Cathodal and Anodal Left Prefrontal tDCS and the Perception of Control Over Pain Jennifer C. Naylor, PhD,*wz Jeﬀery J. Borckardt, PhD,wy Christine E. Marx, MD,*z Robert M. Hamer, PhD,8z Sarah Fredrich, BS,w ScottT. Reeves, MD,y and MarkS. George, MDw Objectives: The prefrontal cortex may be a promising target for the use of transcranial direct current stimulation (tDCS) in the man- agement of pain symptoms. The present study explored the eﬀects of anodal and cathodal tDCS over the left dorsolateral prefrontal cortex on the eﬀects of perceived pain controllability. Materials and Methods: Forty-one participants received continuous anodal or cathodal tDCS and underwent a laboratory pain task designed to manipulate the perception of pain control. Participants were told that they would be completing a reaction-time task (press keyboard button of corresponding arrow shown on computer screen with either green or red background). A thermal pain stimulus was delivered following each trial by a thermode placed on the partic- ipant’s left forearm. Although pain stimuli were pseudorandomally ordered and matched for total duration between control (green) and noncontrol (red) trials, participants were told that if they responded correctly and more quickly on green trials than their average reaction times, the thermal pain stimulus duration would be decreased (ie, perceived control). Participants were told they had no control of pain stimulus duration over trials presented with the red background. Results: There was a signiﬁcant main eﬀect for tDCS condition (anode vs. cathode) on pain unpleasantness ratings (P < 0.04). Speciﬁcally, individuals receiving cathodal tDCS reported higher pain unpleasantness ratings (least squares mean = 69.40, SE = 3.72), whereas those receiving anodal tDCS reported lower pain unpleasantness ratings (least squares mean = 58.05, SE = 3.81). Exploratory analysis revealed a simple main eﬀect for tDCS group at the level of perceived controllability (P < 0.02). In addition, participants receiving cathodal tDCS subjectively reported feeling less control of the painful stimuli than those receiving anodal tDCS. Discussion: Left dorsolateral prefrontal cortex tDCS may play a role in modulating the neurocircuitry involved with the perception of control over pain. Key Words: pain, dorsolateral prefrontal cortex, brain stimulation, perceived control, tDCS (Clin J Pain 2014;30:693–700) P ain is rated as less intense when one believes that one has the ability to exert some amount of control over it. 1–4 Moreover, belief that one has the ability to potentially reduce the aversiveness of a painful event lessens both anticipatory anxiety and physiological arousal, 5 and has been shown to enhance tolerance to the noxious stimulus. 6 Recent work from our laboratory has shown that both intensity (sensory/discriminative dimension) and unpleas- antness (aﬀective dimension) of pain tend to be reduced when individuals perceive some controllability over the painful stimulus. 1 Several brain areas, including the pre- frontal cortices are activated when painful events are experienced as controllable, suggesting that this brain area may, in part, mediate the aﬀective experience of pain. 7 Although the role of the prefrontal cortex in pain control remains unclear, left prefrontal activation is negatively correlated with pain unpleasantness 8 and a series of non- human animal studies by Maier and colleagues have eloquently demonstrated that the perception of pain control is likely mediated by the ventral-medial pre- frontal cortex. 9–13 Thus, perceived controllability of pain appears to involve prefrontal cortical circuits and may be involved in modulation of limbic system responses to painful stimuli. High-frequency repetitive transcranial magnetic stim- ulation (rTMS) is 1 method of noninvasive brain stim- ulation that has been used to investigate the inﬂuence of the dorsolateral prefrontal cortex (DLPFC) on the analgesic eﬀects of perceived pain controllability. 1 Although it remains unclear how rTMS aﬀects the neurocircuitry involved in the pain controllability pathway, TMS of the prefrontal cortex may initiate a cascade of events that results in changes in limbic system activity. 14 Transcranial direct current stimulation (tDCS) is another minimally invasive brain stimulation technique that selectively acti- vates or inhibits speciﬁc cortical areas depending upon the polarity of stimulation. 15 Generally, cathodal stimulation results in reduced excitability and anodal stimulation results in increased excitability of neurons in the area underneath the tDCS surface electrodes. 16 The stimulation eﬀects of both TMS and tDCS are limited to the cortex, and cannot penetrate to deeper pain-related regions such as the amygdala, insula, and cingulate. Thus, TMS and tDCS both function to alter cortical neuronal activity that inﬂu- ences neuronal activity in other brain regions. Although the majority of tDCS pain studies have focused on stimulation of the motor cortex as a means to modulate the sensory aspects of pain, 17–20 the DLPFC appears to mediate aﬀective networks associated with pain. 17 Thus, tDCS of the DLPFC appears to be a rea- sonable cortical target for the treatment of the emotional dimension of pain. Recent ﬁndings from our laboratory have demonstrated that DLPFC rTMS is associated with a directional outcome suggestive of analgesia for both Received for publication January 10, 2013; revised November 29, 2013; accepted August 19, 2013. From the Departments of wPsychiatry and Behavioral Sciences, Insti- tute of Psychiatry; yAnesthesia and Perioperative Medicine, Medi- cal University of South Carolina, Charleston, SC; zDepartment of Psychiatry and Behavioral Sciences, Duke University Medical Center; *Durham Veterans Aﬀairs Medical Center, Durham; Departments of 8Psychiatry; and zBiostatistics, University of North Carolina, Chapel Hill, NC. The authors declare no conﬂict of interest. Dr Naylor is supported by a Department of Veterans Aﬀairs Rehabilitation Research and Development Career Development Award (N0908-W). Dr Marx is supported by a VA Advanced Research Career Development Award (CDTA-016-09F) and a VA Career Development Transition Award (ARCD-017-05F). Reprints: Jeﬀery J. Borckardt, PhD, Department of Psychiatry and Behavioral Sciences, Institute of Psychiatry, Medical University of South Carolina, 5 South, 67 President Ave, P.O. Box 250861, Charleston, SC 29425 (e-mail: borckard@musc.edu). Copyright r 2013 by Lippincott Williams & Wilkins ORIGINAL ARTICLE Clin J Pain  Volume 30, Number 8, August 2014 www.clinicalpain.com | 693