Aims: 

The preprotachykinin-A (TAC1) gene is expressed in the spinal dorsal horn, dorsal root ganglia and capsaicin-sensitive sensory neurons. The encoded peptides, substance-P (SP) and neurokinin-A (NKA), were shown to play a role in sensory, motor and vascular functions through the neurokinin 1 and 2 (NK1 and NK2) receptors, respectively. Therefore we studied the involvement of these tachykinins in traumatic mononeuropathy using gene-deficient (TAC1^-/-) mice.

Methods: 

Neuropathy was induced by tight ligation of 1/3 of the left sciatic nerve. The mechanonociceptive threshold of the paw was determined by dynamic plantar aesthesiometry and motor-coordination by Rota-Rod testing before and throughout 3 weeks after the procedure. Plantar microcirculation was measured with Laser Doppler imaging 4 weeks postoperatively. Vasodilation was induced by topical application of 5% mustard oil, which selectively stimulates the peptidergic sensory nerves.

Results: 

The mechanonociceptive thresholds of the two groups did not differ before the operation, but the motor-coordination of TAC1^-/- mice was significantly worse. Similar hyperalgesia (30%) developed in both groups1–3 weeks after nerve ligation. Motor functions were not affected by the operation, the originally observed difference between the groups was maintained. Chemical excitation of the sensory nerves with mustard oil induced similar vasodilation on the non-operated paws. In the area innervated by the damaged fibres a remarkable hyperemia occured in both groups, which could not be further increased by mustard oil stimulation.

Conclusion: 

Sciatic nerve ligation induces sensory neuropathy without any remarkable effect on the motor functions. SP and/or NKA are important mediators of the motor-coordination, but they play only a minor role in the development of hyperalgesia and neurogenic vasodilatation under peripherial neuropathic conditions.

Support: 

OTKA K73044, ETT 03-380/2009, SROP-4.2.1.B-10/2/KONV-2010-0002