Neural Activation During Tonic Pain and Interaction Between Pain and Emotion in Bipolar Disorder: An fMRI Study

Abstract

Objective: Pain and affective disorders have clear clinical relevance; however, very few studies have investigated the association between pain and bipolar disorder. This study investigated the brain activity of patients with bipolar disorder (BPs) undergoing tonic pain and assessed the interaction between pain and emotion. Methods: Ten BPs and ten healthy controls (HCs) were exposed to emotional pictures (positive, neutral, or negative), tonic pain only (pain session), and emotional pictures along with tonic pain (combined session). A moderate tonic pain was induced by the infusion of hypertonic saline (5% NaCl) into the right masseter muscle with a computer-controlled system. Whole-brain blood oxygenation level dependent (BOLD) signals were acquired using 3T functional resonance imaging (fMRI). Results: Ten BPs and ten healthy participants were included in the final analysis. During the pain session, BPs accepted more saline, but showed lower pain rating scores than HCs. When experiencing pain, BPs showed a significant decrease in the BOLD signal in the bilateral insula, left inferior frontal gyrus (IFG), and left cerebellum as compared with HCs. In the combined session, the activated regions for positive mood (pain with positive mood > baseline) in BPs were the left cerebellum, right temporal gyrus, and left occipital gyrus; the activated regions for negative mood (pain with negative mood > baseline) were the right occipital gyrus, left insula, left IFG, and bilateral precentral gyrus. Conclusions: This study presents the preliminary finding of the interaction between pain and emotion in BPs. BPs exhibited lower sensitivity to pain, and the activation of insula and IFG may reflect the interaction between emotion and pain stimulus.

Keywords: bipolar disorder; functional magnetic resonance imaging (fMRI); inferior frontal gyrus (IFG); insula; pain; visual analog scale (VAS).

Figure 1

Panels (A,B) show the VAS scores and average infusion rate of subjects during pain session. The VAS scores were recorded from the start of the scan. (A) Zero to three hundred second is baseline scanning; functional scanning began at 300 s and was completely synchronized with injection. The average infusion rate was recorded from the start of injection. (B) At the onset of infusion, a standard 0.2 mL bolus of 5% hypertonic saline solution was administered over 15 s as a tonic muscle pain stimulus; at 120 s, infusion based on VAS score was started.

Figure 2

Panels (A,B) show the active brain regions during emotional picture sessions in healthy controls (A) and patients with bipolar disorder (B). Panel (C) shows areas that exhibited significant increase in BOLD signal intensity (BPs > HCs) (p < 0.001, uncorrected).

Figure 3

Panels (A,B) show the active regions during pain session in the healthy controls (A) and patients with bipolar disorder (B). Panel (C) shows areas that exhibited significant increase in BOLD signal intensity (HCs > BPs) (p < 0 001, uncorrected).

Figure 4

Panels (A,B) show the active regions during tonic pain combined with positive or negative emotional stimuli in healthy controls (A) and patients with bipolar disorder (B) (p < .001, uncorrected).