Properties of peripherally induced persistent hindlimb flexion in rat: involvement of N-methyl-D-aspartate receptors and capsaicin-sensitive afferents.

In the sodium pentobarbital anesthetized rat, percutaneous electrical stimulation (2 mA, 7 ms, 100 Hz, 60 min) across the upper hindlimb produces an ipsilateral hindlimb flexion that persists following spinal transection. Using this preparation, the following were found. (1) Flexion was observed in both the intact and acutely spinalized (T7) rat 10 hours to two weeks following induction, but was negligible at six weeks. (2) Pretreatment of intact rats with the non-competitive N-methyl-D-aspartate (NMDA) receptor antagonists, ketamine HCl and MK-801, reduced persistent hindlimb flexion in a dose-dependent manner. (3) Pretreatment of spinalized rats with MK-801 reduced the amount of flexion, observed at 30 min following stimulation. However at 72 hrs following stimulation, administration of MK-801 to acutely spinalized rats had no effect on flexion. (4) Capsaicin pretreatment, of either neonates or adults, reduced the amount of flexion observed at 30 min following stimulation, but only adult capsaicin pretreatment reduced flexion at 72 h. (5) At 72 h following induction, bilateral dorsal rhizotomy (T11-L6) of acutely spinalized rats had no significant effect on flexion when compared to pre-rhizotomy levels. However, the subsequent removal of the hindlimb skin produced a significant reduction in flexion, and the remaining flexion was eliminated by the removal of the thoracolumbar spinal cord and cauda equina. These combined results suggest that prolonged activation of C-afferents and NMDA receptors induce a persistent hindlimb flexion in rat that is maintained at the level of the spinal cord.