Patient and Public Involvement Statement
Potential participants are identified by healthcare professionals or had contact with the principal investigator of the study. Interested participants are notified of the study and invited to participate in a screening visit.
Eligibility Criteria
Potential participants take part in a screening visit to assess their eligibility. The study is described to the person and any questions are answered. In addition, the potential participant is informed that he/she may withdraw their participation in the study at any time without any consequence. If they decide to participate, they are asked to sign the Informed Consent Form and provided with a copy. The following is the eligibility criteria:
- Participants must be older than 18 years.
- The participant has provided written informed consent to participate.
- The participant must have chronic neuropathic pain due to sensorimotor impairment (for instance PLP).
- At least six months should have passed since the date of injury (to avoid including acute pain).
- If the participant is under pharmacological treatments, there must be no variations in the medication dosages (steady consumption) for at least one-month prior to inclusion.
- If the participant has previously been treated for neuropathic pain, the last session of that/those treatment(s) must be at least three months before inclusion.
- No pain reduction potentially related to previous pain treatments must have been observed for at least three months prior the screening visit, as reported by the participant.
- In the case of having a prosthesis, the participant must be in a stable prosthetic situation (i.e., satisfied with the fitting of the prosthesis).
- Participants must be able to perceive haptic stimulation near the injury or amputation at the time of the screening visit.
- Participants must not experience painful sensations from haptic stimulation (i.e., allodynia).
- The participant has sufficient understanding of Swedish or English to be able to participate in all study assessments.
- Participants should not have any other condition or symptoms that can prevent them from participating to the study, in the researcher’s opinion.
- The participant should not have mental inability, reluctance, or language difficulties that result in difficulty understanding the meaning of study participation.
- The participant should not have any condition associated with risk of poor protocol compliance.
The researcher can at any time terminate the study for a participant due to safety concerns or because the participant does not pursue procedures as planned.
Intervention
The intervention uses two wearable devices: a myoelectric acquisition system with mechanosensory stimulation capabilities [16] (i.e., including actuators for haptic feedback), and a tDCS device for neuromodulation. Excluding the first intervention session, each session is up to three hours comprising of system setup, breaks, and a blinded outcome assessment. A schematic illustration of the setup employed in this clinical investigation used by an elbow disarticulation participant is shown in Figure 1.
Intervention session
Each intervention session, excluding first and last sessions, consist of:
1. Assessment
1a. Pain questionnaire (numeric rating scale)
2. Preparation
2a. Positioning of the participant in a comfortable sitting position for training
2b. Placement of the surface myoelectric electrodes
2c. Positioning of the haptic feedback wearable device
2d. Placement of the brain modulation cap
3. Treatment modalities
Three training modalities are performed during each session. The time dedicated to each modality is equally divided.
3a. Motor training, consisting of:
a. Movement recording session
b. Motor training in Virtual Reality (VR)
c. Motor training by matching random target postures of a virtual arm
d. Serious gaming using visual feedback
3b. Sensory training, consisting of:
a. Haptic feedback discrimination tasks
b. Serious gaming using haptic feedback
3c. Sensorimotor training, consisting of:
- Movements recording session
- Motor training in VR
- Serious gaming using phantom movements, visual, and haptic feedback
Concurrent to performing motor, sensory, and sensorimotor training, the participant receives anodal tDCS over sensorimotor cortex (S1 / M1) with an intensity of 2 mA [10], [11] for 15 minutes at the beginning of each modality.
4. Assessments
4a. Questionnaire for PLP Tracking (Q-PLPT); described in the Outcomes section
Level of difficulty of the training modalities
The level of difficulty is gradually increased by the therapist (i.e., an instructed researcher) during the treatment period to challenge the participant according to their capability. The consistent challenge to fully focus on motor control and/or sensory perception is why the therapy is deemed as “mindful”. The level of difficulty is gradually increased as follows:
a) Motor training
The level of difficulty is increased by increasing the number of degrees of freedom. The participant starts the training with one degree of freedom, then multiple degrees, and later advances to simultaneous movements involving at least two degrees of freedom.
b) Sensory training
Level of difficulty is increased using different actuators for haptic feedback and mixing different perceptions, directions, and moving from gross to fine perception tasks.
c) Sensorimotor training
Level of difficulty is increased through a combination of motor and sensory difficulty levels. The therapist increases the level of difficulty gradually and returns to the previous level if the participant cannot achieve the new tasks.
Outcomes
Following the schedule presented in Table 2, the therapist (T) conducts the interventions, and the evaluator (E) registers the outcomes.
Table 2 Summary of the different actions occurring in different visits. T = Therapist, E = Evaluator.
Session
|
Actions occurring in different visits
|
Screening visit
|
- Medical history (T)
- Study Consent (T)
|
Baseline assessments
|
- Questionnaires: Q-PLPT, EQ-5D-5L, PDI, PSEQ-2, PCS-06, PHQ-2, Expect-SF (E)
- Brain imaging assessments: fMRI and EEG (T)
|
Intervention visit 1
|
- Intervention (T)
- Functional Assessments (E)
- Questionnaires: NRS, Q-PLPT, OAT (E)
- Brain imaging assessment: EEG (T)
|
Intervention visits 2 to visit 14
|
- Intervention (T)
- Functional Assessments (E)
- · Questionnaires: NRS, Q-PLPT (E)
- Imaging assessment: EEG (T)
|
Intervention visit 15
|
- Intervention (T)
- Functional Assessments (E)
- Questionnaires: NRS, Q-PLPT, PDI, EQ5D-5L, PSEQ-2, PCS-SF, PHQ-2 (E)
- Imaging assessment: EEG (T)
|
Post treatment assessments
|
- Functional Assessments (E)
- Questionnaires: NRS, Q-PLPT, PDI, EQ5D-5L, PSEQ-2, PCS-SF, PHQ-2 (E)
- Imaging assessments: fMRI and EEG (T/E)
|
Follow-ups, at 1, 3, and 6 months after the last intervention
|
- Functional Assessments (E)
- Questionnaires: NRS, Q-PLPT, PDI, EQ5D-5L, PSEQ-2, PCS-SF, PHQ-2 (E)
|
Primary outcome: Pain Rating Index (PRI)
The primary outcome, PRI measures the changes in PLP before and after treatment and is calculated as sum of the values for all the descriptors of the Short Form of the McGill Pain Questionnaire. In this study, the PRI is included in the Questionnaire for PLP Tracking (Q-PLPT), described later in this section.
Secondary outcome: Pain Disability Index (PDI)
PDI consists of seven items measuring the aspects of life affected by pain [15]. PDI value is computed by sum of the values of all items.
In addition to the primary and secondary outcomes, the study also includes the following outcomes:
Participant’s medical history
The medical history is collected to determine factors related to PLP and its etiology. This information includes type and time of amputation, previous treatments for pain, medications, and comorbidities.
Numeric Rating Scale (NRS)
This is a one item questionnaire scaled from zero to ten to measure the pain every intervention.
Questionnaire for PLP Tracking (Q-PLPT)
Questionnaire based on the short version of the McGill Pain Questionnaire (SF-MPQ) [17] to investigate components of PLP. Q-PLPT also includes specific questions that have been modified to fit the study population, as well as additional relevant questions. Taken together, the Q-PLPT includes questions addressing the intensity, quality, duration, and frequency of pain, as well as intrusion of pain in sleep, and how the participant perceives pain [14], [18]–[20].
EuroQoL-5D-5L (EQ-5D-5L)
Questionnaire to measure health-related quality of life by evaluating the health conditions[21]. Health conditions regards to five-items of mobility, self-care, usual activities, pain/discomfort, and anxiety/depression where each item is scored from zero to five. Health evaluation section of the questionnaire measures the best health condition that the participant can imagine on scale of hundred with zero as the worst and hundred as the best.
Pain Self-Efficacy Questionnaire (PSEQ-2)
PSEQ-2 is a survey with two questions to measure self-efficacy regarding ability to perform activities in individuals with chronic pain, on a scale from zero to six [22].
Pain Catastrophizing scale-6 (PCS-6)
Six-item questionnaire to measure catastrophizing thinking on a scale from zero to four [23], [24].
Patient Health Questionnaire-2 (PHQ-2)
Two-item questionnaire to assess the existence of a depressed mood and loss of interest in daily activities [25]. Each item is scored from zero to three.
Patients' Global Impression of Change (PGIC) scale
One-item questionnaire assessed after receiving the treatment to measure the participant’s belief about the efficacy of the treatment, on a scale from zero to seven [26].
Short Form of the EXPECT Questionnaire (EXPECT-SF)
Questionnaire to evaluate the effects that the treatment may have on the participant’s pain and how the pain might impact their life. Each question relates to the expected results at the end of the treatment period.
Opinion About Treatment (OAT)
Three-item questionnaire regards to the participant’s opinion about the treatment.
Imaging assessments
Non-invasive brain imaging assessments such as functional Magnetic Resonance Imaging (fMRI) and Electroencephalography (EEG) are performed to conduct further exploratory studies on neural correlates of pain.
Functional assessments
Functional assessments are performed to investigate changes in sensory and motor function before and after our intervention:
- Sensory acuity. The Semmes-Weinstein monofilament test and the two-point discrimination test [27], [28] are used to assess tactile sensitivity by measuring the ability to discriminate pressure at a single point of contact, and the minimal distance between two points of contact, respectively.
- Affected and Intact Limb Movement. Affected limb movement is assessed by executing movements at different joints and/or parts of the affected limb depending on the level of amputation or the injured nerves. In case of amputation, participants are asked to imitate movements by their intact limb. The changes in the range of motion pre- and post- treatment are measured by using an adapted motion capture system for upper limb and a goniometer for lower limb.
Semi-structured qualitative interviews
Participants are asked to participate in brief, semi-structured interviews that aim to more deeply understand how they have experienced the treatment and how it has affected their quality of life in general. Interviews are recorded and transcribed, then coded and categorized into themes for analysis, as described by Malterud [29]. Interviews will be performed in Swedish or English and, if necessary, translated into English for analysis.
Sample size
The sample size was calculated based on the result of the primary outcome, comparing PRI, of the study on PME for treatment of PLP in a previous study [6]. Eight participants were deemed necessary for a power of 80% and an alpha value of 5%. No dropouts are expected. In the case that participants miss a visit or an assessment, missing values will not be included in statistical analyses.