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Sural Hypersensitivity after Nerve Transection depends on Anatomical Differences in the Distal Tibial Nerve of Mice and Rats
Elisabeth Maria Brakkee, MD, MSc1; Erick DeVinney, BS2; Niels Eijkelkamp, PhD3; J Henk Coert, MD, PhD4
1UMC Utrecht, Utrecht, Netherlands; 2AxoGen, Alachua, FL; 3Universiteit Utrecht, Utrecht, Netherlands; 4Utrecht University Medical Center, Utrecht, Netherlands

Introduction: Mice and rats are often used for neuropathic pain models. The older models involve a proximal nerve lesion (above knee), e.g. Spared Nerve Injury and Chronic Constriction Injury model, and are described in both mice and rats. More recently developed models involve a transection or ligation of distal nerves (below knee), e.g. Distal Nerve Injury model, Tibial Neuroma Transposition model and Medial Plantar Nerve Ligation model. These models are described in either mice or rats. This study elaborates whether differences in anatomy of the distal tibial nerve in both mice and rats has implications for the development of sural nerve hypersensitivity after tibial nerve transection.
Methods: Anatomical measurements were performed under a surgical microscope on surplus mice and rats of other experiments without any surgical history of the hindlimbs (n=16 rat hindlimbs and n=16 mice hindlimbs). To differentiate between the lateral and medial plantar nerve (LPN and MPN), the nerves were followed by plantar dissection. In addition, surgery was performed on 48 rats and 16 mice; Sham (16 rats, 8 mice), MPN cut (16 rats, 8 mice) and tibial nerve cut (16 rats). In addition, the development of sural mechanical sensitivity after transection of the MPN or whole tibial nerve was assessed using von Frey test at baseline and once per week after surgery for 8 weeks.
Results: The bifurcation of the tibial nerve into the MPN and LPN is situated proximal to the ankle in all examined mice and rats. The sural nerve joins the LPN in mice, but not in rats. A proximal communicating branch is present between the LPN and MPN in rats, but not in mice. MPN transection caused significant hypersensitivity at the hind paw at the sural nerve distribution in mice compared to Sham, but not in rats. In rats, sural hypersensitivity only developed when both MPN and LPN were cut (figure 1).
Conclusions: Inter-species variation in nerve anatomy should be taken in consideration when performing surgery to induce plantar hypersensitivity in rodents, because mechanical hypersensitivity can be induced by selectively cutting the MPN in mice, but in rats both plantar branches need to be transected to induce sural hypersensitivity. This also partially explains why models involving a distal nerve lesion are described in either mice or rats.


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