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Experimental muscle hyperalgesia modulates sensorimotor cortical excitability, which is partially altered by unaccustomed exercise

De Martino, Enricoa; Zandalasini, Matteoa; Schabrun, Siobhanb; Petrini, Lauraa; Graven-Nielsen, Thomasa,*

doi: 10.1097/j.pain.0000000000001351
Research Paper

Impaired corticomotor function is reported in patients with lateral epicondylalgia, but the causal link to pain or musculotendinous overloading is unclear. In this study, sensorimotor cortical changes were investigated using a model of persistent pain combined with an overloading condition. In 24 healthy subjects, the effect of nerve growth factor (NGF)-induced pain, combined with delayed-onset muscle soreness (DOMS), was examined on pain perception, pressure pain sensitivity, maximal force, and sensorimotor cortical excitability. Two groups (NGF alone and NGF + DOMS) received injections of NGF into the extensor carpi radialis brevis (ECRB) muscle at day 0, day 2, and day 4. At day 4, the NGF + DOMS group undertook wrist eccentric exercise to induce DOMS in the ECRB muscle. Muscle soreness scores, pressure pain thresholds over the ECRB muscle, maximal grip force, transcranial magnetic stimulation mapping of the cortical ECRB muscle representation, and somatosensory-evoked potentials from radial nerve stimulation were recorded at day 0, day 4, and day 6. Compared with day 0, day 4 showed in both groups: (1) increased muscle soreness (P < 0.01); (2) reduced pressure pain thresholds (P < 0.01); (3) increased motor map volume (P < 0.01); and (4) decreased frontal N30 somatosensory-evoked potential. At day 6, compared with day 4, only the DOMS + NGF group showed: (1) increased muscle soreness score (P < 0.01); (2) decreased grip force (P < 0.01); and (3) decreased motor map volume (P < 0.05). The NGF group did not show any difference on the remaining outcomes from day 4 to day 6. These data suggest that sustained muscle pain modulates sensorimotor cortical excitability and that exercise-induced DOMS alters pain-related corticomotor adaptation.

This article provides insight into the nature and temporal profile of sensorimotor cortical adaptation during sustained muscle soreness, relevant for understanding neuroplasticity during sustained pain.

aDepartment of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), SMI, Faculty of Medicine, Aalborg University, Aalborg, Denmark

bBrain Rehabilitation and Neuroplasticity Unit (BRAiN-u), School of Science and Heath, Western Sydney University, Sydney, Australia

Corresponding author. Address: Department of Health Science and Technology, Center for Neuroplasticity and Pain (CNAP), SMI, Faculty of Medicine, Aalborg University, Fredrik Bajers Vej 7D-3, 9220 Aalborg E, Denmark. Tel.: +45 9940 9832; fax: +45 9815 4008. E-mail address: (T. Graven-Nielsen).

Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.

Supplemental digital content is available for this article. Direct URL citations appear in the printed text and are provided in the HTML and PDF versions of this article on the journal's Web site (

Received May 03, 2018

Received in revised form July 11, 2018

Accepted July 17, 2018

© 2018 International Association for the Study of Pain
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