Table of Contents  
ORIGINAL ARTICLE
Year : 2012  |  Volume : 6  |  Issue : 1  |  Page : 7-10

Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces post-thoracotomy pain


1 Department of Anesthesiology, Faculty of Medicine, Cairo University, Giza, Egypt
2 Department of Medicine, The University of Melbourne, Melbourne, Victoria, Australia

Date of Submission15-Feb-2012
Date of Acceptance01-Apr-2012
Date of Web Publication30-Jun-2014

Correspondence Address:
Mohamed Bakry
MD, Department of Anaesthesiology, Faculty of Medicine, Cairo University, 12111 Giza
Egypt
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Source of Support: None, Conflict of Interest: None


DOI: 10.7123/01.EJCA.0000415931.14020.c8

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  Abstract 

Objective

Several recent studies have suggested that repetitive transcranial magnetic stimulation (rTMS) can temporarily reduce the need for analgesia postoperatively. We aimed to determine the effects of prefrontal cortex stimulation using TMS on post-thoracotomy pain.

Methods

Twenty patients who had undergone thoracic surgery were studied. Immediately after surgery, the patients were randomly assigned to receive 20 min of active or sham rTMS (10 Hz, 10-s ON, and 20-s OFF for a total of 4000 pulses). Participants rated pain and mood twice per day using visual analog scale.

Results

Groups were similar at baseline in terms of the BMI, age, mood ratings, pain ratings, surgery duration, time under anesthesia, and surgical anesthesia methods. Active prefrontal rTMS was associated with a 40% reduction in total morphine use compared with sham during the 48 h after surgery. Participants who received active rTMS also reported significantly lower ratings of postoperative pain-on-average and pain-at-its-worst than participants receiving sham.

Conclusion

A single session of postoperative prefrontal rTMS was associated with a reduction in post-thoracotomy pain. This is clinically important because it offers the potential of reducing the need for the postoperative use of analgesia such as morphine. These analgesics are associated with complications (e.g. respiratory depression), especially in patients undergoing thoracotomy for chest diseases.

Keywords: lobectomy, PCA, post-thoracotomy pain, transcranial magnetic stimulation


How to cite this article:
Bakry M, Bakry R. Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces post-thoracotomy pain. Egypt J Cardiothorac Anesth 2012;6:7-10

How to cite this URL:
Bakry M, Bakry R. Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces post-thoracotomy pain. Egypt J Cardiothorac Anesth [serial online] 2012 [cited 2019 Nov 12];6:7-10. Available from: http://www.ejca.eg.net/text.asp?2012/6/1/7/135558


  Introduction Top


Several recent studies have shown analgesic effects associated with the stimulation of the prefrontal cortex through transcranial magnetic stimulation (TMS). One study reported a significant reduction in reported pain experience in a single patient with chronic facial pain following fast repetitive TMS (rTMS) (20 Hz) at 100% of resting motor threshold over the left prefrontal cortex 1. In another large-scale study, slow rTMS (1 Hz) of the right prefrontal cortex was associated with significant antinociceptive effects over and above other cortical targets (e.g. left and right motor cortex and vertex) in healthy adults 2. Slow TMS over the right prefrontal cortex was also associated with significant pain relief in patients with fibromyalgia 3. In addition, 10 Hz TMS over the left prefrontal cortex significantly reduced pain perception in patients with major depression, an effect that could not be explained by the antidepressant effects of the TMS 4.

The majority of studies on the effects of rTMS on pain perception suggest short-lived pain-modulation effects. Thus, it has been suggested that currently, clinical rTMS applications may be limited to repeated use for controlling neuropathic pain syndromes for a short period, perhaps while a patient is waiting for surgical implantation of motor cortex stimulation systems 5,6. However, little attention has been paid to the potential effect of rTMS on acute postoperative pain. This is an important area of research to consider. If an appropriately timed, brief, relatively noninvasive intervention can significantly reduce acute postsurgical pain and consequent opioid use, standard interventions for postsurgical pain management could be significantly enhanced.

This was shown recently in two studies, in which 20 min of fast rTMS over the left prefrontal cortex was associated with a reduction in postoperative patient-controlled analgesia use in gastric bypass surgery patients 7,8. These findings are especially significant, given the negative respiratory side effects of pain and opioid treatment and the high proportion of obese patients with apnea and other respiratory problems.

The aim of the current study is to determine the effect of rTMS of the prefrontal cortex in patients with acute post-thoracotomy pain and its efficacy in pain reduction.


  Methods Top


Participants

Ethics approval from the hospital’s ethics committee was obtained before commencing the study, and verbal and written informed consent was obtained from the participants before commencing TMS stimulation.

Twenty-two adult patients, men and women, all of whom had undergone thoracic surgery (for lobectomy) through a lateral thoracotomy incision between April 2010 and May 2011 were enrolled in this study. Two participants were excluded because the motor threshold was higher than the maximum intensity of the TMS machine.

Inclusion criteria: (a) thoracic surgery for lobectomy and (b) pulmonary functions above 50% of the predicted (FEV1/FVC>50% predicted, FEV1>2 l, predicted postoperative FEV1>40% of the predicted).

Exclusion criteria: (a) previous brain surgery (b) use of pacemakers or vagal nerve stimulators, (c) profound motor weakness, (d) mechanical ventilation, (e) intellectually disabled.

Using a computer-generated list, patients were randomly allocated to one of two groups. Patients in the rTMS group received one session of active left prefrontal TMS postoperatively, whereas patients in the sTMS group served as controls.

Anesthesia protocol

The same anesthetic technique was used in patients using the same anesthetic and analgesic drugs as follows:

  1. Patients were monitored using a five-lead ECG with simultaneous monitoring of lead II and V, pulse oximeter, end tidal CO2 and invasive arterial blood pressure measurements, and a central venous line. (A triple-lumen catheter was inserted into the jugular vein on the side of surgery for the purpose of central venous pressure monitoring and infusion of drugs using the internal jugular anterior approach.)
  2. Induction and maintenance protocol consisted of administration of propofol 1% 2 mg/kg, fentenyl 2–3 mcg/kg, attracuriam besylate 0.4–0.5 mg/kg, morphine IV 0.05–0.1 mg/kg, isoflurane (inspired concentration 1–1.5%), and mechanical ventilation (tidal volume 5–6 ml/kg, respiratory rate 12/min), followed by an intercostal nerve block using lidocaine (20 cc 1% solution with adrenaline 1 : 200 000, the block was performed at the level of the incision and at 2 levels above and below it) performed at the end of surgery under direct vision by the surgeon before closure of the thorax.
  3. Recovery included reversal (neostigmine 0.03–0.08 mg/kg and glycopyrrolate 0.2–0.4 mg) and extubation.
  4. Postoperative therapy included the administration of patient-controlled analgesia using morphine [2 mg boluses with a lockout period of 20 min and a maximum dose of 4 mg/h to avoid patient sedation or drowsiness, which may affect the patient’s ability to report pain and mood using visual analog scale (VAS)]. Adjuvant therapy including ketorolac 30 mg IV was also administered mainly after the first day of surgery.


Transcranial magnetic stimulation

After surgery, patients were transferred to the post anesthesia care unit for observation and, on fulfilling the criteria of discharge (achieving a score of 9 or more using the modified Aldrete scale), they were transferred back to the ward, where each participant underwent a motor threshold assessment (which was explained to all patients as part of the informed consent preoperatively); patients requiring intensive care stay (three patients) underwent TMS in the ICU. For this, a figure-of-eight stimulating coil was held over the optimal scalp site (motor cortex) for inducing responses in the abductor pollicis brevis muscle, with the handle pointing posteroanterior. Surface electromyographic recording was performed from the abductor pollicis brevis muscle. Stimulation commenced at 30% of the maximum output and increased in 5% increments until the motor-evoked potential was established. One percent changes in intensity were then used to measure the threshold value. Motor threshold was defined as the lowest level of stimulus intensity that produced a motor-evoked potential in the target muscle of peak-to-peak amplitude above 100 μV on 50% or more of 10 trials 9.

Participants’ prefrontal cortices were then located according to convention by moving the coil 5 cm anterior from the area of the motor cortex associated with thumb movement along the parasagittal line.

Participants were then randomly assigned to receive active TMS (n=10) or sham TMS (n=10). The active TMS coil is a figure eight design with a solid core interior (Neuronetics Inc., Malvern, Pennsylvania, USA). The sham coil is externally identical to the active TMS coil, except that no cortical stimulation occurs as a hidden aluminum insert on the surface next to the scalp blocks passage of the magnetic field. Participants received 20 min of 10 Hz rTMS at 100% of rMT (10-s stimulation trains with 20-s interstimulus intervals) for a total of 4000 pulses.

Participants provided VAS ratings of pain (on average, at its worst, and at its least) and visual analog mood scale ratings of mood (on average, at its worst, and at its best) twice per day while lying in bed. This was collected by nurses starting from day one after surgery. Postoperative usage of analgesia was monitored and recorded. Participants, medical staff providing clinical care to participants, and nurses collecting ratings were blinded to whether participants had received active or sham TMS. The only individual who was aware of the randomization was the TMS administrator, who was not aware of the surgical history and medication loading. The administrator followed a careful script with patients, physicians, and nurses, and had no contact with any of the patients after the TMS session (i.e. during the period when participants were using their analgesia and providing ratings of pain and mood).

The primary efficacy measure was the effect of left prefrontal TMS on acute post-thoracotomy pain; the secondary measures were its effect on mood and the total morphine consumption in patients.

Statistical analysis

The primary efficacy end point was defined prospectively as a reduction in pain using the VAS (0 no pain–10 worst pain), with the assumption of a difference of 3 points in the VAS and 2 SD with a type 1 error of 0.05, and to achieve 80% power of study, the required sample size is a minimum of nine patients in each group.

The demographic data (age, BMI) and duration of surgery and intraoperative drug dosages were compared using the one-way analysis of variance (ANOVA) test. A multivariant ANOVA (MANOVA) (TMS condition; active vs. sham) model was used, controlling for pre-TMS pain and mood ratings on the total morphine used at the time of discharge. The mean pain VAS and mood VAS ratings were averaged across time and a MANOVA was carried out to evaluate differences in the ratings between groups. All statistical calculations were performed using computer programs Microsoft Excel version 2010 (Microsoft Corporation, New York, New York, USA) and statistical package for social science (SPSS Inc., Chicago, Illinois, USA) version 15 for Microsoft windows.


  Results Top


No baseline differences were found between the active and the sham TMS groups in terms of age, BMI, fentanyl consumption, pre-TMS morphine bolus, ketorolac, lidocaine, preoperative pain ratings, preoperative mood ratings, pre-TMS pain ratings, pre-TMS mood ratings, or duration of surgery [Table 1].
Table 1: Patient and operative characteristics and pre-transcranial magnetic stimulation variables in the present study

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Participants who received active TMS used an average of 43 mg (SD=20) of morphine and participants who received sham TMS used 70 mg (SD=42). Active TMS was associated with a 40% decrease in the total morphine usage at the time of discharge. A significant main effect was found [F(2, 49)=P<0.05].

Participants who received active TMS reported lower ratings of pain-on-average, pain-at-its-worst, and reported better mood ratings when pain was at its worst than did participants receiving sham TMS. There was a significant effect for TMS condition [sham vs. active; F(5, 91)=P<0.05] on the pain VAS and mood VAS scales [Figure 1].
Figure 1: Mean pain VAS and mood VAS ratings of the participants receiving active (n=10) or sham (n=10) TMS post-thoracic surgery (*P<0.05). Higher ratings indicate better mood. TMS, transcranial magnetic stimulation; VAS, visual analog scale.

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Participants who received active TMS experienced improvements in mood ∼10 h after the decrease in pain.


  Discussion Top


In the present study, we report that a single 20-min postoperative prefrontal rTMS session in thoracic surgery patients may significantly reduce post-thoracotomy pain and postoperative morphine usage. The results show that active TMS was associated with an overall 40% reduction in morphine usage. In addition, participants who received active TMS rated their postoperative pain-on-average and pain-at-its-worst significantly lower than participants who received sham TMS, despite having less morphine in their systems. Participants receiving active TMS rated their mood-at-its worst as better than participants receiving sham. Furthermore, improvements in mood followed improvements in pain by ~10 h, supporting the notion that postoperative analgesic TMS effects are not driven by antidepressant effects.

Participants’ prefrontal cortices were located according to convention by moving the coil 5 cm anterior from the area of the motor cortex associated with thumb movement along the parasagittal line. Although more sophisticated image-guided systems are available for locating specific cortical areas, we chose this approach because: (a) we did not have an image-guided system, (b) TMS image-guided systems require structural MRI scans that are costly to acquire, and (c) we aimed to evaluate the effects of TMS using methods that are easy for others to replicate.

The mechanisms by which prefrontal rTMS may modulate pain experience are unclear. However, previous research suggests that prefrontal rTMS may lead to inhibition of limbic activity associated with both pain and depressed mood 10, and there is evidence to support the concept that left prefrontal activation is negatively correlated with pain unpleasantness 11. In addition, prefrontal activation has also been linked to pain catastrophizing 12 and this idea was supported by our findings that participants receiving active TMS had significantly lower pain-at-its-worst and significantly better mood-at-its-worst ratings than participants receiving sham TMS.

Although the results of the current study as well as the previous studies are very promising, much still remains to be verified. It is not clear whether the prefrontal cortex is the only (or even the best) cortical target for modulating postoperative pain. The optimal device parameters (TMS intensity, frequency, and number of pulses) for managing pain are also not clear. Further investigations to confirm whether TMS may be used to modulate pain experience during critical periods, to alter the course of acute pain and the consequent trajectory of opioid usage, are thus important. TMS may have the potential to significantly improve the current standards of postoperative care not only among thoracic surgery patients but also many other surgical populations.[12]

 
  References Top

1.Reid P, Pridmore S. Improvement in chronic pain with transcranial magnetic stimulation. Aust N Z J Psychiatry. 2001;35:252  Back to cited text no. 1
    
2.Graff Guerrero A, González Olvera J, Fresán A, Gómez Martín D, Méndez Núñez JC, Pellicer F. Repetitive transcranial magnetic stimulation of dorsolateral prefrontal cortex increases tolerance to human experimental pain. Cogn Brain Res. 2005;25:153–160  Back to cited text no. 2
    
3.Sampson SM, Rome JD, Rummans TA. Slow-frequency rTMS reduces fibromyalgia pain. Pain Med. 2006;7:115–118  Back to cited text no. 3
    
4.Avery DH, Holtzheimer PE III, Fawaz W, Russo J, Neumaier J, Dunner DL, et al. Transcranial magnetic stimulation reduces pain in patients with major depression: a sham-controlled study. J Nerv Ment Dis. 2007;195:378–381  Back to cited text no. 4
    
5.Lefaucheur JP. New insights into the therapeutic potential of non-invasive transcranial cortical stimulation in chronic neuropathic pain. Pain. 2006;122:11–13  Back to cited text no. 5
    
6.Lefaucheur JP, Drouot X, Ménard Lefaucheur I, Nguyen JP. Neuropathic pain controlled for more than a year by monthly sessions of repetitive transcranial magnetic stimulation of the motor cortex. Neurophysiol Clin. 2004;34:91–95  Back to cited text no. 6
    
7.Borckardt JJ, Reeves ST, Weinstein M, Smith AR, Shelley N, Kozel FA, et al. Significant analgesic effects of one session of postoperative left prefrontal cortex repetitive transcranial magnetic stimulation: a replication study. Brain Stimul. 2008;1:122–127  Back to cited text no. 7
    
8.Borckardt JJ, Weinstein M, Reeves ST, Kozel FA, Nahas Z, Smith AR, et al. Postoperative left prefrontal repetitive transcranial magnetic stimulation reduces patient-controlled analgesia use. Anesthesiology. 2006;105:557–562  Back to cited text no. 8
    
9.Rossini PM, Barker AT, Berardelli A, Caramia MD, Caruso G, Cracco RQ, et al. Non-invasive electrical and magnetic stimulation of the brain, spinal cord and roots: basic principles and procedures for routine clinical application. Report of an IFCN committee. Electroencephalogr Clin Neurophysiol. 1994;91:79–92  Back to cited text no. 9
    
10.Li X, Nahas Z, Kozel FA, Anderson B, Bohning DE, George MS. Acute left prefrontal transcranial magnetic stimulation in depressed patients is associated with immediately increased activity in prefrontal cortical as well as subcortical regions. Biol Psychiatry. 2004;55:882–890  Back to cited text no. 10
    
11.Zubieta JK, Bueller JA, Jackson LR, Scott DJ, Xu Y, Koeppe RA, et al. Placebo effects mediated by endogenous opioid activity on μ-opioid receptors. J Neurosci. 2005;25:7754–7762  Back to cited text no. 11
    
12.Gracely RH, Geisser ME, Giesecke T, Grant MAB, Petzke F, Williams DA, et al. Pain catastrophizing and neural responses to pain among persons with fibromyalgia. Brain. 2004;127:835–843  Back to cited text no. 12
    


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