Brain activity changes associated with pain perception variability.

Pain perception can be modulated by several factors. Phenomena like temporal summation leads to increased perceived pain, whereas behavioral conditioning can result in analgesic responses. Furthermore, during repeated, identical noxious stimuli, pain intensity can vary greatly in some individuals. Understanding these variations is important, given the increase in investigations that assume stable baseline pain for accurate response profiles, such as studies of analgesic mechanisms. We utilized functional magnetic resonance imaging to examine the differences in neural circuitry between individuals displaying consistent pain ratings and those who experienced variable pain during a series of identical noxious stimuli. We investigated 63 healthy participants: 31 were assigned to a "consistent" group, and 32 were assigned to a "variable" group dependent on pain rating variability. Variable pain ratings were associated with reduced signal intensity in the dorsolateral prefrontal cortex (dlPFC). Furthermore, the dlPFC connectivity with the primary somatosensory cortex and temperoparietal junction was significantly reduced in variable participants. Our results suggest that investigators should consider variability of baseline pain when investigating pain modulatory paradigms. Additionally, individuals with consistent and variable pain ratings differ in their dlPFC activity and connectivity with pain-sensitive regions during noxious stimulation, possibly reflecting the differences in attentional processing and catastrophizing during pain.

Dorsal raphe nucleus and harm avoidance: A resting-state investigation.

The temperament dimension of harm avoidance defines an individual's biological tendency to exhibit altering levels of anxious, inhibiting, and cautious behavior. High harm avoidance and anxiety are highly comorbid, likely due to activity in similar neural circuitries involving the dorsal raphe nucleus. Despite the many investigations that have explored personality factors and brain function, none have determined the influence of ongoing activity within dorsal raphe networks on harm avoidance. The aim of this study was to explore such a relationship. In 62 healthy subjects, a series of 180 functional magnetic resonance images covering the entire brain were collected, and each subject completed the 240-item TCI-R questionnaire. Independent component analyses were performed to define the dorsal raphe network and then to determine the regions significantly correlated with harm avoidance. The independent component analyses revealed three signal intensity fluctuation maps encompassing the dorsal raphe nucleus, showing interactions with regions of the amygdala, hippocampus, nucleus accumbens, and prefrontal, insular, and cingulate cortices. Within these systems, the resting signal intensity was significantly coupled to harm avoidance in the bilateral basal amygdala, bilateral ventral hippocampus, bilateral insula, bilateral nucleus accumbens, and medial prefrontal cortex. Note that we could not measure serotonergic output, but instead measured signal changes in the dorsal raphe that likely reflect synaptic activity. These data provide evidence that at rest, signal intensity fluctuations within the dorsal raphe networks are related to harm avoidance. Given the strong relationship between harm avoidance and anxiety-like behaviors, it is possible that ongoing activity within this identified neural circuitry can contribute to an individual developing anxiety disorders.