Cellular components necessary for mechanoelectrical transduction are conveyed to primary afferent terminals by fast axonal transport

Axonal transport of neurotransmitter receptors is a well established phenomenon. In this study, we sought to determine whether the cellular components necessary for mechanical-to-electrical transduction in primary afferents are also conveyed to the peripheral terminals via fast axonal transport. In previous studies, severed cutaneous nerves have been shown to develop mechanical sensitivity at their ligated ends within hours of injury. Since the rate of development of this mechanical sensitivity was temperature dependent, we postulated that axonal transport was involved. In this study, we performed two experiments in which the rate of axonal transport was modified. In the first experiment, the nerve was cut at a proximal site to block the supply of additional transported components to the distal end of the nerve. At a point 80 to 120 mm distal to this proximal cut, a nerve crush and ligation were performed either 3 or 12 h after the proximal nerve ligation. The centripetally conducted action potentials generated by applying mechanical stimuli to the nerve subjacent to the distal ligature were recorded 10 h after the distal ligature was placed. Given a fast axonal transport rate of 400 mm/day, transported molecules should traverse a 100-mm segment within 6 h. Consistent with this calculation, 29% of the myelinated fibers responded to mechanical stimuli when the time lapse between lesions was 3 h, whereas only 3% responded when the time between lesions was 12 h. In the second experiment, axonal transport was enhanced by a prior nerve injury (conditioning lesion). Seven days after this lesion, the nerve was reinjured proximal to the conditioning lesion location, and the development of mechanosensitivity at the acute injury site was assessed. The rate of development of mechanical sensitivity was greatly enhanced by the conditioning lesion, and 44% of the myelinated fibers responded to mechanical stimuli 10 h after the acute injury. These two studies support the ideas that: (1) the cellular components necessary for mechanical-to-electrical transduction are transported to distal sensory terminals via fast axonal transport; (2) nerve crush and ligation lead to ectopic expression of these transducers at the nerve injury site; and (3) prior nerve injury increases the rate of development of mechanosensitivity, perhaps by increasing the production of transducers.