The supporting technology (Scrambler Therapy ST5, undergoing trials at Pain Service, Umberto I Hospital, Surgery Department, Frosinone, Italy) was developed as a prototype to allow the required clinical trials to be conducted in order to evaluate the method (Figure 2).
It consists of a multiprocessor apparatus able to simulate five artificial neurons which allow five pain areas in the same person to be treated simultaneously. Application is by means of single-use surface electrodes applied to the skin area corresponding to the pain areas involved. The treatment is fully automated, including the dynamic parametrization required for the correct functioning of the method. This criterion, rendered inevitable by the active principle involved, ensures a very high degree of repeatability of the experimental data as it is not necessary to select the operating parameter manually except for the simple regulation of stimulus intensity, which is manually set at the perception threshold. On the average, each treatment sessions lasts 45 minutes; the required frequency is changed to suit the subject concerned and, after the initial attack therapy, may even consist of a single treatment every 24 hrs.
Eleven patients, (3 males and 8 females; mean age: 63.5 years, range 47-77), all suffering from intense drug-resistant visceral pain and at an advanced stage of oncological disease with widespread metastases, were recruited for the trial.
Inclusion criteria were: presence of very intense visceral pain (baseline visual analogue scale pain value greater or equal to 70) during drug treatment with or without neuropathic complications. Exclusion criteria were: pacemaker user, neurolithic blockage of the celiac plexus and other neurolesive pain control treatments.
Three patients (27.2%) had pancreatic cancer and the remaining 8 patients, although affected by a different type of cancer (4 colon, 4 gastric), displayed intense visceral pain, likely to be associated with neuropathic type complications due to the advancement of the metastatic process. No imaging data are available to support this since it was chosen not to force patients to undergo any further psychological stress and raise their concerns about the advancement of the disease. The life expectancy of all patients was less than two months. In all patients, the failure of all therapeutic approaches other than palliative therapy had also been ascertained.
The trial program was based on a cycle of ten therapy sessions. Each session was performed at the patient's request when the pain reappeared. The timing varied depending on the duration of the state of analgesia in the patient. At the completion of the ten sessions, each patient was allowed to continue the applications until death.
We evaluated the pain intensity before and after each treatment session, the duration of analgesia after treatment and the variation in drug consumption.
Pain intensity was evaluated using the visual analogue scale (VAS) [11, 12]. This linear scale consists of the visual representation of the pain amplitude as perceived by the patient. The amplitude is represented by a 100-mm line long having no reference marks. One extremity indicates absence of pain (0 value) and the other the worst imaginable pain (100 value). The scale was indicated before and after each treatment session by the patient marking the pain level experienced on the scale. This type of test can easily be repeated over time, has the advantage of simplicity, is widely used, is language-independent and is easily understood by the majority of patients.
Each patient was requested to keep a diary in which they noted the duration, expressed in hours, of the absence of pain (or, in the case of partial analgesic effect, from the beginning of the relapse phase) after each treatment, the intensity of the pain when it reappeared and the consumption of painkillers, if used.
The variation in the request for drug treatment is of considerable help in determining whether pain intensity is truly reduced appreciably as indicated by VAS scores. The treatment protocol entailed abandoning or reducing the basic pain control therapy in the case of effective pain reduction by scrambler therapy. Drugs (wherever appropriate) were eliminated in a stepwise fashion during the trial period depending on the molecule used, the baseline dosage and the response to scrambler therapy. A similar criterion was used to reduce the dosage and to vary the type of drug used in order to minimize any undesirable side effects in those cases in which it was not possible to achieve complete elimination. The variation in the request for drug treatment is of considerable help in determining whether pain intensity is truly reduced appreciably as indicated by VAS scores.
Compliance was evaluated through a questionnaire which took into account the degree of satisfaction for the treatment received (as for efficacy and tolerability), any possible adverse effects and the most relevant quality of life parameters (sleep, mood, interrelationships, etc.).
Main Outcome Measures
Remodulation (Raising) of the Pain Threshold
It was evaluated by comparing the pre-treatment VAS data between the first and the tenth treatment session.
Effectiveness within Each Individual Treatment Session
In our specific case, the effects due to the method were assessed by analyzing the pain intensity differences (PID: VAS decrease before and after each treatment). Data referring to the first treatment session is the only one that is not affected by remodulation of the pain threshold and, thus, by the compression of the relative differences in individual responses over the 10 treatment sessions.
The graphic analysis of successive VAS responses and of the percentage ranges of complete or significant pain remission after treatment completes the overall data expression. This was reported by stratifying the severity of pain recorded after treatment as follows: no further pain, VAS equal to 0; slight pain, VAS 1-20; intense pain, VAS greater than 20.
View of Possible Application of the Method at the Patient's Home
An assessment was made of how often treatment would be required to maintain optimal pain control together with the analysis of the persistence of analgesia expressed in hours.
Informed consent was obtained from all the patients recruited. The treatment protocol complied with the 1975 Helsinki guidelines as subsequently amended. The protocol was approved by the Bioethics Committee of the Umberto I Hospital of Frosinone, Italy.
VAS and PID data are reported as mean values and standard deviations (SD). The statistical significance of VAS was measured by means of the paired t-test by running the SPSS/PC+ statistical package using a personal computer. Two-tailed P value less than 0.05 were considered statistically significant.