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Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients.

Tzabazis A, Aparici CM, Rowbotham MC, Schneider MB, Etkin A, Yeomans DC - Mol Pain (2013)

Bottom Line: The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability.A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers.In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients.

Methods: Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H2(15)O positron emission tomography - computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRS(TMS)-NRS(placebo)) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded.

Results: A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session.

Conclusion: Multi-coil rTMS may be a safe and effective treatment option for acute as well as for chronic pain, such as that accompanying fibromyalgia. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments.

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Three coil configurations used in the PET imaging study are displayed over standard EEG10-20 coil positions. Large circles represent the coils, and the arrows within represent the direction of the primary electrical current within that coil at the point of contact with the scalp. Note that all configurations have the same four geometric centers for each coil, but the coils are variously rotated so as to shape the magnitude and direction of the resulting magnetic field. The diagram is a planar representation of the curved head surface such that F3, F4 (lateral) and Fpz (anterior) positions are actually approximately vertical and at 90 degrees from the most posterior (“top” coil).
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Figure 4: Three coil configurations used in the PET imaging study are displayed over standard EEG10-20 coil positions. Large circles represent the coils, and the arrows within represent the direction of the primary electrical current within that coil at the point of contact with the scalp. Note that all configurations have the same four geometric centers for each coil, but the coils are variously rotated so as to shape the magnitude and direction of the resulting magnetic field. The diagram is a planar representation of the curved head surface such that F3, F4 (lateral) and Fpz (anterior) positions are actually approximately vertical and at 90 degrees from the most posterior (“top” coil).

Mentions: The 1 Hz pulse frequency that showed analgesic effect in the acute pain/volunteer study was not effective for the treatment of chronic pain in fibromyalgia patients. This might be explained by a relatively short-termed effect induced by this stimulation frequency. In volunteers, the acute analgesic effect appeared to last only about 6 minutes on average (Figure 4). The hyperalgesic effect observed after TMS with configuration C showed a similar decrease over time. Those effects are most likely not due to habituation, since similar trends were not observed for configuration A. Another factor that may explain the lack of effect of the 1Hz setting in the fibromyalgia patient population is the difference in age of subjects. In fact, the oldest volunteer was younger than the youngest fibromyalgia patient. Specific configurations might be necessary to obtain desired changes in brain plasticity depending on the age of treated subjects. Future studies should be performed to evaluate effects of age-specific rTMS configurations. A final explanation might be related to morphometric, and presumably cytoarchitectonic structural differences between the dACC of normal volunteers and those of fibromyalgia patients [12]. It may be that the smaller restructured dACC of fibromyalgia patients may be inherently less susceptible to low frequency pulses. Perhaps the most significant finding from these studies is the persistence of analgesic effects for at least 4 weeks after the final treatment session. This effect implies that multiple sessions of rTMS may be inducing neuroplastic processes. It will be critical, in future studies, to determine whether and to what extent these events are recognizable in structural and/or functional scans of similarly treated patients, e.g. reversal of the previously observed morphological differences in the dACC of fibromyalgia patients.


Shaped magnetic field pulses by multi-coil repetitive transcranial magnetic stimulation (rTMS) differentially modulate anterior cingulate cortex responses and pain in volunteers and fibromyalgia patients.

Tzabazis A, Aparici CM, Rowbotham MC, Schneider MB, Etkin A, Yeomans DC - Mol Pain (2013)

Three coil configurations used in the PET imaging study are displayed over standard EEG10-20 coil positions. Large circles represent the coils, and the arrows within represent the direction of the primary electrical current within that coil at the point of contact with the scalp. Note that all configurations have the same four geometric centers for each coil, but the coils are variously rotated so as to shape the magnitude and direction of the resulting magnetic field. The diagram is a planar representation of the curved head surface such that F3, F4 (lateral) and Fpz (anterior) positions are actually approximately vertical and at 90 degrees from the most posterior (“top” coil).
© Copyright Policy - open-access
Related In: Results  -  Collection

License
Show All Figures
getmorefigures.php?uid=PMC3750766&req=5

Figure 4: Three coil configurations used in the PET imaging study are displayed over standard EEG10-20 coil positions. Large circles represent the coils, and the arrows within represent the direction of the primary electrical current within that coil at the point of contact with the scalp. Note that all configurations have the same four geometric centers for each coil, but the coils are variously rotated so as to shape the magnitude and direction of the resulting magnetic field. The diagram is a planar representation of the curved head surface such that F3, F4 (lateral) and Fpz (anterior) positions are actually approximately vertical and at 90 degrees from the most posterior (“top” coil).
Mentions: The 1 Hz pulse frequency that showed analgesic effect in the acute pain/volunteer study was not effective for the treatment of chronic pain in fibromyalgia patients. This might be explained by a relatively short-termed effect induced by this stimulation frequency. In volunteers, the acute analgesic effect appeared to last only about 6 minutes on average (Figure 4). The hyperalgesic effect observed after TMS with configuration C showed a similar decrease over time. Those effects are most likely not due to habituation, since similar trends were not observed for configuration A. Another factor that may explain the lack of effect of the 1Hz setting in the fibromyalgia patient population is the difference in age of subjects. In fact, the oldest volunteer was younger than the youngest fibromyalgia patient. Specific configurations might be necessary to obtain desired changes in brain plasticity depending on the age of treated subjects. Future studies should be performed to evaluate effects of age-specific rTMS configurations. A final explanation might be related to morphometric, and presumably cytoarchitectonic structural differences between the dACC of normal volunteers and those of fibromyalgia patients [12]. It may be that the smaller restructured dACC of fibromyalgia patients may be inherently less susceptible to low frequency pulses. Perhaps the most significant finding from these studies is the persistence of analgesic effects for at least 4 weeks after the final treatment session. This effect implies that multiple sessions of rTMS may be inducing neuroplastic processes. It will be critical, in future studies, to determine whether and to what extent these events are recognizable in structural and/or functional scans of similarly treated patients, e.g. reversal of the previously observed morphological differences in the dACC of fibromyalgia patients.

Bottom Line: The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability.A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers.In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz.

View Article: PubMed Central - HTML - PubMed

ABSTRACT

Background: Repetitive transcranial magnetic stimulation (rTMS) has shown promise in the alleviation of acute and chronic pain by altering the activity of cortical areas involved in pain sensation. However, current single-coil rTMS technology only allows for effects in surface cortical structures. The ability to affect activity in certain deep brain structures may however, allow for a better efficacy, safety, and tolerability. This study used PET imaging to determine whether a novel multi-coil rTMS would allow for preferential targeting of the dorsal anterior cingulate cortex (dACC), an area always activated with pain, and to provide preliminary evidence as to whether this targeted approach would allow for efficacious, safe, and tolerable analgesia both in a volunteer/acute pain model as well as in fibromyalgia chronic pain patients.

Methods: Part 1: Different coil configurations were tested in a placebo-controlled crossover design in volunteers (N = 16). Tonic pain was induced using a capsaicin/thermal pain model and functional brain imaging was performed by means of H2(15)O positron emission tomography - computed tomography (PET/CT) scans. Differences in NRS pain ratings between TMS and sham treatment (NRS(TMS)-NRS(placebo)) which were recorded each minute during the 10 minute PET scans. Part 2: 16 fibromyalgia patients were subjected to 20 multi-coil rTMS treatments over 4 weeks and effects on standard pain scales (Brief Pain Inventory, item 5, i.e. average pain NRS over the last 24 hours) were recorded.

Results: A single 30 minute session using one of 3 tested rTMS coil configurations operated at 1 Hz consistently produced robust reduction (mean 70% on NRS scale) in evoked pain in volunteers. In fibromyalgia patients, the 20 rTMS sessions also produced a significant pain inhibition (43% reduction in NRS pain over last 24 hours), but only when operated at 10 Hz. This degree of pain control was maintained for at least 4 weeks after the final session.

Conclusion: Multi-coil rTMS may be a safe and effective treatment option for acute as well as for chronic pain, such as that accompanying fibromyalgia. Further studies are necessary to optimize configurations and settings as well as to elucidate the mechanisms that lead to the long-lasting pain control produced by these treatments.

Show MeSH
Related in: MedlinePlus