FormalPara Key Summary Points

Equistasi® is a novel device delivering a focal microvibration of about 9000 Hz, which is not perceived by the patient.

The device is a little plate that is attached to the skin and activated by body temperature.

Focal microvibrations were found to be effective in the management of chronic pain of different origins.

Further studies should be conducted to elucidate the mechanism of action of focal microvibrations.

Introduction

Chronic pain is defined as a pain lasting more than 3–6 months; it represents an important physical and emotional burden for the patient with a dramatic impact on quality of life [1]. Its incidence is about 30% in the general population, and it is one of the most important causes of medical consultation; moreover, it also represents a relevant socio-economical issue with an estimated loss of working days per year of 4 million only for back pain, accounting for productivity and medical costs from $560 to $635 billion in 2010 in the United States [2]. In addition, even if they are present at work, people suffering from chronic pain are often unable to completely fulfill their tasks [3, 4].

The management of chronic pain should strive not only to reduce pain intensity but also to enhance functional capacity, social relationships, mood, and sleep. All these factors are influenced by pain and collectively contribute to determining the overall quality of life [5, 6]. Patients with a history of a long-lasting pain often experience depression, anxiety, and anger, and show a reduced coping capacity with a higher incidence of negative thoughts and catastrophizing attitude. Psychological elements that could significantly contribute to pain perception are meaning assigned to the suffering, degree of perceived control, perceived social support, fear of pain, pain attention pattern, and previous experiences of pain [7].

Pharmacological treatments are usually the first-line approach, but the adverse effects of analgesic drugs often hinder the possibility to increase the dosage to achieve an adequate clinical response; furthermore, patients’ comorbidities (e.g., renal, cardiovascular, and respiratory diseases) could limit the use of many medications such as non-steroidal anti-inflammatory drugs and opioids. Patients can also benefit from minimally invasive techniques for reducing or eliminating the use of analgesic drugs and, consequently, their adverse effects [8]. On the other hand, minimally invasive procedures have important drawbacks such as X-ray exposition, bleeding, nerve injury, and their results are strictly dependent on the expertise of the operator [9,10,11].

Vibratory analgesia is one of the non-pharmacological tools that is able to reduce pain through the application of cutaneous vibrations; its mechanism of action has not yet been explained, even if its effectiveness has been proven in both clinical and experimental conditions. Two theories have been proposed: the first hypothesizes a central role of wide dynamic range neurons at a spinal level whose role in the transmission of pain signal would be influenced by the peripheral stimuli coming from mechanoreceptors; another theory relies on the involvement of higher nervous centers in the somatosensory cortex (i.e., 3a and 3b/1 areas) whose interaction would produce a suppression of painful signals processing [12].

Equistasi® is a novel device that consists of a small and light rectangular plate (10 × 20 × 0.5 mm, 0.17 g); once the device is in contact with the skin, it transforms the thermal energy of the body into vibrations characterized by a frequency of about 9000 Hz and a maximum length of 0.02 mm, so they are harmless and not felt by the patient (Fig. 1) [13]. Equistasi® has proven to be effective in gait and balance control in patients affected by Parkinson’s disease, multiple sclerosis, and ataxia; its potential for managing chronic pain has not yet been investigated [14,15,16,17,18,19,20,21,22]. In this work, our aim is to evaluate the effects of Equistasi® on chronic pain of different origins and its influence on quality of life.

Fig. 1
figure 1

The Equistasi® device

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Methods

This is a pilot study conducted according to the guidelines of the Declaration of Helsinki and approved by the Ethics Committee of University of Naples “Federico II” (IRB protocol number: 307/21). Informed consent was obtained from all subjects involved in the study. Inclusion criteria were: age more than 18 years, pain lasting more than 6 months, nociceptive or neuropathic pain due to musculoskeletal disease, myofascial pain, post herpetic neuralgia, low back pain due to facet joint syndrome, sacroiliitis, or discal hernia with or without radiculopathy; and pain intensity measured with numeric rating scale (NRS) ≥ 4. Exclusion criteria were: psychiatric disease, diseases characterized by spasticity such as Parkinson’s disease, multiple sclerosis, stroke, spinal cord lesions; patients with implantable device for spinal cord stimulation, peripheral nerve electric neuromodulation or dorsal root ganglion stimulation; patients who underwent central or peripheral electric neuromodulation in the previous 3 months; cancer patients; fibromyalgia patients; or patients with a history of central nervous system surgery. Patients suffering from Parkinson’s disease were excluded because they have been proved to take benefit from the device in terms of gait and rigidity improvement, so this beneficial effect could influence their judgment about the amelioration of their quality of life due to pain relief; moreover, diseases affecting the structure of the nervous system or treatments influencing the stimulus conduction through the nervous routes were included in the exclusion criteria, as they might affect the potential mechanism of action of Equistasi® which, even if unknown, is probably due to the transmission of the vibrating energy through the nervous system.

Procedure

After signing an informed consent form, patients were randomized in an interventional (group E) and a control (group C) group, with each group consisting of 30 patients. Group E underwent pain mapping by a trained physician to determine the correct position of Equistasi®; each patient was treated with the application of three or four devices; the number of devices and the skin point where they were applied were different according to the extension and the localization of the pain; the devices were positioned on the skin surface correspondent to the localization of the pain generator and on the areas of referred or radiating pain; patients were told to apply Equistasi for 2 h in morning and 2 h in the evening. Group C was treated with standard pharmacological therapy consisting of gabapentinoids, opioids, non-steroidal anti-inflammatory drugs, and adjuvants (paracetamol, antidepressants, corticosteroids, local anesthetics, and anticonvulsants) according to the type and intensity of pain. Pain intensity and its influence on a patient’s life were evaluated by the Brief Pain Inventory (BPI), which is a multidimensional questionnaire exploring the influence of pain on general activity, mood, walking, working capacity, social relationships, sleep, and pleasure of living. BPI was administered at the baseline (T0), and after 7, 14, 30, 60, and 90 days of therapy (T7, T14, T30, T60, T90, respectively). For group E, the exact position of the devices was marked with a skin marker and the patient was provided with a skin marker to trace the initial signs when they faded; pharmacological therapy of group E did not change during the study period, and rescue therapy was ensured by paracetamol 1 g per os or tramadol 100 mg per os for a maximum of thrice daily. Patients’ functionality was evaluated through the Oswestry Disability Index (ODI), whereas the Working Ability Index (WAI) was used to investigate the influence of pain on patient working capacity; the above-mentioned questionnaires were administered to the enrolled patients at T0, T7, T14, T30, T60, and T90.

Our primary outcome was the change of pain intensity during the follow-up evaluated using BPI; the secondary outcomes were the changes in pain interference in all the different fields of a patient’s life such as general activity, mood, walking and working capacity, social relationships, sleep, and pleasure of living evaluated with BPI; furthermore, additional secondary outcomes were the changes in disability and working ability investigated through ODI and WAI questionnaire, respectively.

Statistical Analysis

Data were presented as mean and standard deviation when normally distributed and as median and interquartile range if non-parametric; normal distribution of data was assessed through Shapiro–Wilk test. Parametric data were analyzed by analysis of variance (ANOVA) if parametric and with Friedman test if non-parametric and post hoc analysis were performed with Tukey test and Dunn's test, respectively. Comparisons between group E and group C were performed with Mann–Whitney test for non-parametric data and with unpaired Student’s t test for normally distributed data. Differences were considered statistically significant when p < 0.05. All the analyses were performed using R Studio version 2023.06.1 + 524 [23, 24].

Results

Table 1 reports the demographic data of our population: non-significant differences were recorded between group E and group C. Two patients in group E and one patient in group C were lost to follow-up.

Table 1 Demographic characteristics
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Table 2 shows the results of BPI score: in group E, the worst pain in the past 24 h significantly decreased at T15 compared to T0 (5.5 (3.25–6.75) vs. 8 (7–10), respectively, p < 0.05) and this finding persisted at T30, T60, and T90 compared to T0 (5 (3.25–6), 5 (3–6), 4 (3–5) vs. 8 (7–10), respectively; p < 0.001); the median score of average pain in the last 24 h was also lower at T15, T30, T60, and T90 compared to T0 (5 (3–5), 4.5 (3–5.75), 4 (2.75–5.25), 4 (2.5–5.5) compared to 6 (5–7), respectively; p < 0.05); current pain at the moment of the visit seemed to decrease during the follow-up from T0 to T90 (6 (4–7.5) vs. 3 (2–5), respectively), but it did not reach statistical significance. Pain interference on general activity, mood, waling ability, normal work, relations with other people, sleep, and enjoyment of life was significantly reduced in group E. Group C was characterized by no significant changes in all the fields explored by BPI during the follow-up.

Table 2 Brief Pain Inventory scores (median and IQR) recorded during the follow-up
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Table 3 shows that the reduction of pain intensity in group E was confirmed by ODI score even if the decreasing trend was less evident compared to that recorded by BPI: pain relief was statistically significant at T7, T30, T60, and T90 compared to T0 (2 (1–2), 2 (1–2.5), 2 (1–2), 1.5 (1–2) vs. 2.5 (2–3.75), respectively; p < 0.05). Lifting activity was also slightly improved at T30, T60, and T90 compared to T0 (2 (1–2), 2 (1–2), 1.5 (1–2) vs. 2 (2–3.75), respectively; p < 0.05) in group E. No differences during follow-up were recorded in ODI score of group C.

Table 3 Oswestry Disability Index scores (median and IQR) recorded during the follow-up
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Table 4 shows that the work ability in relation to demands improved at T7, T15, T30, T60, T90 compared to T0 (4 (3–4), 4 (4–4), 4 (4–4), 4 (3–4), 4 (3.25–4) vs. 3 (2–4), respectively; p < 0.05) for patients in group E, while no changes in WAI score were observed in group C.

Table 4 Work Ability Index scores (median and IQR) recorded during the follow-up
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Table 4 shows that the work ability in relation to demands improved at T7, T15, T30, T60, T90 compared to T0 (4 (3–4), 4 (4–4), 4 (4–4), 4 (3–4), 4 (3.25–4) vs. 3 (2–4), respectively; p < 0.05) for patients in group E, while no changes in WAI score were observed in group C.

We conducted a subgroup analysis of patients affected by osteoarticular and radicular pain, which represented the two most important painful conditions we treated with focal microvibration; patients affected by other pathologies were too few to conduct a significant analysis of the outcomes. For both osteoarticular and radicular pain, the worst pain in the last 24 h significantly reduced in the group E, whereas no changes were recorded in group C during the follow-up; average pain in the last 24 h significantly decreased during the follow-up in patients affected by osteoarticular pain, while, in radicular pain subgroup, current pain significantly lowered over time; also the interference of pain in daily life diminished as mood, walking ability, and sleep significantly improved in both subgroups with an additional improvement in normal work, relations, and enjoyment of life in the osteoarticular subgroup (Tables S1 and S2). ODI showed a significant improvement only in the intensity of pain for patients affected by osteoarticular pain (Tables S3 and S4), while none of the WAI items significantly changed during follow-up in either of the subgroups (Table S5 and S6).

Discussion

To our knowledge, this is the first study investigating the possible role of focal microvibration in the management of chronic pain caused by musculoskeletal disease, myofascial pain, post herpetic neuralgia, and low back pain due to facet joint syndrome, sacroiliitis, or discal hernia with or without radiculopathy. We found that focal microvibration delivered through Equistasi® is effective in reducing pain and it improved the quality of life of patients with a sustained beneficial effect, lasting through the 90 days of our follow-up; moreover, it showed a slight improvement in the work ability in relation to patient needs and in the ability to lift weights. These findings pave the way to other potential applications of this novel treatment, which was initially used in the treatment of walking impairment and loss of balance in many diseases such as multiple sclerosis, Parkinson’s disease, and in movement disorders related to cerebral infantile palsy.

Both the worst pain and the average pain in the last 24 h decreased from the baseline to the end of the study duration; it is noticeable that the maximum analgesic effect for both the above-mentioned parameters was reached after 15 days of treatment and even if the median score of pain after that time point seemed to decrease, the reduction was not statistically significant. These findings suggest that patients are likely to undergo a process of saturation of the system involved in the analgesic effect of Equistasi®. The same trend can be observed in the domain of BPI related to the aspects of patients’ everyday lives, such as general activity, mood, walking capacity, normal work, relations with other people, sleep, and enjoyment of life, which have been proven to be closely dependent on the intensity of pain. This finding is in agreement with the results of Chandrashekhar R et al.: the authors studied the effect of muscle focal vibration (which works with a higher energy and wider vibration which can be felt by the patient) on pain, balance, motility, and sensation in patients affected by diabetic peripheral neuropathy; the application of a pulsing or a sinusoidal vibration produced a better and prolonged beneficial effect on the aforementioned outcomes compared to a continuous vibration. The authors suggested that the latter vibration pattern could rapidly lead to a desensitization of the patient, thus reducing the advantageous effect of the intervention [25].

A remarkable finding was the reduction of analgesic drugs used by the patients to control their pain during the study period; this is a fundamental result, as Equistasi® can contribute to reduce the pharmacological burden and, consequently, drug-related adverse effects.

The reduction in pain intensity was confirmed by ODI score and, in addition, the capacity to lift weights was also improved; this latter finding corresponded to an increased work ability in relation to patient demand recorded by the WAI questionnaire.

The effects of vibration have been extensively investigated in the field of neurorehabilitation and its effectiveness has been proven in many conditions such as Charcot–Marie–Tooth 1A disease, Parkinson’s disease, stroke, and spinal cord injury [26, 27]. It was demonstrated that focal vibration can activate the somatosensory cortex and strengthen the connection between different areas of the brain, thus demonstrating an influence of the mechanical stimulation far from the point of its application [28]; notably, even subliminal vibrations (i.e., vibrations with an unperceivable intensity) are able to modify the activity of the sensory motor cortex, thus modulating its response to different stimuli [29]. Gate control theory has been hypothesized for vibrations with a frequency between 100 and 250 Hz applied in the same region of pain, contralaterally, or in the adjacent dermatomes [30,31,32,33]. Many other mechanisms have been advocated to explain the modulatory effect of mechanical vibrations on pain: some authors suggested a potential effect in the expression of neurotransmitters and neurohormones such as calcitonin gene-related peptide and substance P along with a downregulation of transient receptor vanilloid 1, thus accounting for a peripheral effect of the stimulation [34, 35]. Other studies pointed out the influence of focal vibrations on the production of pain-related hormones such as cortisol, whose levels are reduced by high-frequency stimulation at 300 Hz, and oxytocin, which increased in plasma and cerebrospinal fluid of experimental animals treated with a 100-Hz vibration; the analgesic effect of oxytocin was demonstrated by the reversal of its antinociceptive effect with oxytocin antagonists [36, 37]. Focal microvibration is characterized by a frequency of 9000 Hz, which is far above the frequency of mechanical stimulation so far investigated for the management of both gait disorders and pain conditions; this peculiar characteristic of Equistasi® limits the understanding of the underlying mechanism of action in the light of current knowledge about the activity of vibrations on pain perception. The effectiveness of the device in the previous studies on gait disorders and the promising results of our work pose the fundamental question if Equistasi® can act through one of the above-mentioned ways or another mechanism of action should be explored; in order to investigate this crucial issue, functional magnetic resonance along with electroencephalography and electroneurography studies could help clarify the brain structures potentially altered by the stimulation and the route through which the microvibration is conveyed.

Our work has some limitations: first, the sample size is small, so our findings might be not applicable to a broader population with different characteristics, and future research on a larger population is fundamental to confirm our results. Second, the positioning of the devices can be difficult for the patients, especially for patients living alone; moreover, the positioning of Equistasi® is strictly operator-dependent and the exact places where the devices have been placed could be forgotten by the patients. The standardization of the positioning is one of the main purposes of our future research in order to reduce physician subjectivity and help patients remember how to apply the device. Another limitation is the follow-up period of 90 days; the stability of our results over time should be assessed by longer studies, as chronic pain is a long-term condition.

Conclusions

In conclusion, focal microvibration administered through Equistasi® is an effective potential tool for the treatment of chronic pain of different origins. As in other non-pharmacological interventions such as neuromodulation techniques, it could help reduce the amount of analgesic drugs with the fundamental advantage of being completely noninvasive. Further research is needed to establish the appropriate indications and to set a standardized positioning of the device according to the characteristics of the pain. In addition, the mechanism through which focal microvibration can modulate pain is so far unexplained, and future studies should address this crucial issue.