Anodal transcranial direct current stimulation over the primary motor cortex attenuates capsaicin‐induced dynamic mechanical allodynia and mechanical pain sensitivity in humans

Abstract

Background Anodal transcranial direct current stimulation over the primary cortex has been shown to activate regions of the brain involved in the descending modulation of pain sensitivity. However, more research is required to dissect the spinal cord analgesic mechanisms associated with the development of central sensitization. Methods In this randomized, double blind, crossover study 12 healthy participants had baseline mechanical stimulus response (S/R) functions measured before and after the development of capsaicin‐induced ongoing pain sensitivity. The effects of 20 min of either real or sham transcranial direct current stimulation (tDCS, 2 mA) over the primary motor cortex on dynamic mechanical allodynia (DMA) and mechanical pain sensitivity (MPS) were then investigated. Results Topical application of capsaicin resulted in an increase in area under the pain ratings curve for both DMA (p < .01) and MPS (p < .01). The effects of tDCS on the area under the curve ratio (i.e. post‐/pre‐treatment) revealed significant analgesic effects over DMA (p < .05) and MPS (p < .05) when compared with sham. Conclusions This study demonstrates that anodal tDCS over the primary motor cortex can reduce both dynamic and static forms of mechanical pain sensitivity associated with the development of DMA and MPS, respectively. The use of tDCS may provide a novel mechanism‐driven therapy in chronic pain patients with altered mechanical S/R functions. Significance This research shows new evidence that anodal tDCS over the primary motor cortex can reduce dynamic and static forms of mechanical pain sensitivity in the capsaicin model of ongoing pain. By using this approach, it may be possible to provide mechanism‐driven analgesia in chronic pain patients who have dynamic mechanical allodynia and/or secondary mechanical hyperalgesia.

During capsaicin‐induced central sensitization, brush allodynia is associated with baseline warmth sensitivity, whereas mechanical hyperalgesia is associated with painful mechanical sensibility, anxiety and somatization

“…However, this will likely require larger sample sizes, genetic analysis and a closer inspection of receptor mechanisms at the site of capsaicin exposure. Potential implications for treatment include that treatments for allodynia likely need to target peripheral or spinal mechanisms, whereas secondary hyperalgesia is susceptible to cortical stimulation and cognitive behavioural treatments targeting anxiety (Hughes et al, 2020;Meeker et al, 2019;Salomons et al, 2014).…”

“…Specifically, state anxiety enhances attentional capture of painful stimuli and brief cognitive behavioural interventions have been shown to decrease the area of secondary hyperalgesia after capsaicin exposure. Furthermore, noninvasive brain stimulation of the cortex in healthy subjects ameliorates capsaicin-driven secondary hyperalgesia (Gregoret et al, 2021;Hughes et al, 2020;Meeker et al, 2019;Seifert et al, 2010). Also of note, there was no correlation between PCS and mechanical hyperalgesic magnitude.…”

Brain Circuits Involved in the Development of Chronic Musculoskeletal Pain: Evidence From Non-invasive Brain Stimulation

“…In line with previous findings, Hughes et al showed that compared to sham, active tDCS over M1 significantly reduced dynamical mechanical allodynia and mechanical pain sensitivity initiated by capsaicin-induced pain applied before tDCS in 12 healthy subjects. The authors concluded that M1 exhibits top-down modulation of inhibitory descending pathways to reduce the increased excitability in the dorsal horn, which has previously been associated with the development of allodynia ( 78 ).…”

“…Through the experimental application and manipulation of pain in healthy individuals, we can monitor the time course when pain develops and gradually resolves and relate these changes with other clinical or neural measures. Prolonged pain in healthy humans can mimic symptoms seen in chronic conditions such as increased pain sensitivity (hyperalgesia), increased sensitivity to sensory stimuli (allodynia), or muscle soreness ( 77 , 78 ).…”

Effects of multifocal transcranial direct current stimulation targeting the motor network during prolonged experimental pain

“…Previous results on tDCS analgesia are controversial (Mylius et al, 2012). Whereas a recent study showed that one session of anodal M1 tDCS reduced dynamic mechanical allodynia and secondary mechanical hyperalgesia (Hughes et al, 2020) due to 1% capsaicin, suggesting that tDCS may act on sensitized pathways, a number of tDCS (Borckardt et al, 2012;Jürgens et al, 2012;Lefaucheur et al, 2017) and rTMS (Bradley et al, 2016;Sacco et al, 2014) studies found that one session of non-invasive brain stimulation does not genuinely elicit analgesia in healthy individuals. Importantly, the present study was not powered to investigate pain sensitivity as a primary outcome.…”