From the Guidelines
Yes, a transplanted area becomes denervated during the transplantation process, and it will typically reinervate over time. When tissue is transplanted, the nerves supplying that tissue are severed, resulting in complete loss of sensation and neural control in the transplanted area. This is evident in heart transplantation, where the denervated heart has altered physiology, affecting exercise tolerance, physical rehabilitation, and pharmacotherapeutic intervention 1. Reinervation occurs gradually as nerve fibers from the recipient site grow into the transplanted tissue.
The process of reinervation can be influenced by various factors, including the type of tissue transplanted, the distance nerves must regenerate, patient age, and surgical technique. For instance, in intestinal transplantation, the recovery of graft functions can be affected by nonimmunologic factors such as preservation injury, enteric lymphatic disruption, and central denervation 1. However, most patients achieve long-term gastrointestinal rehabilitation with full nutritional autonomy, indicating some level of reinervation and functional recovery.
The extent and quality of reinervation vary, but nerve regeneration occurs at a rate of approximately 1-3 mm per day. Sensory reinnervation usually precedes motor reinnervation, and patients may experience paresthesia (abnormal sensations) during the recovery process. Some transplanted areas may never regain complete normal sensation or function due to imperfect nerve regeneration patterns, but most patients experience significant improvement over time.
Key factors influencing the outcome of reinervation include:
- Type of tissue transplanted
- Distance nerves must regenerate
- Patient age
- Surgical technique
- Presence of nonimmunologic factors such as preservation injury and enteric lymphatic disruption
Physical therapy and rehabilitation are often important components of recovery to maximize functional outcomes as reinervation progresses. By understanding the process of denervation and reinervation, healthcare providers can better manage patient expectations and develop targeted rehabilitation strategies to improve quality of life and functional outcomes in transplant recipients.
From the Research
Nerve Regeneration in Transplanted Organs
- Transplanted organs are initially denervated, but they can reinervate over time 2
- The process of nerve regeneration in transplanted organs is complex and not fully understood, involving the sympathetic, parasympathetic, and visceral sensory plexuses 2
Reinnervation of Denervated Muscles
- Reinnervation of denervated muscles can be achieved through embryonic motoneuron transplantation into peripheral nerves undergoing Wallerian degeneration 3
- The optimal time for transplantation of motoneurons into the peripheral nerve is 1 week after nerve transection, but neurons transplanted 24 weeks after denervation can still survive and regenerate axons 3
- Side-to-side nerve grafts can sustain chronically denervated peripheral nerve pathways during axon regeneration and result in improved functional reinnervation 4
Delaying Denervated Muscle Atrophy
- Transplanting fetal neural stem cells into peripheral nerve can delay muscle atrophy by differentiating into neurons and forming functional neuromuscular junctions with denervated muscle 5
- Matrix metalloproteinase 3 deletion can preserve denervated motor endplates after traumatic nerve injury by preventing the degradation of agrin 6
Mechanisms of Reinnervation
- The mechanisms of reinnervation in transplanted organs and denervated muscles are complex and involve multiple factors, including the sympathetic, parasympathetic, and visceral sensory plexuses, as well as the degradation of agrin and other molecules 2, 3, 4, 5, 6
- Further research is needed to fully understand the mechanisms of reinnervation and to develop effective therapies for promoting nerve regeneration and preventing muscle atrophy 2, 3, 4, 5, 6