Comparative outcome measures in peripheral regeneration studies

Traumatic peripheral nerve injuries are common and often result in partial or permanent paralysis, numbness of the affected limb, and debilitating neuropathic pain. Experimental animal models of nerve injury have utilized a diversity of outcome measures to examine functional recovery following injury. Four primary categories of outcome measures of regenerative success including retrograde labeling with counts of regenerating neurons, immunohistochemistry and histomorphometry, reinnervation of target muscles, and behavioral analysis of recovery will be reviewed. Validity of different outcome measures are discussed in context of hindlimb, forelimb, and facial nerve injury models. Severity of nerve injury will be highlighted, and comparisons between nerve crush injury and more severe transection and neuroma-in-continuity nerve injury paradigms will be evaluated. The case is made that specific outcome measures may be more sensitive to assessing functional recovery following nerve injury than others. This will be discussed in the context of the lack of association between certain outcome measures of nerve regeneration. Examples of inaccurate conclusions from specific outcome measures will also be considered. Overall, researchers must therefore take care to select appropriate outcome measures for animal nerve injury studies dependant on the specific experimental interventions and scientific questions addressed.