MRI-based brain morphometry correlates of chronic pain in knee osteoarthritis

Chronic pain is a complex experience that involves sensory, emotional, and cognitive aspects. The neurobiological mechanisms are therefore expected to be complex, widespread and largely maladaptive. Recent research of neuroimaging in chronic pain suggests cerebral re-organization on a structural level as a consequence of chronic pain. However, a combined and large-scale brain morphological profile in chronic pain to investigate its neural substrates has not been elucidated. The research presented aims to investigate morphological brain correlates and putatively related behavioural and cognitive aspects of chronic pain due to primary nociceptive knee osteoarthritic disorder using advanced imaging techniques for manual, voxel-based, and surface-based analysis, and questionnaire-based participants’ characterization. 31 participants with chronic painful knee osteoarthritis (age= 64.6± 8.4 years, 15 females, mean duration of pain=9.6 years) and 22 healthy controls (age= 61.3± 7.5, 13 females) underwent high-resolution anatomical MRI at 3 Tesla, and detailed pain characterization and psychometric assessment. Findings from this thesis challenge the common belief that chronic pain leads to hippocampal volume reduction and allegedly cognitive dysfunction. Indeed, general cognitive function and delayed recall memory were normally preserved in the studied cohort, and moreover the hippocampal volume was significantly enlarged. The volume of the rostral part (emotional) of anterior cingulate showed significant positive correlation with pain catastrophizing behaviour suggesting that it may underlie the pain catastrophizing tendency in patients with chronic knee pain. Higher scores of mechanical pain sensitivity correlated with reduced cortical thickness in the anterior cingulate indicating its potential key role in the process of central pain sensitization. Sufferers of chronic knee OA pain exhibited less grey matter volume in the left dorsolateral prefrontal cortex, which has a modulatory role in nociceptive transmission namely, pain perception inhibitory effect. Although the mechanism of this reduction is unknown, such a change may suggest functional disturbance with subsequent aberrant contribution to pain sustainability and chronification. Whole brain cortical thickness was investigated in patients and results revealed wide spread cortical thinning progresses with pain duration, preferentially in females, and in areas largely outside the known pain matrix, but including the posterior default mode network. Finally, preliminary results from investigating the potential mechanism of chronic pain related neocortical plasticity will be presented that may provide framework for future studies

MRI-based brain morphometry correlates of chronic pain in knee osteoarthritis

Chronic pain is a complex experience that involves sensory, emotional, and cognitive aspects. The neurobiological mechanisms are therefore expected to be complex, widespread and largely maladaptive. Recent research of neuroimaging in chronic pain suggests cerebral re-organization on a structural level as a consequence of chronic pain. However, a combined and large-scale brain morphological profile in chronic pain to investigate its neural substrates has not been elucidated. The research presented aims to investigate morphological brain correlates and putatively related behavioural and cognitive aspects of chronic pain due to primary nociceptive knee osteoarthritic disorder using advanced imaging techniques for manual, voxel-based, and surface-based analysis, and questionnaire-based participants’ characterization. 31 participants with chronic painful knee osteoarthritis (age= 64.6± 8.4 years, 15 females, mean duration of pain=9.6 years) and 22 healthy controls (age= 61.3± 7.5, 13 females) underwent high-resolution anatomical MRI at 3 Tesla, and detailed pain characterization and psychometric assessment. Findings from this thesis challenge the common belief that chronic pain leads to hippocampal volume reduction and allegedly cognitive dysfunction. Indeed, general cognitive function and delayed recall memory were normally preserved in the studied cohort, and moreover the hippocampal volume was significantly enlarged. The volume of the rostral part (emotional) of anterior cingulate showed significant positive correlation with pain catastrophizing behaviour suggesting that it may underlie the pain catastrophizing tendency in patients with chronic knee pain. Higher scores of mechanical pain sensitivity correlated with reduced cortical thickness in the anterior cingulate indicating its potential key role in the process of central pain sensitization. Sufferers of chronic knee OA pain exhibited less grey matter volume in the left dorsolateral prefrontal cortex, which has a modulatory role in nociceptive transmission namely, pain perception inhibitory effect. Although the mechanism of this reduction is unknown, such a change may suggest functional disturbance with subsequent aberrant contribution to pain sustainability and chronification. Whole brain cortical thickness was investigated in patients and results revealed wide spread cortical thinning progresses with pain duration, preferentially in females, and in areas largely outside the known pain matrix, but including the posterior default mode network. Finally, preliminary results from investigating the potential mechanism of chronic pain related neocortical plasticity will be presented that may provide framework for future studies

Cerebral Cortical Thickness in Chronic Pain Due to Knee Osteoarthritis: The Effect of Pain Duration and Pain Sensitization

ObjectiveThis study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis.MethodsWhole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females).ResultsCortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (

Cerebral cortical thickness in chronic pain due to knee osteoarthritis: the effect of pain duration and pain densitization

Objective This study investigates associations between cortical thickness and pain duration, and central sensitization as markers of pain progression in painful knee osteoarthritis. Methods Whole brain cortical thickness and pressure pain thresholds were assessed in 70 participants; 40 patients with chronic painful knee osteoarthritis (age = 66.1± 8.5 years, 21 females, mean duration of pain = 8.5 years), and 30 healthy controls (age = 62.7± 7.4, 17 females). Results Cortical thickness negatively correlated with pain duration mainly in fronto-temporal areas outside of classical pain processing areas (p<0.05, age-controlled, FDR corrected). Pain sensitivity was unrelated to cortical thickness. Patients showed lower cortical thickness in the right anterior insula (p<0.001, uncorrected) with no changes surviving multiple test correction. Conclusion With increasing number of years of suffering from chronic arthritis pain we found increasing cortical thinning in extended cerebral cortical regions beyond recognised pain-processing areas. While the mechanisms of cortical thinning remain to be elucidated, we show that pain progression indexed by central sensitization does not play a major role

Characteristics of study participants.

<p>Characteristics of study participants.</p

Cortical surface maps showing thinner cortex with log-transformed longer pain duration (right hemisphere; top, and left hemisphere; bottom).

<p>Significance at p<0.05 FDR-corrected for multiple comparisons and controlled for age.</p

Demographic data and pain characteristics of short vs. long pain duration groups.

<p>Demographic data and pain characteristics of short vs. long pain duration groups.</p

Cerebral Cortical Thickness in Chronic Pain Due to Knee Osteoarthritis: The Effect of Pain Duration and Pain Sensitization - Fig 2

<p>Scatter plots showing negative correlations of cortical thickness with log-transformed pain duration for four regions showing strongest associations (a-d; right pars orbitalis and inferior parietal, and left rostral middle frontal and frontal pole, respectively).</p

Clusters of significant negative correlation with pain duration reported at the peak coordinates, (Rt. & Lt. hemispheres).

<p>Clusters of significant negative correlation with pain duration reported at the peak coordinates, (Rt. & Lt. hemispheres).</p