Painful After-Sensations in Fibromyalgia are Linked to Catastrophizing and Differences in Brain Response in the Medial Temporal Lobe

Abstract

Fibromyalgia (FM) is a complex syndrome characterized by chronic widespread pain, hyperalgesia, and other disabling symptoms. Although the brain response to experimental pain in FM patients has been the object of intense investigation, the biological underpinnings of painful after-sensations (PAS), and their relation to negative affect have received little attention. In this cross-sectional cohort study, subjects with FM (n = 53) and healthy controls (n = 17) were assessed for PAS using exposure to a sustained, moderately painful cuff stimulus to the leg, individually calibrated to a target pain intensity of 40 of 100. Despite requiring lower cuff pressures to achieve the target pain level, FM patients reported more pronounced PAS 15 seconds after the end of cuff stimulation, which correlated positively with clinical pain scores. Functional magnetic resonance imaging revealed reduced deactivation of the medial temporal lobe (MTL; amygdala, hippocampus, parahippocampal gyrus) in FM patients, during pain stimulation, as well as in the ensuing poststimulation period, when PAS are experienced. Moreover, the functional magnetic resonance imaging signal measured during the poststimulation period in the MTL, as well as in the insular and anterior middle cingulate and medial prefrontal cortices, correlated with the severity of reported PAS by FM patients. These results suggest that the MTL plays a role in PAS in FM patients.

Perspective: PAS are more common and severe in FM, and are associated with clinical pain and catastrophizing. PAS severity is also associated with less MTL deactivation, suggesting that the MTL, a core node of the default mode network, may be important in the prolongation of pain sensation in FM.

Keywords: Human; default mode network; neuroimaging; psychophysics; psychosocial; sensitization; temporal summation.

Figure 1

Temporal summation to prolonged moderately painful leg cuff in subjects with FM and control subjects. A cuff was applied to the left leg and inflated to a pressure corresponding to 40/100 pain for each subject. This pressure was then held for a 2-minute period and subjects asked to rate the pain on an NRS (0–100). (A) Pain ratings at 0, 60, and 120 seconds, showing significant increase in cuff scores in FM patients, but not control subjects (mean and standard error shown). (B) Variability of response to sustained painful cuff, showing the proportion of subjects with increase in score between initiation and end of cuff stimulus (TSP), no change (NC), and with decrease in score between initiation and end of cuff stimulus (habituation; HAB), although there was no difference in these groupings between FM and control participants (χ = 2.46, P = .293). *P < .05.

Figure 2

PAS in subjects with FM and control participants. Fifteen seconds after deflation of the painful leg cuff, subjects were asked to rate any ongoing pain in their leg. (A) Subjects with FM had a significantly higher rating of PAS than control participants (mean and standard error shown). (B) Variability of PAS ratings in subjects with FM (closed triangles) and control subjects (open triangles). *P < .05.

Figure 3

Group differences in brain responses during and after painful cuff stimulus. (A) Patients showed markedly dampened deactivations during pain stimulation, and (B) in the 15-second period after stimulus offset. (C) Brain activity during the postoffset period was statistically associated with the reports of PAS measured in the behavioral visit, including in regions showing group differences (green). Scatter plots are presented for illustrative purposes. Abbreviations: aMCC, anterior middle cingulate cortex; L, left; R, right.