Chronic musculoskeletal pain is the main cause of living with disability worldwide. Yet, one of the major problems in planning new therapeutic strategies is that the underlying mechanisms driving pain are not completely understood. Recently, pain researches have highlighted the role of central nervous system in maintaining pain chronicity, due to maladaptive pain-related neuroplasticity. However, it is still unknown how maladaptive pain-related neuroplasticity is altered during the transition from acute to chronic pain and at what time-point changes develop.
Therefore, the first aim of the present Ph.D. project was to investigate the nature and time-course of pain-related neuroplasticity provoked by experimental long-lasting muscle pain in healthy volunteers. In addition, neuromodulatory interventions have been recently proposed to treat chronic musculoskeletal pain. Consequently, the second aim of this project was to modulate the cortical excitability changes and the clinical manifestations provoked by experimental long-lasting muscle pain applying multiple sessions of repetitive transcranial magnetic stimulation (rTMS) to the left dorsolateral prefrontal cortex (DLPFC).
The results of the first two studies suggested that muscle pain induced by delayed-onset muscles soreness (DOMS), intramuscular injections nerve growth factor (NGF) and the two models combined are able to provoke long-lasting muscle pain up to 20 days, muscle hyperalgesia and functional disability. Moreover, temporary cortical excitability changes have been probed: While DOMS inhibited the cortico- motor excitability, intramuscular injections of NGF facilitated it. Addition- ally, in- tramuscular injections of NGF modified both frontal and centro-parietal sensory cortical excitability while DOMS modified only centro-parietal sensory cortical ex- citability. In conclusion, these findings suggest that DOMS and muscle pain induced by NGF provoked different cortical sensorimotor adaptations.
The results from the third study showed that multiple sessions of 10 Hz rTMS to the left DLPFC were able to modulate the corticomotor and sensory cortical adap- tations during muscle pain induced by intramuscular injections NGF, as well as re- duced hyperalgesia, pain intensity and functional disability.
In conclusion, the results of this Ph. D. project showed promising findings regarding the opportunity to modulate pain-induced neuroplasticity as well as analgesic ef- fects of 10 Hz rTMS to the left DLPFC.