Sural hypersensitivity after nerve transection depends on anatomical differences in the distal tibial nerve of mice and rats.

INTRODUCTION: Various mouse and rat models of neuropathic pain after nerve injury exist. Whilst some models involve a proximal nerve lesion or ligation of the sciatic trifurcation in mice and rats, others consists of a transection or ligation of distal nerves at the tibial bifurcation in mice or rats. The level of nerve cut directly affects the magnitude of hypersensitivity, and anatomical differences between mice and rats might therefore impact the development of hypersensitivity after distal tibial nerve transection as well. METHODS: The bifurcation of the distal tibial nerve into the medial and lateral plantar nerve (MPN and LPN), and the presence of anatomical differences in sural and tibial nerve distribution between mice and rat was evaluated. Sural mechanical sensitivity after transection of the MPN or whole tibial nerve was assessed using von Frey test until 8 weeks after surgery in 48 rats and 16 mice. RESULTS: The bifurcation of the tibial nerve into the MPN and LPN is situated proximal to the ankle in both 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 in mice caused hypersensitivity of the hindpaw innervated by the sural nerve, but not in rats. In rats, sural hypersensitivity only developed when both MPN and LPN were cut. CONCLUSION: Inter-species variation in nerve anatomy should be taken in consideration when performing surgery to induce plantar hypersensitivity in rodents.

Mirror-image pain after nerve reconstruction in rats is related to enhanced density of epidermal peptidergic nerve fibers.

Mirror-image pain is a phenomenon in which unprovoked pain is detected on the uninjured contralateral side after unilateral nerve injury. Although it has been implicated that enhanced production of nerve growth factor (NGF) in the contralateral dorsal root ganglion is important in the development of mirror-image pain, it is not known if this is related to enhanced expression of nociceptive fibers in the contralateral skin. Mechanical and thermal sensitivity in the contralateral hind paw was measured at four different time points (5, 10, 20 and 30weeks) after transection and immediate end-to-end reconstruction of the sciatic nerve in rats. These findings were compared to the density of epidermal (peptidergic and non-peptidergic) nerve fibers on the contralateral hind paw. Mechanical hypersensitivity of the contralateral hind paw was observed at 10weeks PO, a time point in which both subgroups of epidermal nerve fibers reached control values. Thermal hypersensitivity was observed with simultaneous increase in the density of epidermal peptidergic nerve fibers of the contralateral hind paw at 20weeks PO. Both thermal sensitivity and the density of epidermal nerve fibers returned to control values 30weeks PO. We conclude that changes in skin innervation and sensitivity are present on the uninjured corresponding side in a transient pain model. Therefore, the contralateral side cannot serve as control. Moreover, the current study confirms the involvement of the peripheral nervous system in the development of mirror-image pain.