Brain perfusion patterns are altered in chronic knee pain: a spatial covariance analysis of arterial spin labelling MRI

Iwabuchi, Sarina J.; Xing, Yue; Cottam, William J.; Drabek, Marianne M.; Tadjibaev, Arman; Fernandes, Gwen; Petersen, Kristian Kjær; Arendt-Nielsen, Lars; Graven‐Nielsen, Thomas; Valdes, Ana; Zhang, Weiya; Doherty, Michael; Walsh, David A.; Auer, Dorothee P.

doi:10.1097/j.pain.0000000000001829

Cited by 19 publications

(19 citation statements)

References 43 publications

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“…The absence of impairments in hippocampal learning and memory function in the present study is consistent with human neuroimaging findings, suggesting that knee OA impacts the hippocampus less than other chronic pain conditions [41]. However, there is also evidence that chronic pain caused by knee OA causes forebrain changes [4,5,23], and recent studies in human participants support that OA pain may contribute to cognitive impairments, reflected in measures of verbal recall and fluency, subtraction ability and attention [24,27]. These measures may partly depend on similar neurocognitive mechanisms as those assessed in the present study, although it remains to be examined if human participants with chronic OA pain are impaired on translational behavioural assays that correspond more directly to the ones used in the present study, such as a virtual DMP test [10] and CANTAB assays of executive functions, including behavioural flexibility [3].…”

Section: Chronic Oa Pain and Cognitive Deficits: Translational Relevancesupporting

confidence: 89%

“…Recent longitudinal studies show that OA pain is associated with cognitive impairments, reflected in measures of verbal recall and fluency, subtraction ability, and attention [24,27]. Moreover, grey matter changes [4] and functional reorganisation [5,23] across cortical and subcortical regions have been identified in OA patients. However, unlike chronic back pain and complex regional pain syndrome, OA patients do not have a significant loss of hippocampal volume [41].…”

Section: Introductionmentioning

confidence: 99%

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No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain

Gonçalves

Hathway

Woodhams

et al. 2022

Preprint

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Although chronic pain states have been associated with impaired cognitive functions, including memory and cognitive flexibility, the cognitive effects of osteoarthritis (OA) pain remain to be clarified. The aim of this study was to measure cognitive function in the mono-iodoacetate (MIA) rat model of chronic OA-like knee pain. We used young adult male Lister hooded rats, which are well suited for cognitive testing. Rats received either a unilateral knee injection of MIA (3mg/50uL) or saline as control. Joint pain at rest was assessed for up to 12 weeks using weight-bearing asymmetry, and referred pain at a distal site using determination of hindpaw withdrawal thresholds (PWT). The watermaze delayed-matching-to-place (DMP) test of rapid place learning, novel object recognition (NOR) memory assay and an operant response-shift and -reversal task were used to measure memory and behavioural flexibility. Open field locomotor activity, startle response, and prepulse inhibition (PPI) were also measured for comparison. MIA-injected rats showed markedly reduced weight-bearing on the injured limb, as well as pronounced cartilage damage and synovitis, but interestingly no changes in PWT. Rearing was reduced, but otherwise locomotor activity was normal and no changes in startle and PPI were detected. MIA-injected rats had intact watermaze DMP performance, suggesting no substantial change in hippocampal function, and there were no changes in NOR memory or performance on the operant task of behavioural flexibility. Our finding that OA-like pain does not alter hippocampal function, unlike other chronic pain conditions, is consistent with human neuroimaging findings.

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Section: Chronic Oa Pain and Cognitive Deficits: Translational Relevancesupporting

confidence: 89%

Section: Introductionmentioning

confidence: 99%

No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain

Gonçalves

Hathway

Woodhams

et al. 2022

Preprint

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“…In chronic pain stimulation, numerous microstructural and functional changes occur in the brain, such as synaptic plasticity, blood perfusion, and connectivity properties of the functional and structural networks ( Kuner and Flor, 2017 ; Iwabuchi et al, 2020 ; Barroso et al, 2021 ). These changes are closely related to the onset of pain, which may not only be adaptive changes in response to peripheral pain stimulation but also a key intermediate link to pain perception ( Prinsloo et al, 2014 ).…”

Section: Discussionmentioning

confidence: 99%

Evaluation of the Glymphatic System With Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain

et al. 2022

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Cancer pain (CP) is one of the most common symptoms affecting life quality, and there is considerable variation in pain experience among patients with malignant tumors. Previously, it has been found that the fluid drainage function in the brain can be regulated by peripheral pain stimulation. However, the relationship between cancer pain and functional changes of the glymphatic system (an important pathway for fluid drainage in the brain) remains unclear. In this study, 97 participants were enrolled, which included 40 participants in the cancer pain (CP) group, 27 participants in the painless cancer (PLC) group and 30 participants in the control (NC) group. Differences in glymphatic system function among the three groups and between before and after pain pharmacological intervention were analyzed by measuring diffusivity and the index along the perivascular space (ALPS index) using diffusion tensor imaging. We found that diffusivity and the ALPS index were significantly lower in the CP group than in the PLC and NC group and increased following intervention with pain relief. Moreover, the ALPS index was negatively correlated with the degree of pain in the CP group. The present study verified that alterations in glymphatic function are closely related to cancer pain, and the quantification of functional changes reflects pain severity. Our findings support the use of neuroimaging biomarkers for cancer pain assessment and indicate that pain can be alleviated by regulating brain function status.

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“…Exclusion criteria at enrolment included contraindication to MRI or significant neurological, psychiatric or other significant health problem. Further information on the subject pool (whilst recruitment was ongoing) as well as data not reported here can be found in [21].…”

Section: Participants and Inclusion Criteriamentioning

confidence: 99%

Prescription opioid-related alterations to amygdalar and thalamic functional networks in chronic knee pain: A retrospective case control resting-state connectivity study

Drabek

Cottam

Iwabuchi

et al. 2022

Preprint

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ObjectiveLong-term opioid use is associated with diminished pain relief, hyperalgesia, and addiction which is not well understood. This study aimed to characterise opioid-related brain network alterations in chronic pain, focused on the right amygdala, and left mediodorsal thalamic nuclei that play key roles in affective pain processing, and are particularly rich in mu opioid receptors (MOR).SubjectsParticipants on opioid prescriptions with painful knee osteoarthritis and matched non-opioid using control pain participants.Methods and designSeed-based functional connectivity (FC) maps from resting-state fMRI data were compared between groups.ResultsWe found right amygdala hyperconnectivity with the posterior default mode network (pDMN) and the dorsomedial prefrontal cortex in opioid users in contrast to anti-correlations in controls. Conversely, opioid users showed predominant hypoconnectivity of the left dorsomedial thalamic seed with the cingulate cortex except for the subgenual part displaying an anti-correlation in opioid users and no association in non-users. Opioid users also showed higher negative affect in exploratory post-hoc tests suggesting a potential contribution of trait anxiety to amygdala-pDMN FC alteration.ConclusionOpioid use related hyperconnectivity of the right amygdalar network likely reflects maladaptive mechanisms involving negative affect and network plasticity. Hypoconnectivity of the mediodorsal thalamic nuclei with the anterior and mid cingulate on the other hand may reflect impaired resilience in line with previously reported compensatory MOR upregulation. In conclusion, this study provides new insight into possible brain mechanisms underlying adverse effects of prolonged opioids in chronic pain and offer candidate network targets for novel interventions.

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Brain perfusion patterns are altered in chronic knee pain: a spatial covariance analysis of arterial spin labelling MRI

Cited by 19 publications

References 43 publications

No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain

No evidence for cognitive impairment in an experimental rat model of knee osteoarthritis and associated chronic pain

Evaluation of the Glymphatic System With Diffusion Tensor Imaging-Along the Perivascular Space in Cancer Pain

Prescription opioid-related alterations to amygdalar and thalamic functional networks in chronic knee pain: A retrospective case control resting-state connectivity study

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