Chronic pain is one of the most prevalent and disabling health problems worldwide. According to World Health Organization data, it affects between 20% and 30% of the adult population and represents one of the leading causes of functional disability. When conventional pharmacological approaches prove insufficient or generate significant adverse effects, non-invasive brain stimulation (NIBS) techniques can offer a complementary alternative with a favourable safety profile.
This article reviews the foundations, scientific evidence and clinical applications of the three main NIBS modalities in the context of chronic pain: repetitive transcranial magnetic stimulation (rTMS), transcranial direct current stimulation (tDCS) and transcranial alternating current stimulation (tACS).
To understand the role of NIBS in pain management, it is essential to distinguish between the two main types of chronic pain:
Nociceptive pain originates from activation of peripheral nociceptors in response to potentially harmful stimuli (mechanical, thermal or chemical). It is the “typical” pain associated with inflammatory processes, musculoskeletal trauma or tissue injuries. The mechanisms of transduction, transmission and modulation of the pain signal function physiologically, and pain fulfils a protective function.
Neuropathic pain, in contrast, results from injury or dysfunction of the somatosensory nervous system itself, either at peripheral level (diabetic neuropathy, post-herpetic neuralgia, carpal tunnel syndrome) or central level (post-stroke pain, pain associated with spinal cord injury, pain in multiple sclerosis). It is characterised by symptoms such as allodynia (pain from non-painful stimuli), hyperalgesia, dysaesthesias and burning or electric-shock sensations. Its pathophysiology involves central sensitisation with reorganisation of the cortical and thalamic pain-processing circuits.
This distinction is relevant because NIBS techniques act primarily on the central mechanisms of pain processing and modulation. For this reason, the most robust scientific evidence is concentrated in pain of neuropathic origin, where central sensitisation plays a predominant role. Nevertheless, there is growing interest in their complementary application in syndromes such as fibromyalgia, chronic low back pain and complex regional pain syndrome (CRPS), in which alterations in cortical excitability have also been identified.
rTMS uses a magnetic field generated by a coil placed over the scalp to induce electrical currents in specific cortical regions. The principle is based on Faraday's law of electromagnetic induction: a varying magnetic field generates an electric current in a nearby conductor (in this case, cortical neurons).
The most studied therapeutic target for pain is the primary motor cortex (M1) contralateral to the affected side. The analgesic mechanism of M1 stimulation is not explained by direct motor activation, but by modulation of descending cortico-subcortical circuits that include:
Stimulation parameters determine the neurophysiological effect: high frequencies (≥5 Hz) generate an excitatory effect, while low frequencies (≤1 Hz) produce an inhibitory effect. The most commonly used protocols for pain employ high-frequency stimulation (10–20 Hz) over contralateral M1.
High-frequency rTMS over M1 has the highest level of evidence among NIBS techniques for neuropathic pain. The European Federation of Neurological Societies (EFNS) guidelines and the international consensus guidelines updated by Lefaucheur et al. (2020) establish:
A meta-analysis published in The Journal of Pain by O'Connell et al. (2018) confirmed a statistically significant analgesic effect of active rTMS versus sham stimulation in patients with neuropathic pain, with a moderate effect size. The Cochrane review on non-invasive brain stimulation for chronic pain (O'Connell et al., 2014, updated 2018) concluded that there is moderate-quality evidence in favour of high-frequency rTMS over M1 for short-term reduction of neuropathic pain.
The most relevant randomised clinical trials have demonstrated reductions of between 20% and 40% on the visual analogue scale (VAS) for pain in responders. However, evidence indicates that the response is variable between individuals and that effects tend to be more pronounced in neuropathic pain of central origin (such as post-stroke pain) than in peripheral neuropathic pain.
tDCS applies a low-intensity continuous electric current (usually between 1 and 2 mA) through two electrodes placed on the scalp. Unlike rTMS, tDCS does not directly induce action potentials, but rather modifies the resting potential of neuronal membranes, facilitating or hindering depolarisation depending on the polarity of stimulation:
For chronic pain, the most commonly used montage is anodal stimulation over contralateral M1 to the painful side, with the cathode usually over the contralateral supraorbital cortex. Proposed analgesic mechanisms include modulation of thalamo-cortical circuits, facilitation of descending inhibitory pathways and changes in synaptic plasticity mediated by NMDA receptors and release of BDNF (brain-derived neurotrophic factor).
The guidelines of Lefaucheur et al. (2017, updated 2020) establish for tDCS:
A meta-analysis by Vaseghi et al. (2014) including 13 placebo-controlled trials found a significant analgesic effect of active tDCS compared with sham stimulation, in both neuropathic pain and fibromyalgia. Subsequent systematic reviews, including that of Zortea et al. (2019), have confirmed these findings, although noting considerable heterogeneity between studies regarding protocols, duration of effects and populations included.
tDCS presents some practical advantages over rTMS: the equipment is smaller and less costly, application is simpler and it can be combined simultaneously with rehabilitation activity (for example, during physiotherapy or occupational therapy sessions). This possibility of concurrent use with motor training is particularly interesting in the neurorehabilitation context.
tACS is the most recent of the three modalities and uses an oscillating alternating current that varies sinusoidally at a specific frequency. Its mechanism of action is based on the phenomenon of oscillatory entrainment: the externally applied current can synchronise endogenous neural rhythms to the stimulation frequency, thereby modulating cortical oscillatory dynamics.
The interest of tACS in pain lies in the fact that chronic pain states are associated with alterations in brain oscillatory patterns. Increases in theta band power (4–8 Hz) in the somatosensory and cingulate cortex, as well as reduced alpha activity (8–12 Hz) in parietal regions, have been documented in patients with chronic neuropathic pain. This pattern, termed thalamocortical dysrhythmia, constitutes a potential target for tACS.
Experimental protocols for pain typically employ stimulation in the alpha band (10 Hz) over the somatosensory or motor cortex, seeking to restore reduced alpha rhythms and thereby normalise sensory pain processing.
tACS is the technique with the least volume of evidence of the three, although preliminary results are promising. Pilot studies such as that of Ahn et al. (2019) have demonstrated that tACS at 10 Hz over the somatosensory cortex can significantly reduce pain perception in patients with chronic low back pain, with effects correlating with an increase in alpha power on EEG. A randomised controlled trial by Arendsen et al. (2018) found similar results in peripheral neuropathic pain.
Although the level of evidence is still lower than that of rTMS and tDCS, tACS offers a conceptually different approach —focused on the modulation of brain rhythms— that makes it an active field of research with therapeutic potential in the management of chronic pain.
| Feature | rTMS | tDCS | tACS |
|---|---|---|---|
| Type of stimulus | Magnetic pulses | Continuous direct current | Oscillatory alternating current |
| Focality | High (1–2 cm²) | Low–moderate | Low–moderate |
| Depth of action | Up to 2–3 cm | Predominantly superficial | Predominantly superficial |
| Level of evidence in neuropathic pain | Level A (EFNS) | Level B (EFNS) | Preliminary |
| Equipment cost | High | Low–moderate | Low–moderate |
| Concurrent use with rehabilitation | Limited | Possible | Possible |
According to available evidence and clinical practice guidelines, the main indications of NIBS in the context of chronic pain include:
NIBS techniques are considered generally safe when applied within the parameters established by international safety guidelines (Rossi et al., 2021; Antal et al., 2017).
Risk-benefit assessment must be performed on an individual basis by a professional experienced in neuromodulation, taking into account the patient's complete clinical history and established therapeutic objectives.
At GNeuro, a robotic neurorehabilitation centre located in Ourense, non-invasive brain stimulation is integrated within a multimodal and individualised rehabilitation model. Our approach is based on three principles:
The combination of NIBS with intensive robotic training can contribute to optimising neuroplasticity mechanisms, facilitating motor relearning and modulation of pain-processing circuits. This synergy between neuromodulation and high-intensity rehabilitation represents one of the lines of work that the most recent scientific evidence identifies as promising in the management of chronic pain of neurological origin.
Is non-invasive brain stimulation painful?
Non-invasive brain stimulation (both rTMS and tDCS and tACS) is generally well tolerated. rTMS may produce a mild tapping sensation on the scalp during the session, while tDCS usually generates a slight tingling or itching under the electrodes. tACS produces sensations similar to tDCS. These effects are usually transient and disappear at the end of stimulation. Most patients complete the protocols without needing to interrupt sessions.
How many sessions of rTMS or tDCS are needed to notice an improvement in pain?
Standard rTMS protocols for pain comprise between 5 and 10 consecutive daily sessions, with subsequent maintenance sessions. tDCS is usually applied in blocks of 5 to 10 sessions. Available evidence suggests that analgesic effects may begin to manifest after the first 3 to 5 sessions, although the response is variable and depends on individual factors such as pain type, chronicity and personal response.
Does non-invasive brain stimulation replace other pain treatments?
No. Non-invasive brain stimulation is conceived as a complementary tool within an individualised rehabilitation programme. It is used in combination with physiotherapy, occupational therapy, pharmacological management and other interventions the clinical team considers indicated. Scientific evidence supports it as a complement that can contribute to improving overall treatment outcomes.
What is the difference between rTMS, tDCS and tACS?
rTMS (repetitive transcranial magnetic stimulation) uses magnetic pulses to modulate cortical activity, with greater focality and ability to reach deeper structures. tDCS (transcranial direct current stimulation) applies a weak constant electric current to modify neuronal excitability. tACS (transcranial alternating current stimulation) uses oscillating alternating currents to modulate brain rhythms. Each technique has specific indications and advantages depending on the patient's clinical condition.
At GNeuro we evaluate each case individually to determine which neurorehabilitation approach may be most appropriate. If you would like more information about our programmes, do not hesitate to contact us.
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