Some of the reactions triggered by injury or section of an axon are shown in Figure1. Orthograde degeneration (Wallerian degeneration) occurs from the point of injury to the nerve terminal, interrupting neural transmission. Distal to the injury, the membrane breaks down and the myelin sheath degenerates. The proximal axon also is affected and may undergo retrograde degeneration and die. The cell body of the injured neuron swells, the nucleus moves to an eccentric position, and the rough endoplasmic reticulum gets fragmented (chromatolytic reaction).
Fig1. Changes occurring in a neuron when its axon is crushed or injured. The distal axon stump separates from the cell body, orthograde (Wallerian) degeneration occurs from the point of damage to the terminal, and the myelin sheath degenerates. The cell body of the injured neuron swells and the endoplasmic reticulum is fragmented as part of the chromatolytic reaction.
The nerve then starts to regrow, with multiple small branches projecting along the path the axon previously followed (regenerative sprouting). Axons sometimes grow back to their original targets, especially in locations like the neuro muscular junction. However, nerve regeneration is generally limited because axons often become entangled in the area of tissue damage at the site where they were disrupted. This difficulty has been reduced by administration of neurotrophins.
When the motor nerve to skeletal muscle is cut and allowed to degenerate, the muscle gradually becomes extremely sensitive to acetylcholine. This is called denervation hypersensitivity or supersensitivity. Normally nicotinic receptors are located only in the vicinity of the motor endplate where the axon of the motor nerve terminates. When the motor nerve is severed, there is a marked proliferation of nicotinic receptors over a wide region of the neuromuscular junction. Denervation supersensitivity also occurs at autonomic junctions. Smooth muscle, unlike skeletal muscle, does not atrophy when denervated, but it becomes hyperresponsive to the chemical mediator that normally activates it. This hyperresponsiveness can be demonstrated by using pharmacologic tools rather than actual nerve section. Prolonged use of a drug such as reserpine can be used to deplete transmitter stores and prevent the target organ from being exposed to norepinephrine for an extended period. Once the drug usage is stopped, smooth muscle and cardiac muscle will be supersensitive to subsequent release of the neurotransmitter.
Denervation hypersensitivity has multiple causes. As noted in Chapter 2, a deficiency of a given chemical messenger generally produces an up-regulation of its receptors. Another factor is a lack of reuptake of secreted neurotransmitters.
