The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain

Abstract

The dorsolateral prefrontal cortex (DLPFC) is a functionally and structurally heterogeneous region and a key node of several brain networks, implicated in cognitive, affective, and sensory processing. As such, the DLPFC is commonly activated in experimental pain studies, and shows abnormally increased function in chronic pain populations. Furthermore, several studies have shown that some chronic pains are associated with decreased left DLPFC gray matter and that successful interventions can reverse this structural abnormality. In addition, studies have indicated that noninvasive stimulation of the left DLPFC effectively treats some chronic pains. In this article, we review the neuroimaging literature regarding the role of the DLPFC and its potential as a therapeutic target for chronic pain conditions, including studies showing the involvement of the DLPFC in encoding and modulating acute pain and studies demonstrating the reversal of DLPFC functional and structural abnormalities after successful interventions for chronic pain. We also review studies of noninvasive brain stimulation of the DLPFC showing acute pain modulation and some effectiveness as a treatment for certain chronic pain conditions. We further discuss the network architecture of the DLPFC, and postulate mechanisms by which DLPFC stimulation alleviates chronic pain. Future work testing these mechanisms will allow for more effective therapies.

Perspective: The structure and function of the DLPFC is abnormal in some chronic pain conditions. Upon successful resolution of pain, these abnormalities are reversed. Understanding the underlying mechanisms and the role of this region can lead to the development of an effective therapeutic target for some chronic pain conditions.

Keywords: Orofacial pain; brain function; magnetic resonance imaging; morphometrics; pain; treatment planning.

Copyright © 2017 American Pain Society. Published by Elsevier Inc. All rights reserved.

Figures

Figure 1

Regions of the brain comprising the dorsolateral prefrontal cortex (DLPFC), including Brodmann Area 8, 9 and the dorsal part of 46. The three clusters shown represent subregions of the DLPFC based on a parcellation scheme by Sallet and colleagues . The DLPFC is a large, heterogenous brain region spanning the middle frontal gyrus and the lateral aspects of the superior frontal gyrus. It is banked by the inferior frontal sulcus on the lateral side, the precentral sulcus on the posterior bank, and the frontal polar cortex on the anterior bank.

Figure 2

The dorsolateral prefrontal cortex is a large, heterogeneous cortical region shown in green on a standard brain. The DLPFC is involved in multiple processes, and while it has been implicated in pain regulation, the mechanisms are unclear. Here we outline how DLPFC could affect pain through several networks, including: controlling the regulation of cognitive networks (cognitive control network) through effective switching of default mode network and extrinsic mode network; enhancing activity in a network involved in descending modulation of pain; reducing emotional reactivity to pain through reward/fear circuitry. Some studies have also provided evidence of effectiveness of left DLPFC stimulation to treat chronic pain. The right panel provides the labels of the brain regions within each of these networks. Abbreviations: Amyg – amygdala; ant – anterior; mPFC – medial prefrontal cortex; PAG – periaqueductal gray; PCu/PCC – precuneus/posterior cingulate cortex; pACC – pregenual anterior cingulate cortex; PMV – ventral premotor cortex; PPC – posterior parietal cortex; Thal – thalamus; vlPFC – ventrolateral prefrontal cortex; vStriatum – ventral striatum.