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picture of Fadel Zeidan
2014 Mitchell Max Awardee:
Fadel Zeidan, Ph.D.
Wake Forest School of Medicine

Dr. Zeidan earned his Bachelor's degree in Psychology, Graduate Certificate in Cognitive Science, and a Master’s degree from the University of North Carolina, at Charlotte.   He then went on to earn a Ph.D. also from UNC, Charlotte with Susan Johnson and Paul Goolkasian as mentors.  Dr. Zeidan is now a post-doctoral research fellow in the Department of Neurobiology and Anatomy at Wake Forest School of Medicine in the laboratory of Robert Coghill.  He received several research awards for his work at UNC,  and while at Wake Forest he was awarded an NIH postdoctoral NRSA through NCCAM and is co-investigator on an R21 award, also through NCCAM.

Neural Mechanisms supporting Mindfulness-based Pain Relief as Compared to Placebo Analgesia

Fadel Zeidan1, Nichole M. Emerson1, Suzan Farris1, Jenna Ray2, Youngkyoo Jung3, Robert A. Kraft3, John G. McHaffie1, & Robert C. Coghill1

1Wake Forest School of Medicine, Department of Neurobiology and Anatomy; 2University of North Carolina at Charlotte, Department of Psychology; 3Wake Forest School of Medicine, Department of Biomolecular Engineering


Pain is a multidimensional subjective experience that is constructed and modulated by sensory, cognitive and affective mechanisms rendering the treatment of clinical pain challenging and a financial burden. Mindfulness meditation, a cost-effective cognitive practice, has been shown to reliably improve pain and health outcomes. However, it is still unknown if mindfulness meditation-related pain relief engages distinct neural mechanisms from placebo analgesia. For instance, mindfulness-based pain relief could simply be associated with placebo-related factors such as expectation modulation and conditioning as well as demand characteristics corresponding to the health promoting reputation of meditation. To bridge this explanatory gap, the present study employed an emerging, perfusion-based functional Magnetic Resonance Imaging (fMRI) technique (arterial spin labeling) to identify if mindfulness meditation reduces pain through distinct brain mechanisms when compared to placebo analgesia and sham mindfulness meditation.



A total of 75 healthy, pain-free participants were randomly assigned to one of four groups (mindfulness meditation; placebo-conditioning; sham mindfulness meditation; book-listening control).


The mindfulness meditation group participated in a four-day [20minute (m)/day (d)] mindfulness meditation intervention.

Across four (20m/d) placebo-induction sessions, subjects in the placebo group were conditioned to believe that an inert cream contained analgesic properties.

The main purpose of the sham mindfulness meditation intervention (4 days; 20m/d) was to lead subjects to believe they were practicing mindfulness meditation without the explicit instructions related to mindfully attending to the breath in a non-evaluative manner.

The control group listened to an audio recording of The Natural History of Selborne across four, 20m sessions.


A 16 x 16 mm surface area thermal probe (TSA-II) was employed to deliver noxious thermal stimulation (49°C).

Pain Assessment

Pain intensity/unpleasantness ratings were assessed with visual analog scales (VAS).

Experimental Procedures Overview

This study included seven individually tailored experimental sessions (n = 525). Subjects first participated in a psychophysical training to familiarize them with VAS usage and varying noxious thermal stimulation paradigms. The second experimental session (fMRI session 1) was conducted to assess for baseline group differences in behavioral and neural pain responses. The following four experimental sessions (session 3-6) included each subject’s respective group manipulation/intervention. The final experimental session (fMRI session 2) was conducted to assess for hypothesized group differences in behavioral and neural pain responses.


Importantly, there were no baseline group differences in pain intensity and unpleasantness ratings (p> .05) in fMRI session 1. We found that all of the cognitive manipulations effectively reduced pain intensity and unpleasantness ratings when compared to the control group (p < .05). Interestingly, mindfulness meditation was more effective than placebo and sham meditation at reducing pain intensity and unpleasantness ratings (p < .05). Although fMRI analyses are ongoing, preliminary findings reveal that mindfulness meditation is associated with significant thalamic and periaqueductal gray matter (PAG) deactivation when compared to the placebo, sham meditation, and control groups. 


This is the first study to identify that mindfulness meditation-related pain relief engages distinct behavioral and neural mechanisms when compared to placebo analgesia and sham mindfulness meditation.