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

Abstract

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.

Masseter corticomotor excitability is decreased after intramuscular administration of nerve growth factor

“…Particularly, the increased corticomotor excitability is not generally evident after the first injection of NGF in those studies. This complex dynamic relationship between corticomotor facilitation and inhibition has been demonstrated (De Martino, Zandalasini, et al, ) and it is also presupposed by the most recent models concerning the relationship between pain and motor function (Hodges & Smeets, ; Hodges & Tucker, ), (c) the functional and motor control differences between the upper limb muscles and the jaw muscles. The masseter is a jaw closing muscle that is mostly related with the rhythmic movements of mastication and, therefore, its motor output is subjected to complex modulatory controls (Lund, ).…”

“…Overall, our findings that suggest decreased corticomotor excitability direct oppose the vicious cycle theory (Travell et al, ). Nonetheless, recent studies have presented the opposite effect for the spinal innervation, i.e., increased corticomotor excitability following repeated injections of NFG into the extensor carpi radialis brevis (ECRB), which is likely explained as a motor learning effect that results from the search for a new moment strategy in the affected limb (De Martino, Seminowicz, Schabrun, Petrini, & Graven‐Nielsen, ; De Martino, Zandalasini, Schabrun, Petrini, & Graven‐Nielsen, ; Schabrun, Christensen, Mrachacz‐Kersting, & Graven‐Nielsen, ). There are some important methodological differences that could account for these contradictory findings, besides the need of the above‐mentioned pre‐activation level: (a) the tonic muscle contractions could have facilitated nociceptive inputs in the NGF injected masseter.…”

“…Interestingly, when eccentric exercises were applied in NGF‐sensitized ECRB, such combined effect results in decreased cortical excitability that is most probably driven by neural protective mechanisms (De Martino, Zandalasini, et al, ). In addition, tonic infusion of hypertonic saline or muscle soreness induced by eccentric exercises in the upper limbs is also related with reduced corticomotor output (De Martino, Petrini, Schabrun, & Graven‐Nielsen, ; Le Pera et al, ; Schabrun, Burns, & Hodges, ).…”

High frequency repetitive transcranial magnetic stimulation to the left dorsolateral prefrontal cortex modulates sensorimotor cortex function in the transition to sustained muscle pain

“…Using a TMS intensity of 120% rMT, the motor cortical map was established based on MEPs evoked every 6 s with a total of 5 stimuli at each site on the stimulation grid De Martino et al, 2018). All grid sites were pseudo randomly stimulated from the hotspot until no MEP was recorded (defined as <50 µV peak-to-peak amplitude) in all five stimuli at all border sites .…”

End points for sickle cell disease clinical trials: patient-reported outcomes, pain, and the brain

“…Grip force strength. Grip force strength can be measured as a nonevoked quantitative measure and has been used to assess sustained muscle pain in experimental muscle hyperalgesia in healthy subjects induced by nerve growth factor 180 ; however, weak muscle performance, myalgia, and motivation of the patient may influence outcomes. Table 2 presents the pain panel's recommendations for prioritization, recognizing that the gold standard for pain assessment is patient report.…”