DOI: 10.1097/PRS.0b013e318289456f

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PMID: 23629081

Issn Print: 0032-1052

Publication Date: 2013/05/01


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Discussion: Patterns of Target Tissue Reinnervation and Trophic Factor Expression after Nerve Grafting

Paul S. Cederna

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Excerpt

Peripheral nerve injuries result in both motor and sensory deficits that lead to pronounced functional deficits. Although there are many techniques available for the management of peripheral nerve injuries, including primary end-to-end repair, autogenous nerve grafting, biological and synthetic peripheral nerve conduits, and bioactive alternative peripheral nerve conduits, recovery following any nerve injury is incomplete.1 Many factors contribute to the compromised functional recovery, including the time required to achieve end organ reinnervation, the quality of the nerves used for the repair, the effects of chronic denervation on Schwann cell phenotype, and the length of the nerve gap requiring repair.2 As basic and clinical scientists work to define new approaches to optimize functional recovery following peripheral nerve injury and repair, more rigorous outcome measures are required to determine the most critical elements of recovery: how well the end organs function following a nerve repair.
For many years, we have used histomorphometric analyses to define outcomes following various peripheral nerve manipulations, including end-to-end neurorrhaphy, end-to-side neurorrhaphy, interposition nerve grafting, and nerve gap repair using biological and synthetic nerve conduits. We have also used histomorphometric analysis to determine the impact of various growth factors and cellular therapies on neural regeneration. Nerve histomorphometry is a reliable and reproducible technique to quantitatively measure how well the motor and sensory axons sprout new branches and elongate distally.3,4 By measuring the quantity and quality of the axons (i.e., axon numbers, axon cross-sectional area, percentage neural tissue, and myelin thickness) distal to a nerve repair site, the investigator can predict the impact of various manipulations on neural regeneration and functional recovery distally. However, this is a relatively indirect approach for assessment of functional outcomes because it does not actually measure functional outcomes but uses anatomical measurements in the nerve as a proxy for peripheral nerve regeneration and functional reinnervation. Of course, if there are fewer axons distal to a nerve repair site in one experimental group compared with another, it is reasonable to predict that the group with the greater numbers of axons will have improved functional recovery. However, this is only an indirect measure and certainly not definitive.
A wealth of literature exists using muscle contractile properties following peripheral nerve injury and repair to define functional outcomes. By measuring twitch force, maximum tetanic isometric force, time to peak tension, and half relaxation time, the investigators can quantitatively assess how well the motor axons have established functional connections within the muscle following any proximal nerve intervention.5,6 These are critically important outcome measures because the purpose of any motor nerve repair is to reestablish motor function. In addition, maximum power production and sustained power can provide additional measurements of the effectiveness of muscle reinnervation by evaluating both force and velocity of muscle contraction.7–9 Single motor unit contractile properties can also be measured using complex experimental and surgical techniques to define the contractile properties of individual single motor units within the reinnervated muscle, including the physiologic properties of each motor unit (slow oxidative, fast oxidative glycolytic, and fast glycolytic).10–12 Considered together, this information can provide quantitative assessments of muscle reinnervation following any proximal nerve manipulation. These tools have been effectively used for many years and provide outstanding outcome measures.
Functional outcomes following nerve manipulations have also been extensively evaluated using walking track analyses, walking biomechanics with motion tracking, grooming tests, tapered beam walking, and ladder climbing.13,14 Each of these outcome measures provides information regarding the extent of reinnervation and also the quality of reinnervation. In fact, some of these outcomes assess not only the amount of muscle reinnervation but also the coordination of that function.
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