Transcranial Magnetic Stimulation-Mediated Analgesia is Independent of Improvements in Depression

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Repetitive transcranial magnetic stimulation of the right secondary somatosensory motor cortex produces relief from chronic neuropathic orofacial pain.
Repetitive transcranial magnetic stimulation of the right secondary somatosensory motor cortex produces relief from chronic neuropathic orofacial pain.

Repetitive transcranial magnetic stimulation of the right secondary somatosensory motor cortex (S2) produces pain relief in patients with chronic neuropathic orofacial pain, an effect that was shown to be direct, and not a result of improvements in psychiatric or sleep disorder comorbidities. These findings were published in November in Medicine.1

A previous study by the same group reported that high-frequency rTMS stimulation of S2 had analgesic effects, as indicated by lower pain score on the NRS reported by patients subjected to S2 vs sham stimulation (=.0071).2

In the current study, the researchers at Turku University Hospital in Finland assessed the effects of rTMS on sleep and psychiatric disorders that are common neuropathic pain comorbidities, as well as the influence of these comorbidities on rTMS-associated analgesia, by examining the effects of repetitive transcranial magnetic stimulation (rTMS) in 16 patients (ages 37-74; mean age 59) from 2009 to 2011 who presented with drug-resistant orofacial neuropathic pain.

The study participants had been diagnosed by a neurologist and an orofacial pain physician as follows: 7 had trigeminal neuropathic pain, 4 had atypical facial pain, and 5 had burning mouth syndrome. All patients displayed dysfunction of the trigeminal small- (and also large-, in some) fiber system, as well as a score ≥4 on the 0 to 10 numerical rating scale (NRS) for chronic daily neuropathic orofacial pain (daily average, 5.7; mean duration, 10.4 years).

Each study participant received 3 rTMS treatments (one of which was a placebo session), administered 4 weeks apart in a single-blind/within-subject manner. Stimulations (50 pulses at 90% of the resting motor threshold, every 10 s) targeted the facial area within the somatotopic representation of the primary sensorimotor cortex (S1/M1) and S2 in a random order.

Patients were assessed for psychiatric disorders based on the structured clinical interview for axis I disorders.3 Pain, mood, sleep and quality of life were assessed by study participants using the NRS to rate both pain and sleep and collected in study diaries for 4 weeks prior to and following treatment.

In addition, total hours of sleep, intensity, and interference of pain (measured using the Brief Pain Inventory),4 and sleep characteristics (assessed using the Basic Nordic Sleep Questionnaire),5 were all reported.

A more thorough assessment of sleep quality, measuring the 6 dimensions of sleep (ie, sleep disturbance , snoring, awakening with shortness of breath or headache, sleep adequacy, daytime somnolence, and quantity of sleep) was achieved through the Medical Outcomes Study (MOS) Sleep Measure, prior to and 1 month following each rTMS session.6

The authors found that neither sleep nor psychiatric disorders or medications (eg, opioids) had predictive value for rTMS treatment efficacy in study participants. The treatments had no detectable impact on either mood (assessed with the Beck Depression Inventory),7 or sleep quality.

Pain scores specific to neuropathic pain — but not to general pain — were reduced following S2 stimulation, as indicated by lower scores on the Neuropathic Pain Impact on Quality-of-Life questionnaire8 in treated vs sham-stimulated patients (P=.0031).

Six (38%) and 10 (63%) of the patients had a current or lifetime psychiatric disorder (depression or anxiety), respectively.

The authors concluded that “the present results show that the analgesic effect of rTMS given to the right S2 cortex as previously reported is most likely due to a direct action on specific top-down pain modulation networks rather than a result of an indirect action via improvement of comorbid psychiatric or sleep disturbances.”

They also added that “S2 stimulation had no effect on depressive symptoms, sleep diary measures, or the MOS sleep scale index scores, and that “comorbidities such as depression, anxiety disorders, and sleep problems did not predict the rTMS treatment outcome.”

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References

  1. Lindholm P, Lamusuo S, Taiminen T, et al. The analgesic effect of therapeutic rTMS is not mediated or predicted by comorbid psychiatric or sleep disorders. Medicine (Baltimore). 2016;95(44):e5231. doi: 10.1097/MD.0000000000005231.
  2. Lindholm P, Lamusuo S, Taiminen T, et al. Right secondary somatosensory cortex-a promising novel target for the treatment of drug-resistant neuropathic orofacial pain with repetitive transcranial magnetic stimulation. Pain. 2015;156(7):1276-1283.
  3. First MB, Spritzer RL, Gibbon M, et al. Structured clinical interview for DSM-IVaxis I disorders (SCID-I, 4/97 version). NewYork, NY: Biometrics Research Department, New York State Psychiatric Institute; 1997.
  4. Cleeland CS, Ryan KM. Pain assessment: global use of the Brief Pain Inventory. Ann Acad Med Singap. 1994;23(2):129-138.
  5. Partinen M, Gislason T. Basic Nordic Sleep Questionnaire (BNSQ): a quantitated measure of subjective sleep complaints. J Sleep Res. 1995;4:150–155.
  6. Spritzer KL, Hays RD. MOS sleep scale: a manual for use and scoring, Version 1.0. Los Angeles, CA:2003, November.
  7. Beck AT, Rial WY, Rickels K. Short form of depression inventory: crossvalidation. Psychol Rep. 1974;34:1184–1186.
  8. Poole HM, Murphy P, Nurmikko TJ. Development and preliminary validation of the NePIQoL: a quality-of-life measure for neuropathic pain. J Pain Symptom Manage. 2009;37:233–245.


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