Background & Aims

Chronic pain is a disease with a high prevalence in the world and is a major social and medical-economic burden. In Japan one in five people have chronic pain, and its prevalence will increase as Japanese are aging population [1].
Previous brain imaging studies for chronic low back pain have showed functional and structural alterations in the central nervous system [2].
Other brain imaging studies report solid evidence that specific region of the central nervous system such as DLPFC had altered gray matter density in chronic pain patients and speculated its role for controlling the pain [3].
This study was conducted in the interdisciplinary pain center of keio university hospital.
The aim of this study is to identify brain alterations of chronic neck pain (CNP) patients compared to age-sex matched healthy controls and to validate the findings in the other dataset of chronic pain patients.

Methods

We recruited 21 CNP patients and 21 age-sex matched HC and age-sex matched 23 patients with primary chronic pain (PCP) including headache and musculoskeletal pain.
Brain imaging data was acquired using 3 tesla magnetic resonance imaging (MRI) to compare brain structure by T1-weighted image (voxel size = 1 × 1 × 1 mm), and 8 minutes of resting state functional MRI (rs-fMRI) to analyze brain functional connectivity (FC). After preprocessing the MRI image, we compared gray matter density between CNP and HC using the voxel-based morphometry (VBM). Seed-based analysis was performed using the identified cluster as a seed, to examine FC alterations between CNP and HC. Significant cluster was defined as a threshold, z-score > 3.0 and familywise error (FWE)-corrected p-value (p-FWE) < 0.05. GMD and FC in the identified cluster were compared between PCP and HC again. DLPFC analysis We also investigated associations of the identified brain outcomes with behavioral measures.

Results

Averaged pain intensity and median of pain duration were 47.6 and 36 months in CNP and 62.3 and 53 months in PCP.
VBM in the whole brain analysis identified decreased GMD of the left DLPFC in CNP compared to HC (p < 0.05). PCP patients also showed decreased GMD of the identified cluster (p =0.001). FC analysis of left DLPFC as a seed identified significantly lower FC to the right hippocampus in CNP compared to HC (p < 0.001). The identified FC was negatively correlated to activity avoidance, which is subscale of the Tampa scale for kinesiophobia (p = 0.008, r = -0.57). However, PCP patients shows no significance of the decreased FC between the left DLPFC and the right hippocampus, also showed no significant correlation between GMD and behavioral data including psychological measure.

Conclusions

Decreased GMD of the left DLPFC in CNP was consistent with previous studies in patients with chronic low back pain [2]. In addition, replication of the finding in another dataset of PCP suggests decrease of volume of the DLPFC may be a biomarker of chronic pain.
Previous study showed GMD of the DLPFC and pain intensity were negatively correlated, however our study did not show such correlation [2]. This might be explained by difference of pain location or patients’ nationality.
FC analysis did not show consistent result in this study, the reason may be the lack of number of patients analyzed in this study. Further study is required to confirm these findings.

References

1.Nakamura M, Nishiwaki Y, Ushida T, Toyama Y. Prevalence and characteristics of chronic musculoskeletal pain in Japan. J Orthop Sci. 2011 Jul;16(4):424-32. doi: 10.1007/s00776-011-0102-y. Epub 2011 Jun 16. PMID: 21678085; PMCID: PMC3140943.
2.Apkarian AV, Sosa Y, Sonty S, Levy RM, Harden RN, Parrish TB, Gitelman DR. Chronic back pain is associated with decreased prefrontal and thalamic gray matter density. J Neurosci. 2004 Nov 17;24(46):10410-5. doi: 10.1523/JNEUROSCI.2541-04.2004. PMID: 15548656; PMCID: PMC6730296.
3.Seminowicz DA, Moayedi M. The Dorsolateral Prefrontal Cortex in Acute and Chronic Pain. J Pain. 2017 Sep;18(9):1027-1035. doi: 10.1016/j.jpain.2017.03.008. Epub 2017 Apr 8. PMID: 28400293; PMCID: PMC5581265.

Presenting Author

Morihiko Kawate

Poster Authors

Morihiko Kawate

MD

Keio University

Lead Author

E-mail

Saki Takaoka

MD

Department of Anesthesiology, Keio University School of Medicine

Lead Author

E-mail

Yuta Shinohara

MA

Interdisciplinary Pain Center, Keio University Hospital

Lead Author

E-mail

Chisato Tanaka

MD

Interdisciplinary Pain Center, Keio University Hospital

Lead Author

E-mail

Yihuan Wu M.D.

Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan

Lead Author

E-mail

Shizuko Kosugi M.D.

Ph.D.

Department of Anesthesiology, Keio University School of Medicine, Tokyo, Japan.

Lead Author

E-mail

Kenta Wakaizumi M.D.

Ph.D.

Department of Anesthesiology, Keio University School of Medicine

Lead Author

E-mail

Topics

  • Pain Imaging