Intramuscular electrical stimulus potentiates motor cortex modulation effects on pain and descending inhibitory systems in knee osteoarthritis: a randomized, factorial, sham-controlled study

Maria da Graca-Tarragó, Mateus Lech, Letícia Dal Moro Angoleri, Daniela Silva Santos, Alícia Deitos, Aline Patrícia Brietzke, Iraci Ls Torres, Felipe Fregni, Wolnei Caumo, Maria da Graca-Tarragó, Mateus Lech, Letícia Dal Moro Angoleri, Daniela Silva Santos, Alícia Deitos, Aline Patrícia Brietzke, Iraci Ls Torres, Felipe Fregni, Wolnei Caumo

Abstract

Background: Neuroplastic changes in nociceptive pathways contribute to severity of symptoms in knee osteoarthritis (KOA). A new look at neuroplastic changes management includes modulation of the primary motor cortex by transcranial direct current stimulation (tDCS).

Objectives: We investigated whether tDCS combined with intramuscular electrical stimulation (EIMS) would be more efficacious than a sham (s) intervention (s-tDCS/s-EIMS) or a single active(a)-tDCS/s-EIMS intervention and/or s-tDCS/a-EIMS in the following domains: pain measures (visual analog scale [VAS] score and descending pain modulatory system [DPMS], and outcomes, and analgesic use, disability, and pain pressure threshold (PPT) for secondary outcomes.

Registration: The trial is registered in Clinicaltrials.gov: NCT01747070.

Methods: Sixty women with KOA, aged 50-75 years old, randomly received five sessions of one of the four interventions (a-tDCS/a-EIMS, s-tDCS/s-EIMS, a-tDCS/s-EIMS, and s-tDCS/a-EIMS). tDCS was applied over the primary motor cortex (M1), for 30 minutes at 2 mA and the EIMS paraspinal of L1-S2.

Results: A generalized estimating equation model revealed the main effect of the a-tDCS/a-EIMS in the VAS pain scores at end treatment compared with the other three groups (P<0.0001). There existed a significant effect of time and a significant interaction between group and time (P<0.01 for both). The delta-(Δ) pain score on VAS in the a-tDCS/a-EIMS group was -3.59, 95% CI: -4.10 to -2.63. The (Δ) pain scores on VAS in the other three groups were: a-tDCS/s-EIMS=-2.13, 95% CI: -2.48 to -1.64; s-tDCS/a-EIMS=-2.25, 95% CI: -2.59 to -1.68; s-tDCS/s-EIMS MR =-1.77, 95% CI: -2.08 to -1.38. The a-tDCS/a-EIMS led to better effect in DPMS, PPT, analgesic use, and disability related to pain.

Conclusion: This study provides additional evidence regarding additive clinical effects to improve pain measures and descending pain inhibitory controls when the neuromodulation of the primary motor cortex with tDCS is combined with a bottom-up modulation with EIMS in KOA. Also, it improved the ability to walk due to reduced pain and reduced analgesic use.

Keywords: CPM; conditioned pain modulation; electroacupuncture; osteoarthritis; pain pressure threshold; tDCS; transcranial direct current stimulation.

Conflict of interest statement

Disclosure The authors report no conflicts of interest in this work.

Figures

Figure 1
Figure 1
Flowchart showing recruitment and progress through the study. Abbreviations: a, active; BDI, Beck Depression Inventory; BP-PCS, Brazilian Portuguese pain catastrophizing scale; CPM, conditioned pain modulation; EIMS, intramuscular electrical stimulation; PPT, pain pressure threshold; PSQI, Pittsburgh Sleep Quality Index; tDCS, transcranial direct current stimulation; s, sham; VAS, visual analog scale; WOMAC, Western Ontario and McMaster Universities Index.
Figure 2
Figure 2
Pain scores reported on visual analog scale measured daily in the knee to which the a-EIMS or s-EIMS was applied. Notes: Data are presented as mean (SEM). Numbers positioned above the symbols indicate difference between the interventions groups at time point compared by GEE model followed by the Bonferroni test for post hoc multiple comparisons. Abbreviations: a, active; D, day; EIMS, intramuscular electrical stimulation; GEE, generalized estimating equations; s, sham; tDCS, transcranial direct current stimulation; VAS, visual analog scale.
Figure 3
Figure 3
The change in NPS 0–10 during CPM task, before treatment and at end of treatment in the four experimental groups. Notes: The error bars indicate standard error of the mean. Numbers show differences between four treatment groups. All comparisons were performed by a GEE, followed by the Bonferroni test for post hoc multiple comparisons. Abbreviations: a, active; CPM, conditioned pain modulation; EIMS, intramuscular electrical stimulation; GEE, generalized estimating equations; NPS, numerical pain scale; s, sham; tDCS, transcranial direct current stimulation.
Figure 4
Figure 4
Scatterplot of the correlation between BDNF and pain pressure threshold in the intervention group (n=60). Abbreviations: BDNF, brain-derived neurotrophic factor.

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