Left dorsolateral prefrontal cortex repetitive transcranial magnetic stimulation reduces the development of long-term muscle pain

Abstract

The left dorsolateral prefrontal cortex (DLPFC) is involved in the experience and modulation of pain, and may be an important node linking pain and cognition. Repetitive transcranial magnetic stimulation (rTMS) to the left DLPFC can reduce chronic and experimental pain. However, whether left DLPFC rTMS can influence the development of chronic pain is unknown. Using repeated intramuscular injection of nerve growth factor to induce the development of sustained muscle pain (lasting weeks), 30 healthy individuals were randomized to receive 5 consecutive daily treatments of active or sham left DLPFC rTMS, starting before the first nerve growth factor injection on day 0. Muscle soreness and pain severity were collected daily for 14 days and disability on every alternate day. Before the first and 1 day after the last rTMS session, anxiety, depression, affect, pain catastrophizing, and cognitive performance on the attention network test were assessed. Left DLPFC rTMS treatment compared with sham was associated with reduced muscle soreness, pain intensity, and painful area (P < 0.05), and a similar trend was observed for disability. These effects were most evident during the days rTMS was applied lasting up to 3 days after intervention. Depression, anxiety, pain catastrophizing, and affect were unchanged. There was a trend toward improved cognitive function with rTMS compared with sham (P = 0.057). These data indicate that repeated left DLPFC rTMS reduces the pain severity in a model of prolonged muscle pain. The findings may have implications for the development of sustained pain in clinical populations.

Non-invasive Motor Cortex Neuromodulation Reduces Secondary Hyperalgesia and Enhances Activation of the Descending Pain Modulatory Network

“…However, we know of only six studies investigating the effect of non-invasive neuromodulatory techniques on persistent or repetitive pain models in healthy subjects. Only two of these studies targeted M1 (Tamura et al, 2004; Ihle et al, 2014), while others targeted the DLPFC (Fierro et al, 2010; Taylor et al, 2013; Lin et al, 2017; Seminowicz et al, 2018).…”

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

“…The study was approved by the local Ethics Committee (N-20170041) and was performed in accordance with the Helsinki Declaration. Other findings of this protocol are published elsewhere and include effects of rTMS on pain, muscle soreness, disability, painful area, and cognitive task performance (Seminowicz et al, 2018).…”

Grand Challenges in Musculoskeletal Pain Research: Chronicity, Comorbidity, Immune Regulation, Sex Differences, Diagnosis, and Treatment Opportunities

“…The current treatment provides some relief of acute or short-lasting pain but is unsatisfactory for chronic musculoskeletal pain (78)(79)(80)(81). A recent report showed that transcranial magnetic stimulation of the prefrontal cortex attenuated long-term experimental muscle pain in human subjects (14).…”

“…A limitation of these models, however, is that the induced muscle pain hypersensitivity would resolve within minutes to hours [e.g., ( 5 , 12 )]. Nerve growth factor induces relatively long-lasting hyperalgesia for 4–7 days to a few weeks after injection into the muscle in humans ( 9 , 13 , 14 ). Chronic pain is defined as pains that persist or recur for longer than 3 months ( 15 ).…”