Retrograde labeling correlates with motor unit number estimation in rapid-stretch nerve injury

Muscle Nerve. 2023 Feb;67(2):169-176. doi: 10.1002/mus.27756. Epub 2022 Dec 8.

Abstract

Introduction/aims: Rapid-stretch nerve injuries represent a substantial treatment challenge. No study has examined motor neuron connection after rapid-stretch injury. Our objective in this study was to characterize the electrophysiological properties of graded rapid-stretch nerve injury and assess motor neuron health using retrograde labeling and muscle adenosine triphosphatase (ATPase) histology.

Methods: Male C57BL/6 mice (n = 6 per group) were rapid-stretch injured at four levels of severity: sham injury, stretch within elastic modulus, inelastic deformation, and stretch rupture. Serial compound muscle action potential (CMAP) and motor unit number estimation (MUNE) measurements were made for 48 days, followed by retrograde labeling and muscle ATPase histology.

Results: Elastic injuries showed no durable abnormalities. Inelastic injury demonstrated profound initial reduction in CMAP and MUNE (P < .036) on day 2, with partial recovery by day 14 after injury (CMAP: 40% baseline, P = .003; MUNE: 55% baseline, P = .033). However, at the experimental endpoint, CMAP had recovered to baseline with only limited improvement in MUNE. Inelastic injury led to reduced retrograde-labeled neurons and grouped fiber type histology. Rupture injury had severe and nonrecovering electrophysiological impairment, dramatically reducing labeled neurons (P = .005), and atrophic or type 1 muscle fibers. There was an excellent correlation between MUNE and retrograde-labeled tibial motor neurons across injury severities (R2 = 0.96).

Discussion: There was no significant electrophysiological derangement in low-severity injuries but there was recoverable conduction block in inelastic injury with slow recovery, potentially due to collateral sprouting. Rupture injuries yielded permanent failure of injured axons to reinnervate. These results provide insight into the pathophysiology of clinical injuries and recovery.

Keywords: motor neuron; motor unit number estimation; neuroma; neuroma-in-continuity; peripheral nerve; stretch injury.

MeSH terms

  • Action Potentials / physiology
  • Adenosine Triphosphatases / analysis
  • Animals
  • Elastic Modulus
  • Male
  • Mice
  • Mice, Inbred C57BL
  • Motor Neurons / pathology
  • Muscle, Skeletal / enzymology
  • Muscle, Skeletal / innervation
  • Muscle, Skeletal / pathology
  • Peripheral Nerve Injuries* / physiopathology
  • Rupture* / physiopathology

Substances

  • Adenosine Triphosphatases