A pilot study investigating the effects of fast left prefrontal rTMS on chronic neuropathic pain.

OBJECTIVE: Stimulating the human cortex using transcranial magnetic stimulation (TMS) temporarily reduces clinical and experimental pain; however, it is unclear which cortical targets are the most effective. The motor cortex has been a popular target for managing neuropathic pain, while the prefrontal cortex has been investigated for an array of nociceptive pain conditions. It is unclear whether the motor cortex is the only effective cortical target for managing neuropathic pain, and no published studies to date have investigated the effects of prefrontal stimulation on neuropathic pain. DESIGN: This preliminary pilot trial employed a sham-controlled, within-subject, crossover design to evaluate clinical pain as well as laboratory pain thresholds among four patients with chronic neuropathic pain. Each participant underwent three real and three sham 20-minute sessions of 10 Hz left prefrontal repetitive TMS. Daily pain diaries were collected for 3 weeks before and after each treatment phase along with a battery of self-report pain and mood questionnaires. RESULTS: Time-series analysis at the individual patient level indicated that real TMS was associated with significant improvements in average daily pain in 3 of the 4 participants. These effects were independent of changes in mood in two of the participants. At the group level, a decrease of 19% in daily pain on average, pain at its worst, and pain at its least was observed while controlling for changes in mood, activity level and sleep. The effects of real TMS were significantly greater than sham. Real TMS was associated with increases in thermal and mechanical pain thresholds, whereas sham was not. No statistically significant effects were observed across the questionnaire data. CONCLUSIONS: The prefrontal cortex may be an important TMS cortical target for managing certain types of pain, including certain neuropathic pain syndromes.

Fifteen minutes of left prefrontal repetitive transcranial magnetic stimulation acutely increases thermal pain thresholds in healthy adults.

BACKGROUND: Transcranial magnetic stimulation (TMS) of the motor cortex appears to alter pain perception in healthy adults and in patients with chronic neuropathic pain. There is, however, emerging brain imaging evidence that the left prefrontal cortex is involved in pain inhibition in humans. OBJECTIVE: Because the prefrontal cortex may be involved in descending pain inhibitory systems, the present pilot study was conducted to investigate whether stimulation of the left prefrontal cortex via TMS might affect pain perception in healthy adults. METHODS: Twenty healthy adults with no history of depression or chronic pain conditions volunteered to participate in a pilot laboratory study in which thermal pain thresholds were assessed before and after 15 min of repetitive TMS (rTMS) over the left prefrontal cortex (10 Hz, 100% resting motor threshold, 2 s on, 60 s off, 300 pulses total). Subjects were randomly assigned to receive either real or sham rTMS and were blind to condition. RESULTS: Subjects who received real rTMS demonstrated a significant increase in thermal pain thresholds following TMS. Subjects receiving sham TMS experienced no change in pain threshold. CONCLUSIONS: rTMS over the left prefrontal cortex increases thermal pain thresholds in healthy adults. Results from the present study support the idea that the left prefrontal cortex may be a promising TMS cortical target for the management of pain. More research is needed to establish the reliability of these findings, maximize the effect, determine the length of effect and elucidate possible mechanisms of action.

Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study.

BACKGROUND: In a recent preliminary trial in 20 patients after gastric bypass surgery, 20 minutes of repetitive transcranial magnetic stimulation (TMS) over the left prefrontal cortex was associated with a 40% reduction in postoperative patient-controlled morphine use. As is the case with all novel scientific findings, and especially those that might have an impact on clinical practice, replicability is paramount. This study sought to test this finding for replication and to more accurately estimate the effect size of this brief intervention on postoperative morphine use and postoperative pain and mood ratings. METHODS: Twenty participants who underwent gastric bypass surgery completed this replication and extension study. Beck Depression Inventory and Center for Epidemiological Studies Depression scale scores were collected before surgery and at the time of discharge from the hospital. Immediately after surgery, participants were randomly assigned to receive 20 minutes of real or sham repetitive TMS (rTMS) (10 Hz, 10 seconds-ON, 20 seconds-OFF for a total of 4000 pulses). Patient-controlled morphine pump usage was tracked throughout each participant's postoperative hospital stay. In addition, pain and mood ratings were collected via visual analogue scales twice per day. RESULTS: Findings from the original postoperative TMS trial were replicated, as cumulative morphine usage curves were significantly steeper among patients receiving sham TMS, and participants receiving real TMS had used 35% less morphine at the time of discharge than participants receiving sham TMS. At the time of discharge, subjects who had received real TMS had used 42.50 mg of morphine, whereas subjects receiving sham TMS had used an average of 64.88 mg. When the data from the original preliminary trial were combined with the data from this replication trial, a significant difference in cumulative morphine usage was observed between subjects receiving real and sham TMS. Overall, participants who received real TMS used 36% less morphine and had significantly lower ratings of postoperative pain-on-average, and pain-at-its-worst than participants receiving sham. In addition, participants who received real TMS rated their mood-at-its-worst as significantly better than participants receiving sham. The effect of a single 20-minute session of TMS on postoperative pain and morphine use appears to be large (Cohen's d = 0.70) and clinically meaningful. Lastly, cross-lag correlational analyses indicate that improvements in mood follow improvements in pain by approximately 12 hours, supporting the notion that postoperative analgesic TMS effects are not driven by antidepressant effects. CONCLUSIONS: Although more research is needed to verify these observed effects independently, findings from the original postoperative TMS trial were replicated. TMS may have the potential to significantly improve current standards of postoperative care among gastric bypass patients, and further studies may be warranted on other surgical populations. Future investigations should use methodology that permits more definitive conclusions about causal effects of TMS on postoperative pain (for example, double-blinding, sham stimulation that is matched with real TMS with respect to scalp discomfort).