Functional Changes of White Matter Are Related to Human Pain Sensitivity during Sustained Nociception

Abstract

Pain is considered an unpleasant perceptual experience associated with actual or potential somatic and visceral harm. Human subjects have different sensitivity to painful stimulation, which may be related to different painful response pattern. Excellent studies using functional magnetic resonance imaging (fMRI) have found the effect of the functional organization of white matter (WM) on the descending pain modulatory system, which suggests that WM function is feasible during pain modulation. In this study, 26 pain sensitive (PS) subjects and 27 pain insensitive (PIS) subjects were recruited based on cold pressor test. Then, all subjects underwent the cold bottle test (CBT) in normal (26 degrees temperature stimulating) and cold (8 degrees temperature stimulating) conditions during fMRI scan, respectively. WM functional networks were obtained using K-means clustering, and the functional connectivity (FC) was assessed among WM networks, as well as gray matter (GM)-WM networks. Through repeated measures ANOVA, decreased FC was observed between the GM-cerebellum network and the WM-superior temporal network, as well as the WM-sensorimotor network in the PS group under the cold condition, while this difference was not found in PIS group. Importantly, the changed FC was positively correlated with the state and trait anxiety scores, respectively. This study highlighted that the WM functional network might play an integral part in pain processing, and an altered FC may be related to the descending pain modulatory system.

Keywords: anxiety; brain white matter; functional connectivity; pain sensitivity.

Figure 1

Thirteen WM networks with high stability were obtained using K-means clustering algorithm. (A). WM networks in full view. (B). Stability of clustering for different numbers of clusters. The maximum K of Dice coefficient greater than 0.9 is 13. “*” denotes the most stable number of clusters. (C). Dorsal view of 13 WM networks.

Figure 2

Detail views of the WM functional networks. All WM number, full names, abbreviations and maps have a corresponding relationship.

Figure 3

There was a significant interaction between the group and the stimulus condition in the FC between networks. (A). The green bands represent the GM network, and the yellow bands represent the WM network. All band results had a p value of less than 0.005. (B). Results of post hoc tests. Among them, * represents 0.01 < p ≤ 0.05, ** represents 0.001 < p ≤ 0.01 and *** represents p ≤ 0.001.

Figure 4

The (A–C) plot is the correlation results of the PS group under normal condition. (D) shows the correlation results of the PIS group under cold condition. In PS group at normal condition, the SA-subscale score was positively correlated with pCBN–sTN FC and pCBN–PCN FC, and the TA-subscale score was positively correlated with pCBN–PCN FC. In PIS group at cold condition, the SA-subscale score was positively correlated with pCBN–PCN FC.