Hippocampal correlates of pain in healthy elderly adults

Zimmerman, Molly E.; Pan, Jullie W.; Hetherington, Hoby P.; Lipton, Michael L.; Baigi, Khosrow; Lipton, Richard B.

doi:10.1212/wnl.0b013e3181c0d454

Cited by 68 publications

(35 citation statements)

References 8 publications

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“…Poor sleep seems to reduce pain threshold and predispose to chronic pain, which may worsen sleep quality (Finan, et al, 2013). Akin to our findings in fatigue patients, hippocampal volume reduction has been reported in healthy elderly adults with increased pain duration and intensity (Zimmerman, et al, 2009). Primarily frontal cortical thickness (Chen, et al, 2016) and fronto-temporal GMV (Zhang, et al, 2013) reduction has also been described in chronic obstructive pulmonary disease.…”

Section: Discussionsupporting

confidence: 88%

Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults

et al. 2017

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Excessive daytime sleepiness (EDS) and fatigue increases with age. The aim of this study was to investigate the association between EDS and fatigue with cortical thickness and hippocampal volume in cognitively normal, late middle-aged and older adults. We performed a cross-sectional observational study of 1374 cognitively-normal subjects aged 50 years and older who had a structural MRI. Regional cortical thickness and hippocampal volume were measured. Multiple linear regression models were fit to explore associations between EDS and fatigue and structural MRI measures in different brain regions, adjusting for multiple covariates. EDS was defined as Epworth Sleepiness Scale ≥10. Fatigue severity was assessed with the Beck Depression Inventory-2. 208 participants had EDS, 27 had significant fatigue, and 11 had both. Participants with EDS or fatigue had significantly lower cognitive scores, more disturbed sleep, and medical comorbidities. The presence of EDS was associated with both global and regional atrophy, whereas fatigue was more associated with frontal and temporal changes. Cortical thinning predicted by EDS and fatigue was maximal in the temporal region with average reduction of 34.2 µm (95% CI, −54.1, −14.3; P=.001) and 90.2 µm (95% CI, −142.1, −38.2; P=.001), respectively. Fatigue was also associated with hippocampal volume reduction of −374.2 mm3 (95%CI, −670.8, −77.7; P=.013). Temporal cortical thinning predicted by presence of EDS and fatigue was equivalent to more than 3.5 and nine additional years of aging, respectively. EDS and fatigue were associated with cortical thickness reduction primarily in regions with increased age-susceptibility, which may indicate accelerated brain aging.

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Section: Discussionsupporting

confidence: 88%

Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults

et al. 2017

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“…Plasticity of hippocampal volume is also observed across a number of conditions including: (1) decreased volume in Alzheimer’s disease (Devanand et al 2007); major depression (Sheline 2003); Cushing’s disease (Starkman et al 1999); PTSD (Woon et al 2010); schizophrenia (Koolschijn et al 2010); a 20-year history of chronic perceived stress (Gianaros et al 2007); chronic inflammation (Marsland et al 2008); jet lag (Cho 2001); and acute, or as noted above, in chronic pain (Zimmerman et al 2009); (2) increased volume is observed after electroconvulsive therapy (Nordanskog et al 2010) and sustained, moderate exercise (Erickson et al 2011); and (3) vary in volume in the rostrocaudal extent of the structure with acquisition of special skills (Hufner et al 2010). Thus, our observation of altered volume in the hippocampus, while not new in central nervous system (CNS) diseases and after chronic stress conditions, is new in the context of migraine and in the context of migraine frequency.…”

Section: Discussionmentioning

confidence: 97%

Common hippocampal structural and functional changes in migraine

et al. 2012

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The hippocampus is classically involved in memory consolidation, spatial navigation and is involved in the stress response. Migraine is an episodic disorder characterized by intermittent attacks with a number of physiological and emotional stressors associated with or provoking each attack. Given that migraine attacks can be viewed as repeated stressors, alterations in hippocampal function and structure may play an important role in migraine pathophysiology. Using high-resolution magnetic resonance imaging, hippocampal morphometric and functional differences (in response to noxious heat stimulation) were compared in age and gender-matched acute episodic migraineurs with high (HF) versus low (LF) frequency of migraine attacks. Morphometric results were compared with age and gender-matched healthy control (HC) cohort. Significant larger bilateral hippocampal volume was found in LF group relative to the HF and HC groups suggestive of an initial adaptive plasticity that may then become dysfunctional with increased frequency. Functional correlates of greater deactivation (LF > HF) in the same hippocampal regions in response to noxious stimulation was also accompanied by overall reduction in functional connectivity of the hippocampus with other brain regions involved in pain processing in the HF group. The results implicate involvement of hippocampus in the pathophysiology of the migraine.

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“…Many investigators have evaluated the role of the hippocampus in pain processing in human and animal studies (Bingel et al, 2002; Duric and McCarson, 2006; Schweinhardt et al, 2006; Zimmerman et al, 2009). Neuroimaging studies have shown that the hippocampus is activated in response to painful stimuli in healthy volunteers (Bingel et al, 2002).…”

Section: Inroductionmentioning

confidence: 99%

“…Furthermore, adults with chronic pain syndromes have functional and anatomical alterations in brain regions involved in pain processing including the hippocampus, the thalamus, the basal ganglia and amygdala as well as cingulate, prefrontal and somatosensory cortex (Schweinhardt and Bushnell, 2010). In older adults, higher levels of pain severity have been associated with both reductions in hippocampal volume (HV) and lower NAA levels in the hippocampus (Zimmerman et al, 2009). Alterations in specific transmitters have been demonstrated.…”

Section: Inroductionmentioning

confidence: 99%

Hippocampal subfields differentially correlate with chronic pain in older adults

et al. 2014

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Although previous studies have demonstrated that the hippocampus plays a role in pain processing, the role of hippocampal subfields is uncertain. The goal of this study was to examine the relationship between hippocampal subfield volumes and chronic pain in nondemented older adults. The study sample included 86 community-residing adults age 70 or older who were free of dementia and recruited from the Einstein Aging Study. Chronic pain was defined as pain over the last 3 months, that was moderate or severe (minimum rating of 4 out of 10) most, or all of the time. Hippocampal subfield volumes were estimated using FreeSurfer software. We modeled the association between chronic pain and hippocampal and subfield volume using linear regression. The sample had a mean age of 80 and was 58% female. Chronic pain, present in 55% of the sample, was associated with smaller right and total hippocampal volumes, particularly in women, after adjusting for age, education, and intracranial volume (eTICV). In addition, in women, volume was significantly reduced in participants with chronic pain in right CA2–3 (β=−0.35, p=0.010), right CA4-DG (β=−0.35, p=0.011), left presubiculum (β=−0.29, p=0.030), and left fimbria (β=−0.30, p=0.023). In men, chronic pain was not associated with the volume of any of the hippocampal subfield volumes. Chronic pain in women is associated with a reduction in the volume of right hippocampus and also selected hippocampal subfields. Future studies should clarify the mechanisms underlying the association between regional hippocampal volumes and chronic pain, particularly in women.

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Hippocampal correlates of pain in healthy elderly adults

Cited by 68 publications

References 8 publications

Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults

Excessive daytime sleepiness and fatigue may indicate accelerated brain aging in cognitively normal late middle-aged and older adults

Common hippocampal structural and functional changes in migraine

Hippocampal subfields differentially correlate with chronic pain in older adults

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