MECHANICAL SENSITIVITY OF MUSCLE AFFERENTS IN A NERVE TREATED WITH COLCHICINE

The experiments reported here demonstrate that the mechanical sensitiv ity of peripheral nerve fibres typically seen after injury can be indu ced without overtly injuring the nerve, but by simply applying colchic ine topically to the nerve. In cats anaesthetised with pentobarbitone sodium, the medial gastrocnemius nerve was exposed and 10 mM colchicin e applied topically for 15 min. The animals recovered from the operati on normally and showed no subsequent motor deficit. Six days later ani mals were re-anaesthetised, a laminectomy carried out and responses re corded in single afferents at the level of the dorsal root. It was fou nd that many afferents, particularly those with conduction velocities in the group II-III range, had become sensitive to local mechanical st imulation of the nerve in the region treated with colchicine and showe d slowly adapting responses to stretch of the nerve. Many of the small er fibres exhibited spontaneous activity. Mechanically sensitive affer ents exhibited impulse conduction blocks at the colchicine-treated sit e. Some afferents, which appeared to conduct impulses normally through the treated region, were associated with muscle receptors having norm al response properties. However, other muscle receptors were clearly a bnormal and were insensitive to muscle stretch or contraction or exhib ited only phasic responses. When the nerve was cut proximal to the col chicine-treated site, some, but not all, spontaneous activity was abol ished. It was subsequently shown using a collision technique that the activity in some axons had its origin in the cell body in the dorsal r oot ganglion. In one experiment, it was shown that after nerve section proximal to the colchicine-treated region three of five axons switche d their activity from a peripheral to a central origin. It is postulat ed that colchicine disrupts fast axonal transport of mechanically sens itive or voltage-sensitive ion channels, from the cell body to the per ipheral terminals of the axons, leading to an accumulation of these ch annels at the treated site. This induces mechanical sensitivity and sp ontaneous activity. It is postulated that interruption of a retrograde ly transported signal induces the spontaneous activity in the cell bod y. These experiments suggest that an important influence is exerted by the cell body on the peripheral terminals of mechanoreceptors to conf er on them their normal response properties.