EffectofDeepIntramuscularStimulationandTranscranialMagneticStimulationonNeurophysiologicalBiomarkersinChronicMyofascialPainSyndrome

Chronic myofascial pain syndrome (MPS) is a common and debilitating condition characterized by trigger points and associated with both peripheral and central sensitization. Despite its prevalence, the underlying neurobiological mechanisms remain incompletely understood, and effective treatments are needed. Previous research suggested that neuromodulatory techniques targeting either the central nervous system (repetitive transcranial magnetic stimulation, or rTMS) or the periphery (deep intramuscular stimulation therapy, or DIMST) could provide pain relief in various chronic pain conditions. However, it was unclear whether combining these top-down and bottom-up approaches would produce synergistic effects, and whether any clinical improvements would be reflected in measurable biomarkers related to neuroplasticity, inflammation, oxidative stress, or cellular damage.

The researchers conducted a randomized, double-blind, factorial, placebo-controlled clinical trial at a university hospital in Brazil. They recruited 46 women aged 19 to 75 years with diagnosed chronic MPS. Participants were randomly assigned to one of four groups: rTMS plus DIMST (active both), rTMS plus sham-DIMST, sham-rTMS plus DIMST, or sham-rTMS plus sham-DIMST (double placebo). All participants received 10 treatment sessions, each lasting 20 minutes, over approximately two weeks. rTMS was delivered at 10 Hz frequency at 80% resting motor threshold over the left primary motor cortex.

DIMST involved electroacupuncture needles placed in paraspinal muscles at dermatomes corresponding to C2-C5, with 2 Hz electrical stimulation. Sham procedures used inactive coils or disconnected electroacupuncture devices with visible/audible cues to maintain blinding. Pain was measured using a 10-cm visual analogue scale (VAS) before and after each session. Neurophysiological assessments included motor evoked potentials (MEP), short intracortical inhibition (SICI), intracortical facilitation (ICF), and cortical silent period (CSP) using transcranial magnetic stimulation.

Blood samples were collected at baseline, day 5, and day 10 to measure brain-derived neurotrophic factor (BDNF), S100b, lactate dehydrogenase (LDH), inflammatory cytokines (TNF-α, IL-6, IL-10), and oxidative stress parameters (SOD, catalase, GPx, protein carbonyls, ROS).

For pain relief, all three active treatment groups (rTMS+DIMST, rTMS+sham-DIMST, and sham-rTMS+DIMST) showed significantly lower VAS scores compared to the double sham group. Specifically, for VAS assessed immediately before each session, there was a significant treatment effect (P<0.05, F(1,3)=3.494) and time effect (P<0.05, F(1,9)=7.55), with the sham-rTMS+DIMST group showing lower pain than sham-rTMS+sham-DIMST. For VAS assessed immediately after each session, there was again a significant treatment effect (P<0.05, F(1,3)=4.656) and time effect (P<0.05, F(1,9)=2.68), with all three active groups showing lower pain than the double sham group. The calculated effect size f was 0.53 for before-treatment VAS and 0.56 for after-treatment VAS, with post hoc power of 0.99.

Importantly, there was no synergistic effect from combining rTMS and DIMST — the combination was not superior to either treatment alone. For neurophysiological parameters, there was a significant treatment-by-time interaction for MEP (P<0.05), with increased MEP amplitude after rTMS+sham-DIMST compared to pretreatment, and a trend toward increase after rTMS+DIMST (P=0.08). No changes were found in SICI, ICF, or CSP (P>0.05). For biochemical parameters, none of the interventions changed serum BDNF, inflammatory markers (TNF-α, IL-6, IL-10), oxidative stress parameters (protein carbonyls, ROS, SOD, catalase, GPx), S100b, or LDH (all P>0.05).

No serious or moderate side effects were observed.

Both central (rTMS) and peripheral (DIMST) neuromodulation effectively reduce pain in chronic MPS patients, but their combination does not provide additional benefit beyond either treatment alone. This suggests that these techniques may share overlapping analgesic pathways, possibly involving descending inhibitory systems. The increase in MEP amplitude with rTMS indicates enhanced corticospinal excitability, which may relate to its analgesic mechanism. However, the lack of change in peripheral biomarkers — including those related to neuroplasticity, inflammation, oxidative stress, and cellular damage — suggests that the clinical pain relief occurs through mechanisms not captured by these serum measures, or that any peripheral biochemical changes are too subtle to detect in blood.

For patients, this means that either rTMS or DIMST could be reasonable treatment options, but combining them is unlikely to provide extra benefit. For clinicians, the findings support the safety of these neuromodulatory approaches and highlight the importance of neurophysiological assessment in understanding treatment mechanisms, while cautioning against expecting synergistic effects from multimodal neuromodulation in MPS.