An article recently published in PLoS ONE reports an association between pain duration and fronto-temporal cortical thickness, a region not commonly associated with pain processing, in patients with chronic arthritis.¹

Previous studies have established a link between cortical volume of regions not directly mediating pain responses and chronic pain. In particular, a study published in the Journal of Pain by Rachel F. Smallwood, PhD, and colleagues showed that patients experiencing chronic pain had reduced grey matter volume in regions associated or not with pain processing – known as “pain matrix” regions – compared with healthy individuals.²

In addition, brain areas involved in cognitive and affective processes, including the right hippocampus and parahippocampal gyrus, had increased volume in those patients. The chronic pain-associated morphometric changes, detected in regions not associated with perception, might underlie common pain comorbidities, including impairments in cognitive and emotional processing, according to the study authors.

In another study, rheumatoid arthritis (RA) patients were shown to display increased basal ganglia gray matter content compared with control subjects.³ As these structures are implicated in motor control, pain processing, and responses to aversive stimuli, the authors hypothesized that RA-related structural changes may result from affected motor or pain processing.

A series of studies indicating correlations between pain sensitivity and cortical thickness in healthy subjects^4-6 suggest that central sensitization might be responsible for thinning of the anterior cingulate cortex, a region implicated in this process.⁷

Pain experienced by osteoarthritis (OA) patients is thought to result mainly from joint tissue damage-related nociceptive mechanisms. However, the role of central sensitization mechanisms is gaining recognition, as these processes are thought to underlie the development of chronic pain following knee replacement surgery.⁸

In the current study, the researchers measured the cortical thickness of 40 patients (age = 66.09± 8.47; 21 females), with knee OA-associated chronic pain, defined as lasting for over 3 months and experienced “most of the day and on most days of the week for at least the last month” and compared them to 30 healthy, non-OA controls (age = 62.72± 7.44; 17 females) using surface-based analysis of high-resolution 3 Tesla magnetic resonance imaging (MRI).¹

No significant differences in average cortical thickness were observed between healthy controls and patients with knee OA. However, OA patients had thinner cortex in the right, but not left anterior insula compared with controls (uncorrected; P <.001).

In addition, patients experiencing pain for long, but not short durations had reduced cortical thickness in the left precuneus (uncorrected; P <.001), as well, as Brodmann areas 9 and 11 (rostral middle frontal), 21 (inferior temporal) and 6 (superior frontal) compared to healthy controls (P <.05 for all Brodmann areas; FRD-corrected). No differences in average cortical thickness were detected between long- and short-term OA patients.

The authors concluded that knee OA was associated with cortical thinning “in areas extending beyond classical pain processing areas with longer duration of chronic pain independent from age and pain sensitivity.” Neither the presence of pain comorbidities, such asmood disorders, or central sensitization mechanisms were thought to underlie those observed changes. They added that  “morphometric changes are not predisposing factors but acquired as a result of the chronic pain experience.”

Limitations and Disclosures

In order to establish a causal relationship between cortical thickness and pain duration, longitudinal studies should be conducted.

The authors report no relevant disclosures.

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References

1. 1.Alshuft HM, Condon LA, Dineen RA, Auer DP. Cerebral cortical thickness in chronic pain due to knee osteoarthritis: The effect of pain duration and pain sensitization. PLoS ONE. 2016;11(9):e0161687.
2. Smallwood RF, Laird AR, Ramage AE, et al. Structural brain anomalies and chronic pain: a quantitative meta-analysis of gray matter volume. J Pain. 2013;14(7):663-675.
3. Wartolowska K, Hough MG, Jenkinson M, Andersson J, Wordsworth BP, Tracey I. Structural changes of the brain in rheumatoid arthritis. Arthritis Rheum. 2012;64(2):371-379.
4. Schwedt TJ, Chong CD. Correlations between brain cortical thickness and cutaneous pain thresholds are atypical in adults with migraine. PLoS ONE. 2014;9(6):e99791.
5. Erpelding N, Moayedi M, Davis KD. Cortical thickness correlates of pain and temperature sensitivity. Pain. 2012;153(8):1602-1609.
6. Stankewitz A, Valet M, Schulz E, et al. Pain sensitisers exhibit grey matter changes after repetitive pain exposure: a longitudinal voxel-based morphometry study. Pain. 2013;154(9):1732-1737.
7. Chen FL, Dong YL, Zhang ZJ, et al. Activation of astrocytes in the anterior cingulate cortex contributes to the affective component of pain in an inflammatory pain model. Brain Res Bull. 2012;87(1):60-66.
8. Malfait AM, Schnitzer TJ. Towards a mechanism-based approach to pain management in osteoarthritis. Nat Rev Rheumatol. 2013;9(11):654-664.