Central pain modulatory mechanisms of attentional analgesia are preserved in fibromyalgia

Abstract

Fibromyalgia is a prevalent pain condition that is associated with cognitive impairments including in attention, memory, and executive processing. It has been proposed that fibromyalgia may be caused by altered central pain processing characterised by a loss of endogenous pain modulation. We tested whether attentional analgesia, where cognitive engagement diminishes pain percept, was attenuated in patients with fibromyalgia (n = 20) compared with matched healthy controls (n = 20). An individually calibrated, attentional analgesia paradigm with a 2 × 2 factorial design was used with brain and brainstem-focussed functional magnetic resonance imaging. Patients with fibromyalgia had both lower heat pain thresholds and speeds in a visual attention task. When this was taken into account for both attentional task and thermal stimulation, both groups exhibited an equivalent degree of attentional analgesia. Functional magnetic resonance imaging analysis showed similar patterns of activation in the main effects of pain and attention in the brain and brainstem (with the sole exceptions of increased activation in the control group in the frontopolar cortex and the ipsilateral locus coeruleus). The attentional analgesic effect correlated with activity in the periaqueductal gray and rostral ventromedial medulla. These findings indicate that patients with fibromyalgia can engage the descending pain modulatory system if the attentional task and noxious stimulus intensity are appropriately titrated.

Figure 1.

Quantitative sensory testing and calibration. Quantitative sensory testing showed that patients with fibromyalgia had smaller (A) heat pain thresholds, (B) cold pain threshold, and (C) pressure pain threshold. (D) Patients with fibromyalgia also had an elevated warm detection threshold. (E) The thermode temperature used for the high-thermal stimulus was lower in patients with fibromyalgia. (F) The inter-character interval for the RSVP task was longer in the patients with fibromyalgia. Data presented as mean ± SEM and comparison between groups with unpaired t test except for (C–E) which are median [IQR] and analysed with the Mann–Whitney test (*P < 0.05, **P < 0.01). IQR, interquartile range; RSVP, rapid serial visual presentation.

Figure 2.

Pain ratings during the attentional analgesia experiment. (A) Pain ratings for each subject across experimental conditions (easy and hard task and low and high temperatures) pooled across groups (n = 40), and the same data are shown (B) split into patients with fibromyalgia (n = 20) and (C) healthy controls alone (n = 20). Mixed ANOVA showed a main effect of temperature and a task × temperature interaction mediated by a reduction in the pain scores in the hard|high condition (planned post-hoc paired t test). Mean ± SEM. (***P < 0.001). ANOVA, analysis of variance.

Figure 3.

Task performance (d') in the scanner showing that the hard task was more challenging than the easy task for both (A) patients with fibromyalgia and (B) healthy controls. Mean ± SEM (mixed ANOVA, main effect of task ***P < 0.001). ANOVA, analysis of variance.

Figure 4.

(A) Main effect of temperature in patients with fibromyalgia and healthy controls in the whole brain, showing activity in the dorsal posterior insula (dpIns), anterior cingulate cortex (ACC), and primary somatosensory cortex (S1) among others (Z > 3.1 cluster-corrected P < 0.05), and in the rostral ventromedial medulla (RVM, TFCE corrected P < 0.05). (B) Group difference in the main effect of temperature in the whole brain showing a stronger response in healthy controls in both Brodmann area 10 (BA10, Z > 3.1 cluster-corrected P < 0.05) and in the left locus coeruleus (LC, TFCE corrected P < 0.05). The correlation between main effect of temperature in LC and difference in temperatures between low and high (Pearsons R = 0.49, P = 0.002, dotted 95% confidence interval). OPC, operculum; Pcu, precuneus; TFCE, threshold free cluster enhancement.

Figure 5.

Main effect of task. Main effect of task in the pooled data from patients with fibromyalgia and healthy controls (A) in the whole brain, showing increased activity in the lateral occipital cortex (LOC), anterior insula (aIns), and anterior cingulate cortex (ACC) (red–yellow) and a decrease in activity in the precuneus (Pcu), lateral occipital cortex, and the frontomedial cortex (FMC, Z > 3.1 cluster-corrected P < 0.05). (B) Main effect of task in the brainstem: in the periaqueductal gray (PAG), RVM, and left LC (TFCE corrected P < 0.05). PAG, periaqueductal gray; RVM, rostral ventromedial medulla; SPL, superior parietal lobule. TFCE, threshold-free cluster enhancement.

Figure 6.

Direct relationship between BOLD and analgesia. Activity in the PAG and the RVM correlates with the attentional analgesic effect. Inter-subject parametric regression between BOLD in PAG and RVM with the analgesic effect (ie, delta pain ratings of easy|high—hard|high), (P < 0.05, TFCE corrected). PAG, periaqueductal gray; RVM, rostral ventromedial medulla; TFCE, threshold-free cluster enhancement.