced Mechanical Allodynia in Mice. Journal of Visualized Experiments, 54, e3092.
[13] Smith, A.K., O’Hara, C.L. and Stucky, C.L. (2013) Mechanical Sensitization of Cutaneous Sensory Fibers in the Spared Nerve Injury Mouse Model. Molecular Pain, 9, 61. http://dx.doi.org/10.1186/1744-8069-9-61
[14] Kuhlein, H.N., Tegeder, I., M?ser, C., Lim, H.-Y., et al. (2011) Nerve Injury Evoked Loss of Latexin Expression in Spinal Cord Neurons Contributes to the Development of Neuropathic Pain. PLoS ONE, 6, e19270. http://dx.doi.org/10.1371/journal.pone.0019270
[15] Vachon, P., Millecamps, M., Low, L., Thompsosn, S.J., Pailleux, F., et al. (2013) Alleviation of Chronic Neuropathic Pain by Environmental Enrichment in Mice Well after the Establishment of Chronic Pain. Behavioral and Brain Functions, 9, 22. http://dx.doi.org/10.1186/1744-9081-9-22
[16] Solway, B., Bose, S.C., Corder, G., Donahue, R.R. and Taylor, B.K. (2011) Tonic Inhibition of Chronic Pain by Neuropeptide Y. Proceedings of the National Academy of Sciences of the United States of America, 108, 7224-7229. http://dx.doi.org/10.1073/pnas.1017719108
[17] Pertin, M., Gosselin, R.D. and Decosterd, I. (2012) The Spared Nerve Injury Model of Neuropathic Pain. Methods in Molecular Biology, 851, 205-212. http://dx.doi.org/10.1007/978-1-61779-561-9_15
[18] Sideris, A.N.M., Russo, L., Chen, J., Mason, S., Blanck, T.J.J. and Recio-Pinto, E. (2013) Knock out of the Cannabinoid 1 Receptor Promotes Recovery from Mechanical but Not from Cold Allodynia Following Sural Spared Nerve Injury in Mice. Neuropathic Pain Special Interest Group Congress, Toronto.
[19] Kim, K.J., Yoon, Y.W. and Chung, J.M. (1997) Comparison of Three Rodent Neuropathic Pain Models. Experimental Brain Research, 113, 200-206. http://dx.doi.org/10.1007/BF02450318
[20] Persson, A.-K., Xu, X.-J., Wiesenfeld-Hallin, Z., Devor, M. and Fried, K. (2010) Expression of DRG Candidate Pain Molecules after Nerve Injury—A Comparative Study among Five Inbred Mouse Strains with Contrasting Pain Phenotypes. Journal of the Peripheral Nervous System, 15, 26-39. http://dx.doi.org/10.1111/j.1529-8027.2010.00249.x
[21] Xu, X.-J., Plesan, A., Yu, W., Hao, J.-X. and Wiesenfeld-Hallin, Z. (2001) Possible Impact of Genetic Differences on the Development of Neuropathic Pain-Like Behaviors after Unilateral Sciatic Nerve Ischemic Injury in Rats. Pain, 89, 135-145. http://dx.doi.org/10.1016/S0304-3959(00)00356-0
[22] Gierthmuhlen, J., Maier, C., Baron, R., T?lle, T., Treede, R.-D., et al. (2012) Sensory Signs in Complex Regional Pain Syndrome and Peripheral Nerve Injury. Pain, 153, 765-774. http://dx.doi.org/10.1016/j.pain.2011.11.009
[23] Zhao, C.S., Chen, L., Tao, Y.-X., Tall, J.M., et al. (2007) Lumbar Sympathectomy Attenuates Cold Allodynia but Not Mechanical Allodynia and Hyperalgesia in Rats with Spared Nerve Injury. The Journal of Pain, 8, 931-937. http://dx.doi.org/10.1016/j.jpain.2007.06.008
[24] Young, E.E., Lariviere, W.R. and Belfer, I. (2012) Genetic Basis of Pain Variability: Recent Advances. Journal of Medical Genetics, 49, 1-9. http://dx.doi.org/10.1136/jmedgenet-2011-100386
[25] Kim, H., Clark, D. and Dionne, R.A. (2009) Genetic Contributions to Clinical Pain and Analgesia: Avoiding Pitfalls in Genetic Research. The Journal of Pain, 10, 663-693. http://dx.doi.org/10.1016/j.jpain.2009.04.001

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.