Background & Aims
Hippocampal circuitry has been hypothesized to play a role in the development and maintenance of chronic pain through emotional learning mechanisms[1], and smaller hippocampal volumes in sub-acute back pain patients predict which patients transition to chronic pain[2]. The extent to which these hippocampal properties are preexisting risk factors for the development of chronic pain, or instead change in response to stressors throughout the transition from acute to chronic pain remains poorly understood. In this longitudinal study, participants presenting in the emergency department with mild traumatic brain injury were scanned within 5 days of the injury, and again six months later. To disentangle between pre-existing factors and consequences, we assessed if hippocampal volumes measured at the early-acute stage are associated with pain outcomes 6 and 12 months after injury, or alternatively, if hippocampal volume changes arise over time during the transition from acute to chronic pain.
Methods
We recruited participants after a motorized vehicle accident, presenting with significant head/neck pain (mean = 54/100 NRS, SD = 30) and a diagnosis of whiplash-associated disorders and mild traumatic brain injury. Thirty-eight participants completed two MRI scans: soon after the accident (mean 49 hours, range 12-115 hours), and again 6 months later. Pain intensity was collected every month after the injury, for up to a year after the injury. Hippocampal volumes were extracted from FreeSurfer 6.0 after longitudinal registration. Linear regressions were conducted, predicting pain at 6 months from hippocampal volume collected after injury, and change in hippocampal volume between injury and 6 months; interactions with baseline anxiety were also assessed.
Results
Hippocampal volumes measured immediately after injury did not show associations with pain outcomes at 6- or 12-months post-injury. However, left hippocampal volume was reduced significantly in patients who transitioned from acute to chronic pain, with higher changes in volume being found for patients who reported the highest pain intensity at 6 months. This relationship was stronger in interaction with anxiety scores measured at the early acute stage. More specifically, patients with high anxiety after injury who also reported the highest pain at 6 months showed the largest changes in hippocampal volume. These changes in hippocampal volume, from early acute to 6 months post-injury, in interaction with anxiety, are further predictive of whether participants recover or show persistent pain 1 year later. Right hippocampal volumes were not associated with outcomes.
Conclusions
While hippocampal volumes measured immediately after injury are not associated with pain outcomes six and 12 months after mTBI, individuals experiencing persistent pain six months after injury exhibit significant hippocampal volume changes over time. Notably, heightened anxiety post-injury further contributes to these hippocampal volume alterations. While smaller hippocampal volumes have been posited as an a-priori, pre-existing risk factor in the transition from acute to chronic back pain, our findings in a distinct chronic pain model suggest that hippocampal volume is instead subject to plastic changes that occur during the acute-to-chronic pain transition, possibly driven by heightened stress and anxiety[3]. Since these changes hold predictive value beyond the 6-month time-point, we posit that they reflect maladaptive plasticity and influence chronic pain maintenance.
References
1.Baliki MN, Apkarian AV. Nociception, pain, negative moods and behavior selection. Neuron. 2015;87(3):474-91. doi: 10.1016/j.neuron.2015.06.005.
2.Vachon-Presseau E, Tetreault P, Petre B, Huang L, Berger SE, Torbey S, Baria AT, Mansour AR, Hashmi JA, Griffith JW, Comasco E, Schnitzer TJ, Baliki MN, Apkarian AV. Corticolimbic anatomical characteristics predetermine risk for chronic pain. Brain. 2016;In Press. Epub 2016/05/18. doi: 10.1093/brain/aww100. PubMed PMID: 27190016.
3.Vachon-Presseau E, Roy M, Martel M-O, Caron E, Marin M-F, Chen J, Albouy G, Plante I, Sullivan MJ, Lupien SJ, Rainville P. The stress model of chronic pain: evidence from basal cortisol and hippocampal structure and function in humans. Brain. 2013;136(3):815-27. doi: 10.1093/brain/aws371.
Presenting Author
Paulo Branco
Poster Authors
Topics
- Pain Imaging