Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase.
Download Article The Journal of Spinal Cord Medicine, 34(3):285-296, 2011.
Chronic pain is a significant problem for many individuals following spinal cord injury (SCI). Unfortunately, SCI-related neuropathic pain has proven to be largely refractory to analgesic medications and other available treatments. Alpha-Stim cranial electrotherapy stimulation (CES) has been effective in managing some types of pain. It involves the application of a small amount of current through the head via ear clip electrodes. The objective of this study was to explore the effectiveness of CES for neuropathic pain in persons with SCI and chronic pain in a multi-site, double-blind, sham-controlled format conducted at 4 Veterans and one civilian hospital. Adults with SCI and chronic neuropathic pain at or
below the level of injury were randomized to receive active or sham CES 1 hour daily for 21 days. A six-month open-label phase was added to assess ‘as-needed’ CES use.
Assessments were made of changes in pre- to post-session pain ratings as well as change in pain intensity, pain interference, pain quality, pain beliefs and coping strategies, general physical and mental health status, depressive symptomatology, perceived stress, and anxiety.
Of the initial 105 subjects there were 45 subjects in the active group (from a total of 46) and 55 in the sham group (from 59) completing the initial double blind trial. The active group reported a significantly greater average decrease in pain during daily treatments than the sham group (Kruskal–Wallis chi-square = 4.70, P <0.05). During the 21-day trial, there was a significant group × time interaction for only one outcome variable; the active group showed larger pre-to post-treatment decreases in pain interference than the sham group did (F=8.50, P < 0.01, d = 0.59).
In repeated measures ANOVAs, among the eight pre–post pain measures, there were significant main effects of time for six of the eight measures, including BPI Intensity (F=29.66, P<0.001, d=0.40), BPI Interference (F=42.16, P<0.001, d=0.44), SF-36 Pain (F=15.16,
P<0.001, d=0.37), PQAS Paroxysmal Pain (F = 19.88, P < 0.001, d = 0.41), PQAS Deep Pain (F= 9.50, P< 0.01, d=0.22), and Maladaptive Coping (F =18.12, P < 0.001, d= 0.35). There were no significant effects for time on the PQAS Surface Pain and Adaptive Coping scales. BPI Interference (F = 7.37, P< 0.01, d = 0.55), SF-36 Pain (F = 10.35, P < 0.01, d = 0.65), and Maladaptive Coping (F = 6.23, P < 0.05, d = 0.51) showed a significant main effect of group and only BPI Interference showed a significant group × time interaction effect (F = 8.50, P < 0.01, d = 0.59), with the active treatment group showing larger pre- to post treatment decreases in pain interference than the sham group. Because the group × time interaction was significant for BPI Pain Interference, paired t-tests within each group were performed for this measure. Both the active (t = 6.02, P < 0.001, d= 0.73) and sham (t = 2.80, P < 0.01, d = 0.25) groups showed significant improvement in pain interference, but there was less improvement in the sham group.
In the open-label phase of the 55 participants who were assigned to the sham group and who provided post-treatment questionnaire data in the blinded phase, 40 provided questionnaire data following a 3 week open label phase. Paired t-tests were performed to assess change in the pain outcome measures from pre to post-treatment during the open-label phase. The only significant change among the eight pain measures was a significant reduction in BPI Pain Intensity (t =2.08, P < 0.05, d= 0.17).
In the long-term open-label phase for participants who used the device at least once during the 6 months, the total number of days the device was used was significantly inversely correlated to depressive symptomatology (CES-D-10, n = 38,r = −0.41, P < 0.05) and perceived stress (PSS-10, n = 38, r = −0.41, P < 0.05) as measured just prior to the long-term phase. Thus, participants with less depressive symptomatology and less
perceived stress were likely to use the device more often than those with more depressive symptomatology and stress. Frequency of use was not significantly related to demographic characteristics or measures of pain, changes in pain, or health obtained either at study entry or at the beginning of the 6-month phase.
30 participants provided at least some session data in each of the first 3 months of the long-term phase. For these 30 persons, the average before- to after-session decrease in pain was relatively stable (1.37, 1.46, and 1.45 points, respectively, on a 0–10 scale). However, for the 13 persons who
provided at least some session data for all 6 months of the long-term phase, the average session decrease declined over time (1.12, 1.14, 0.94, 0.79, 0.73, and 0.57 points on the 0–10 scale for the decreases in pain during the first through the sixth month of the long-term phase, respectively). 39 participants provided ratings on the BPI at the end of month 3 in the long-term open-label phase: For these average pain intensity decreased from baseline to the end of active CES, either initially or during the 3-week open-label phase, and this decrease was maintained during the first 3 months of the long-term phase. The main effect of time across the 3 time points was significant (F = 5.69, P <
0.01, d = 0.48). There was also a significant linear trend (F = 7.35, P <0.01).
For the 24 persons who also provided BPI data at the end of the sixth month of the long-term phase, the decrease in average pain intensity continued to be maintained. The main effect of time across the 4 data points was significant (F = 10.50, P<0.001, d = 1.31) and there was also a significant linear trend (F = 27.59, P< 0.001).
Participant completed questionnaires regarding their perceptions of CES at 3 (n= 41) and 6 (n = 26) months during the 6-month long-term phase. At 3 months 56% and at 6 months 85% of the respondents who provided satisfaction ratings were somewhat or very satisfied with the device; assuming that the participants who did not provide ratings were not satisfied with the CES device, the overall rates of satisfaction (of all 105 participants) are 22 and 21%, respectively. At 3 months, among those who provided ratings and who were still using the device, 51% reported that the device relieved pain at least a moderate amount, 41% reported that it improved mental health, and 71% said they would continue to
use the device if they could keep it (these percentages are 19, 15, and 26%, respectively, for the participants as a whole, assuming that those not
providing ratings and/or not using the CES device at these times would not find it helpful for reducing pain or improving mental health). Similarly, at 6 months, 54% of the respondents reported at least moderate pain relief, 46% reported at least a moderate improvement in mental health, and 68% said they would continue to use the device if they could keep it (13, 11, and 16% of all 105 participants, respectively). When asked what they liked best about the device, the most common response was that it was easy to use. When asked what they liked least about it, the most common responses were that it did not help the pain and it made the ears tingle or hurt.
BPI average pain intensity across time (3-month assessment in the long-term phase: main effect of time – P < 0.01, linear trend – P <0.01; 6-month assessment in the long term phase: main effect of time – P <0.001, linear trend – P < 0.001).
Individual results varied from no pain relief to a great deal of relief. The researchers concluded that on average, CES appears to have provided a small but statistically significant improvement in pain intensity and pain interference with no serious study-related adverse effects in any phase of the study. The findings indicate that a trial of CES for persons with SCI who have not yet found effective treatment for their neuropathic pain at or below the level of injury may be warranted.
Tan, Gabriel, Rintala, Diana H., Jensen, Mark P., Richards, J. Scott, Holmes, Sally Ann, Parachuri, Rama, Lashgari-Saegh, Shamsi and, Price, Larry R. Efficacy of cranial electrotherapy stimulation for neuropathic pain following spinal cord injury: a multi-site randomized controlled trial with a secondary 6-month open-label phase. The Journal of Spinal Cord Medicine, 34(3):285-296, 2011.
