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Papers of the Week

Papers: 16 Mar 2019 - 22 Mar 2019

Animal Studies

2019 Aug

Exp Neurol


Nociceptor-dependent locomotor dysfunction after clinically-modeled hindlimb muscle stretching in adult rats with spinal cord injury.


Keller AV, Hainline C, Rees K, Krupp S, Prince D, Wood BD, Shum-Siu A, Burke DA, Petruska JC, Magnuson DSK
Exp Neurol. 2019 Aug; 318:267-276.
PMID: 30880143.


In the course of investigating how common clinical treatments and adaptive technologies affect recovery after spinal cord injury (SCI), we discovered that a clinically-modeled hindlimb stretching protocol dramatically, but transiently, reduces locomotor function. Nociceptive sensory input is capable of altering motor output at the spinal level, and nociceptive neurons are sensitized after SCI. Here we tested the possibility that the stretch-induced motor deficits required the presence of nociceptors using neonatal capsaicin induced depletion of TRPV1+ nociceptive neurons. Following maturation, animals received 25 g-cm contusive SCI at T10. After plateau of locomotor recovery at 6 weeks, daily stretching was performed for 3 weeks, followed by 2 weeks without stretch, and again for two additional weeks. Animals were sacrificed 2 h after the last stretching session for histological assessments. The expected stretch-induced drops in locomotor function were observed in nociceptor-intact animals but were nearly absent in nociceptor-depleted animals. These functional changes were accompanied by corresponding increases in the number of c-Fos + nuclei throughout the lumbar enlargement. As expected, nociceptor-depleted animals had very little CGRP+ axonal innervation of the dorsal horn. However, in nociceptor-intact animals the expected post-SCI increase in CGRP+ innervation was significantly enhanced in animals that received stretching, implying additional stretch-induced intraspinal sprouting. These results indicate that locomotor dysfunction following hindlimb muscle stretch in animals with incomplete SCI involves C-fibers, adding a negative post-SCI role to their adaptive roles (e.g., bladder control), and suggesting that the clinical use of muscle stretching to combat contractures and spasticity may be unintentionally detrimental to locomotor function.