Altered Reward Processing and Sex Differences in Chronic Pain

Abstract

Chronic pain and reward processing are understood to be reciprocally related to one another. Previous studies of reward processing in chronic pain patients have reported incongruent findings. While several factors likely contribute to these disparate findings, these previous studies did not stratify their analyses by sex-a factor previously shown to robustly impact reward-related responses. Thus, we examined sex as a factor of interest in level of striatal activation during anticipation of monetary incentives among patients with chronic non-specific back pain and healthy controls (HC). This study utilized functional magnetic resonance imaging during a monetary incentive delay task to evaluate reward and loss responsivity in the striatum among males and females with and without chronic pain (N = 90). Group, sex, and group-by-sex interactions were analyzed via repeated measures analysis of variance. Among HC, males exhibited significantly greater blood oxygen level dependent (BOLD) signal in the striatum during reward anticipation, particularly during large reward trials. By contrast, no significant sex differences were observed among patients. A significant group-by-sex interaction was also observed, revealing diminished BOLD responses among males with chronic pain relative to control males. These results provide novel evidence of sex-specific reductions in anticipatory responses to reward in patients with chronic pain. Altered striatal reward responsivity among males, but not females, suggests that the reward systems of males and females are uniquely disrupted by chronic pain, and highlights the value of including sex as a factor of interest in future studies of reward responsivity in the context of persistent pain.

Keywords: chronic pain; fMRI; reward processing; sex differences; striatum.

FIGURE 1

Group by sex interactions during reward and loss anticipation. During large reward trials (relative to neutral), control males exhibited significantly greater reward-related activation than control females; this difference was not observed between patient males and females. Significant differences were observed between control males and females for large rewards (p = 0.002) and medium rewards (p = 0.04). No such differences were observed between patient males and females (p = 0.89, p = 0.42, respectively). Significant differences were also observed between control males and patient males for large rewards (p = 0.002), medium rewards (p = 0.001), and small rewards (p = 0.005). No such differences were noted between control females and patient females (p > 0.40). During large loss trials (relative to neutral), control males exhibited significantly greater loss-related activation than control females (p = 0.02); this difference was not observed between patient males and females. Significant differences were also observed between control males and patient males for large rewards (p = 0.04). No such differences were noted between control females and patient females. Error bars represent confidence intervals. VS, ventral striatum. * denotes significant differences.

FIGURE 2

Ventral striatal responses to incentive anticipation vary by sex and group. Bars represent ventral striatal response to anticipation of each incentive broken down by sex or group then examined as a function of salience and valence. (A), Salience-by-Group; (B), Valence-by-Group; (C), Salience-by-Sex; (D), Valence-by-Sex. Error bars represent confidence intervals. VS, ventral striatum. * denotes significant differences.

FIGURE 3

Correlations between pain intensity and ventral striatal responses during reward. Ventral Striatal BOLD during reward anticipation collapsed across all magnitudes was differentially correlated with McGill Pain Intensity scores among males (r = 0.12, p = 0.66) and females (r = 0.43, p = 0.04). VS, ventral striatum.