Mechanisms of Mindfulness Meditation-Induced Analgesia

Common brain regions activated during meditation and pain

Chronic pain is a highly prevalent disorder, affecting approximately 1.5 billion people globally.1,2 An estimated 100 million Americans experience chronic pain, with an economic burden reported to be $635 billion per year in both medical expenses and lost work productivity.1,2

The multidimensional and complex experience of pain is mediated and modulated by interacting systems involving sensory, affective and cognitive factors.3 Reports from patients with chronic pain highlight great diversity of experience, limiting the identification of underlying substrates, pathways, and mechanisms involved in its manifestation.

Increases in steroid injections and opioid treatments to manage chronic pain have led to higher Medicare expenditures. In an attempt to address the concerns of the opioid epidemic and the alarming prevalence of chronic pain worldwide, the Centers for Disease Control and Prevention have recommended the development and identification of fast-acting non-pharmacological approaches to the treatment of chronic pain.2

One method of pain relief that has been replicated both experimentally and in the clinical ecosystem is mindfulness meditation.2 With mindfulness meditation, patients are guided through a cognitive exercise in order to develop awareness of their sensory environment in the absence of a reactionary response.3

Several studies show that mindfulness meditation can effectively alleviate pain.4-6 However, limited data describing the underlying mechanisms mediating the analgesic effects of mindfulness meditation has been gathered.

In a study designed to determine whether mindfulness meditation engages pain-relieving mechanisms distinct from placebo, researchers randomly assigned healthy volunteers to 1 of 4 groups: mindfulness meditation, sham mindfulness meditation, placebo and a control condition in which subjects were asked to participate in book-listening.

Efficacy of intervention for each group was evaluated with functional neuroimaging and psychophysical assessments of pain. Notably, all groups in which patients’ cognition was “manipulated” had reduced pain levels and ratings of unpleasantness, as assessed by the visual analog scale, compared to pre-manipulation levels and control patients (ie, in the book-listening group, P <.05).

Study participants in the mindfulness meditation group, when compared to placebo and sham mindfulness meditation, respectively, had reduced pain intensity (P = .032; P = .030) and pain unpleasantness (P  <.001; P = .043).

Functional imaging showed that mindfulness meditation-associated pain relief led to activation of the orbitofrontal, anterior insular and subgenual anterior cingulated cortices, areas implicated in the cognitive modulation of pain. Analgesic effects in the placebo group were associated with activity in the dorsolateral prefrontal cortex and deactivation of regions in the secondary somatosensory cortex. Conversely, analgesia produced by sham mindfulness meditation was not associated with significant neural activity, but with reduced respiration rate. 

The authors concluded that pain is modulated by distinct cognitively driven mechanisms,postulating that mindfulness meditation results in a form of decoupling in which the individual’s subjective experience and the contextualization and/or meaning of pain is altered in reference to the self. This dissociation allows to attenuate the experience of pain through reappraisal.2  

In a follow-up study, the researchers sought to investigate the underlying mechanisms of mindfulness meditation-associated analgesic effects, and in particular, whether these are mediated by endogenous opioids.7 Opioid receptors are highly expressed in the brain regions activated during mindfulness meditation.

In this study, 78 subjects were randomized in a double-blind fashion into 1 of 4 treatment arms: mindfulness meditation + the opioid agonist naloxone; control (book listening) + naloxone; mindfulness meditation + saline; control + saline.

Subjects were then evaluated using psychophysical assessments of pain. Results indicated that individuals in the mindfulness meditation group had significantly reduced pain intensity and unpleasantness ratings, compared to those in the control group. Naloxone administration failed to eliminate the analgesic effects of mindfulness meditation, leading to the conclusion that mindfulness meditation does not engage the endogenous opioidergic system to produce its analgesic effects.7

Results from these studies point to a role of meta-cognition in facilitating engagement of a dynamic pain modulatory system, allowing to shift the individual’s attention and to appraise noxious sensations.7

More specifically, it has been proposed that during the training phase of mindfulness meditation, alterations are made to an individual’s assessment of pain as a function of self-referential processing.2 These alterations may be facilitated by a gating mechanism mediated by the thalamic reticular nuclei (TRN) which inhibits sensory processing in the thalamus – the attentional “gatekeeper” of sensory information-diminishing the conscious processing of nociceptive information by limiting its distribution throughout the cortex.7

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  1. Institute of Medicine (US). Releiving Pain in America. National Academy of Sciences 2011.
  2. Zeidan F, Vago DR. Mindfulness meditation-based pain relief: a mechanistic account. Ann N Y Acad Sci 2016;1373(1):114-127.
  3. Zeidan F, Emerson NM, Farris SR et al. Mindfulness Meditation-Based Pain Relief Employs Different Neural Mechanisms Than Placebo and Sham Mindfulness Meditation-Induced Analgesia. J Neurosci 2015;35(46):15307-15325.
  4. Jang SH, Kang SY, Lee HJ, Lee SY. Beneficial Effect of Mindfulness-Based Art Therapy in Patients With Breast Cancer-A Randomized Controlled Trial. Explore (NY) 2016.
  5. de JM, Lazar SW, Hug K et al. Effects of Mindfulness-Based Cognitive Therapy on Body Awareness in Patients with Chronic Pain and Comorbid Depression. Front Psychol 2016;7:967.
  6. Gotink RA, Meijboom R, Vernooij MW, Smits M, Hunink MG. 8-week Mindfulness Based Stress Reduction induces brain changes similar to traditional long-term meditation practice – A systematic review. Brain Cogn 2016;108:32-41.
  7. Zeidan F, Adler-Neal AL, Wells RE et al. Mindfulness-Meditation-Based Pain Relief Is Not Mediated by Endogenous Opioids. J Neurosci 2016;36(11):3391-3397.