Motor Cortex Stimulation Provides Long-Term Analgesia for Neuropathic Pain

Epidural motor cortex stimulation (MCS) is an alternative, adjuvant treatment for intractable neuropathic central pain. MCS consists of invasive implantation of a device epidurally with continuous stimulation at frequencies that serve to supplement conventional pharmacologic analgesics. Prior studies have shown that positive analgesic response to noninvasive repetitive transcranial magnetic stimulation (rTMS) serves as an adequate preoperative predictor of continuous MCS efficacy. ^1-3 Therefore, an analgesic effect of noninvasive rTMS often serves as an aid to identify candidates for invasive epidural implantation of the MCS apparatus. However, some studies have shown that a poor rTMS response may fail to identify some successful responders to subsequent MCS.⁴

With this in mind, the authors of “Is Life Better after Motor Cortex Stimulation for Pain Control? Results at Long-Term and their Prediction by Preoperative rTMS,” published in Pain Physician, sought to clarify the predictive value of rTMS with respect to MCS and to assess long-term pain reduction and quality of life scores in a blinded fashion.

For the study, 20 patients (mean age 54.3 years, 45% female), were randomized to two cohorts of sham vs. active 20Hz-rTMS in a cross-over model, before all patientswere submitted to MCS surgery. There was a statistically significant pain reduction of 14.6% for active rTMS versus 2.9% for the sham group. Effects of MCS at six months and six years were included. Fifty percent of patients retained long-term benefit of MCS by both intensity and quality of life assessments (ability to function free of pain and dependence).

The results of this study showed that MCS was beneficial regardless of previous response to non-invasive preliminary rTMS, although positive response to a single session of rTMS by combined pain assessment and henceforth long-term response to continuous MCS had a 90% positive predictive value (PPV) and 67% negative predictive value at long-term assessments.

Transcranial magnetic stimulation was independently efficacious (14.6% vs. 2.9% pain reduction for sham) outside of response to MCS at 6 months and mean 6 years (37% and 28%, respectively). However, those who did experience analgesic effect from rTMS were more likely to benefit from MCS with a 90% PPV.

Commentary from Dr. Mitchell

In this study, assessments of pain improvement were undertaken by blinded physicians, who were naïve to a patient’s cohort designation. Blinded assessments were not done in prior studies with motor cortex stimulation, which may have introduced a form of operator bias into final subjective assessments about pain control. Thus, by the sound methodology of blinded review of a patient’s analgesic response, this study was immune to this form of bias.

The short-term and long-term assessments of pain control and quality of life were included in the longitudinal analysis of transcranial and intracranial stimulation. Though beneficial to survey patients several years after implantation to deduce longevity of analgesia, there would have been some merit to evaluating patients at shorter intervals, such as yearly or every two years to assess the average time to peak efficacy.

The use of both qualitative and quantitative measures of pain relief has more global and clinically-relevant merit than prior studies, which relied on pain score measures. Long-term MCS results on the HowRu questionnaire showed that modulation of anxiety, depression, and vocational/avocational disability measures lagged beyond the noted improvement in physical pain and autonomy. This may be due to recall bias and underestimation of the absolute pain improvement and functioning from a remote point in time.

In addition, the long-term assessment of pain relief carried out over 2-9 years provides a solid basis to determine if pain relief afforded by epidural motor cortex stimulation is fleeting or enduring. Quality of life assessments should be included in future longitudinal studies.

Only 20 patients were studied, and the power of the study is limited. The patient population was not homogeneous, with patients presenting with diverse etiologies of medically refractory neuropathic pain, from central post-stroke pain to trigeminal neuralgia to peripheral brachial plexopathy.

Only three patients experienced interval improvement in pain scores from the 6 months to the mean 6 years assessments. This again may reflect intrinsic differences of this population (concurrent pharmacologic use, central pain etiology more amenable to MCS, concurrent neuroses/psychoses). It would be interesting to explore the neurophysiologic basis of the procedure and explore whether certain pain pathways are more responsive to this modality. For now, this surgical option remains one of adjuvant utility to gold standards of pain management.

Of course, the study was conducted at only one medical center and external validity was reduced, but these results certainly may guide neurologists and neurosurgeons to conduct future higher-powered studies beyond this pilot study, which nevertheless, provides predictive outcomes of this innovative procedure for intractable neuropathic pain.

References:

1. Andre-Obadia N, Mertens P, Lelekov-Boissard T, et al. Is Life Better After Motor Cortex Stimulation for Pain Control? Results at Long-Term and their Prediction by Preoperative rTMS. Pain Physician 2014; 17:53-62.

2. Migita K, Uozumi T, Arita K, Monden S. Transcranial magnetic coil stimulation of motor cortex in patients with central pain. Neurosurg 1995; 36:1037-1039; discussion 1039-1040.

3. Canavero S, Bonicalzi V, Dotta M, et al. Transcranial magnetic cortical stimulation relieves central pain. StereotactFunctNeurosurg 2002; 78:192-196.

4. Lefaucheur JP, Menard-Lefaucheur I, Goujon C, et al. Predictive values of rTMS in the identification of responders to epidural motor cortex stimulation therapy for pain. J Pain 2011; 12:1102-1111.