MRI structural brain changes associated with sensory and emotional function in a rat model of long-term neuropathic pain

Abstract

In human conditions, chronic pain is associated with widespread anatomical changes in the brain. Nevertheless, little is known about the time course of these changes or the relationship of anatomical changes to perception and behaviour. In the present study, we use a rat model of neuropathic pain (spared nerve injury, SNI) and 7 T MRI to determine the longitudinal supraspinal changes associated with pain-like and anxiety-like behaviours. SNI rats and sham controls were scanned at seven time points, 1 week before surgery, 2 weeks after, and then once a month for 5 months. At each time point we performed behavioural tests, including thermal and mechanical sensitivity, and tests of locomotion and exploratory behaviour (open field and elevated plus maze). We found that SNI rats had early and sustained thermal and mechanical hyperalgesia, and developed anxiety-like behaviours several months after injury. Compared to sham controls, SNI rats had decreased frontal cortex volumes several months after surgery, coincident with the onset of anxiety-like behaviours. There was also decreased volume in retrosplenial and entorhinal cortices. We also explored areas that correlated with mechanical hyperalgesia and found that increased hyperalgesia was associated with decreased volumes in bilateral S1 hindlimb area, anterior cingulate cortex (ACC, areas 32 and 24), and insula. Overall, our results suggest that long-term neuropathic pain has widespread effects on brain anatomy related to the duration and magnitude of the pain.

Pain imaging in health and disease — how far have we come?

“…Second, a longitudinal MRI study in a rat model of neuropathic pain (spared nerve injury) demonstrated the occurrence of prefrontal gray matter alterations several months after pain induction by surgery (104). This study provides another very interesting piece of information: the gray matter alterations in the PFC coincided with the development of anxiety-like behavior (104), emphasizing behavioral consequences of prolonged pain states. Although the mechanisms underlying gray matter alterations in chronic pain are currently unknown, a recently conducted study suggests a possibility.…”

Validation of an air-puff passive-avoidance paradigm for assessment of aversive learning and memory in rat models of chronic pain

“…The mechanism underlying cognitive impairment in chronic pain has yet to be elucidated, but it has been hypothesised that pain-related alterations in brain structure and plasticity may in turn affect cognition (Moriarty et al, 2011). A study by Seminowicz et al (2009) found anatomical alterations in brain regions associated with cognition following peripheral nerve injury in rats, but these alterations were not observed until several months post-surgery. Therefore, although we observed robust, consistent expression of chronic pain-like behaviours at the post-surgery time-point selected for passive-avoidance testing, it is possible that cognitive impairment, as assessed using this paradigm, may not have developed by this time-point.…”

Genotype-dependent responsivity to inflammatory pain: A role for TRPV1 in the periaqueductal grey

“…SNI (spared nerve injury) model of neuropathic pain was associated with a decrease in the volume of ACC and insula, and in anxiety-related tests (EPM and OF) indicated a decrease in volume of PFC correlated with the behavioural changes (Seminowicz et al, 2009). …”