Abstract
Primary dysmenorrhea (PDM) is a cyclic menstrual pain in the absence of pelvic anomalies, and women with PDM have an increased sensitivity to pain than the internal and external areas associated with menstrual pain. However, the brain abnormality in the ascending pain pathways in dysmenorrhea remains largely unclear. As the thalamus plays a significant role in transmission of nociceptive input, we examined whether white matter microstructure of the thalamus-related fiber tracts obtained by DTI in women with PDM (n = 47) differs from healthy controls. A novel tractography atlas-based analysis method that detects tract integrity and altered microstructural properties along selected fibers was employed. The fiber bundles of interest contained the thalamus- primary somatosensory cortex (SI), thalamus- dorsal anterior cingulate cortex (dACC)/supplementary motor area (SMA), thalamus-insula, and thalamus-ACC. As compared with controls, abnormal white matter microstructures were found along the thalamus-related white matter fiber tracts. Additionally, the intensity of menstrual pain was significantly associated with diffusion measures of thalamus-SI fiber connections. Our study suggested that the thalamus-related pain processing pathways had altered white matter integrity that persisted beyond the time of menstruation, and the white matter microstructure of the thalamus-SI pathways was closely related to menstrual pain in the intensity by women with PDM.
This is a preview of subscription content, log in via an institution to check access.
Similar content being viewed by others
References
Akerlund, M. (2004). Vasopressin and oxytocin in normal reproduction and in the pathophysiology of preterm labour and primary dysmenorrhoea. Development of receptor antagonists for therapeutic use in these conditions. Roczniki Akademii Medycznej w Białymstoku, 49, 18–21.
Altman, G., Cain, K. C., Motzer, S., Jarrett, M., Burr, R., & Heitkemper, M. (2006). Increased symptoms in female IBS patients with dysmenorrhea and PMS. Gastroenterology Nursing, 29(1), 4–11. https://doi.org/10.1097/00001610-200601000-00002.
Apkarian, A. V., Bushnell, M. C., Treede, R. D., & Zubieta, J. K. (2005). Human brain mechanisms of pain perception and regulation in health and disease. European Journal of Pain, 9(4), 463–484. https://doi.org/10.1016/j.ejpain.2004.11.001.
Bajaj, P., Drewes, A. M., Gregersen, H., Petersen, P., Madsen, H., & Arendt-Nielsen, L. (2002). Controlled dilatation of the uterine cervix--an experimental visceral pain model. Pain, 99(3), 433–442. https://doi.org/10.1016/s0304-3959(02)00182-3.
Berkley, K. J., & McAllister, S. L. (2011). Don't dismiss dysmenorrhea! Pain, 152(9), 1940–1941. https://doi.org/10.1016/j.pain.2011.04.013.
Brinkert, W., Dimcevski, G., Arendt-Nielsen, L., Drewes, A. M., & Wilder-Smith, O. H. (2007). Dysmenorrhoea is associated with hypersensitivity in the sigmoid colon and rectum. Pain, 132(Suppl 1), S46–S51. https://doi.org/10.1016/j.pain.2006.12.011.
Chen, P. C., Chen, M. H., Chen, H. L., Lu, C. H., Chou, K. H., Wu, R. W., Tsai, N. W., Lin, C. P., Li, S. H., Chen, Y. W., Cheng, Y. F., & Lin, W. C. (2015). Callosal damage and cognitive deficits in chronic carbon monoxide intoxication: A diffusion tensor imaging study. Journal of the Neurological Sciences, 355(1–2), 101–107. https://doi.org/10.1016/j.jns.2015.05.030.
Chung, S. D., Liu, S. P., Lin, H. C., & Kang, J. H. (2014). Association of dysmenorrhea with interstitial cystitis/bladder pain syndrome: A case-control study. Acta Obstetricia et Gynecologica Scandinavica, 93(9), 921–925. https://doi.org/10.1111/aogs.12437.
Fornito, A., Zalesky, A., & Breakspear, M. (2015). The connectomics of brain disorders. Nature Reviews. Neuroscience, 16(3), 159–172. https://doi.org/10.1038/nrn3901.
Gauriau, C., & Bernard, J. F. (2004). Posterior triangular thalamic neurons convey nociceptive messages to the secondary somatosensory and insular cortices in the rat. The Journal of Neuroscience, 24(3), 752–761. https://doi.org/10.1523/jneurosci.3272-03.2004.
Geng, X., Gouttard, S., Sharma, A., Gu, H., Styner, M., Lin, W., Gerig, G., & Gilmore, J. H. (2012). Quantitative tract-based white matter development from birth to age 2years. Neuroimage, 61(3), 542–557. https://doi.org/10.1016/j.neuroimage.2012.03.057.
Giamberardino, M. A., Affaitati, G., Martelletti, P., Tana, C., Negro, A., Lapenna, D., Curto, M., Schiavone, C., Stellin, L., Cipollone, F., & Costantini, R. (2015). Impact of migraine on fibromyalgia symptoms. The Journal of Headache and Pain, 17, 28. https://doi.org/10.1186/s10194-016-0619-8.
Giamberardino, M. A., Berkley, K. J., Iezzi, S., de Bigontina, P., & Vecchiet, L. (1997). Pain threshold variations in somatic wall tissues as a function of menstrual cycle, segmental site and tissue depth in non-dysmenorrheic women, dysmenorrheic women and men. Pain, 71(2), 187–197. https://doi.org/10.1016/s0304-3959(97)03362-9.
Goodlett, C. B., Fletcher, P. T., Gilmore, J. H., & Gerig, G. (2009). Group analysis of DTI fiber tract statistics with application to neurodevelopment. Neuroimage, 45(1 Suppl), S133–S142. https://doi.org/10.1016/j.neuroimage.2008.10.060.
Granot, M., Yarnitsky, D., Itskovitz-Eldor, J., Granovsky, Y., Peer, E., & Zimmer, E. Z. (2001). Pain perception in women with dysmenorrhea. Obstetrics and Gynecology, 98(3), 407–411. https://doi.org/10.1016/s0029-7844(01)01465-x.
Gupta, A., Rapkin, A. J., Gill, Z., Kilpatrick, L., Fling, C., Stains, J., Masghati, S., Tillisch, K., Mayer, E. A., & Labus, J. S. (2015). Disease-related differences in resting-state networks: A comparison between localized provoked vulvodynia, irritable bowel syndrome, and healthy control subjects. Pain, 156(5), 809–819. https://doi.org/10.1097/01.j.pain.0000461289.65571.54.
Han, F., Liu, H., Wang, K., Yang, J., Yang, L., Liu, J., Zhang, M., & Dun, W. (2019). Correlation between thalamus-related functional connectivity and serum BDNF levels during the Periovulatory phase of primary dysmenorrhea. Frontiers in Human Neuroscience, 13, 333. https://doi.org/10.3389/fnhum.2019.00333.
Hellman, K. M., Datta, A., Steiner, N. D., Kane Morlock, J. N., Garrison, E. F., Clauw, D. J., et al. (2018). Identification of experimental bladder sensitivity among dysmenorrhea sufferers. Am J Obstet Gynecol, 219(1), 84.e81–84.e88. https://doi.org/10.1016/j.ajog.2018.04.030.
Hellman, K. M., Roth, G. E., Dillane, K. E., Garrison, E. F., Oladosu, F. A., Clauw, D. J., & Tu, F. F. (2020). Dysmenorrhea subtypes exhibit differential quantitative sensory assessment profiles. Pain, 161, 1227–1236. https://doi.org/10.1097/j.pain.0000000000001826.
Hodges, P. W., & Tucker, K. (2011). Moving differently in pain: A new theory to explain the adaptation to pain. Pain, 152(3 Suppl), S90–S98. https://doi.org/10.1016/j.pain.2010.10.020.
Iacovides, S., Avidon, I., Bentley, A., & Baker, F. C. (2014). Reduced quality of life when experiencing menstrual pain in women with primary dysmenorrhea. Acta Obstetricia et Gynecologica Scandinavica, 93(2), 213–217. https://doi.org/10.1111/aogs.12287.
Ju, H., Jones, M., & Mishra, G. D. (2014). Premenstrual syndrome and dysmenorrhea: Symptom trajectories over 13 years in young adults. Maturitas, 78(2), 99–105. https://doi.org/10.1016/j.maturitas.2014.03.008.
Kilpatrick, L. A., Kutch, J. J., Tillisch, K., Naliboff, B. D., Labus, J. S., Jiang, Z., Farmer, M. A., Apkarian, A. V., Mackey, S., Martucci, K. T., Clauw, D. J., Harris, R. E., Deutsch, G., Ness, T. J., Yang, C. C., Maravilla, K., Mullins, C., & Mayer, E. A. (2014). Alterations in resting state oscillations and connectivity in sensory and motor networks in women with interstitial cystitis/painful bladder syndrome. The Journal of Urology, 192(3), 947–955. https://doi.org/10.1016/j.juro.2014.03.093.
Kim, S. S., Gomez-Ramirez, M., Thakur, P. H., & Hsiao, S. S. (2015). Multimodal interactions between proprioceptive and cutaneous signals in primary somatosensory cortex. Neuron, 86(2), 555–566. https://doi.org/10.1016/j.neuron.2015.03.020.
Kutch, J. J., & Tu, F. F. (2016). Altered brain connectivity in dysmenorrhea: Pain modulation and the motor cortex. Pain, 157(1), 5–6. https://doi.org/10.1097/j.pain.0000000000000364.
Kutch, J. J., Yani, M. S., Asavasopon, S., Kirages, D. J., Rana, M., Cosand, L., Labus, J. S., Kilpatrick, L. A., Ashe-McNalley, C., Farmer, M. A., Johnson, K. A., Ness, T. J., Deutsch, G., Harris, R. E., Apkarian, A. V., Clauw, D. J., Mackey, S. C., Mullins, C., & Mayer, E. A. (2015). Altered resting state neuromotor connectivity in men with chronic prostatitis/chronic pelvic pain syndrome: A MAPP: Research network neuroimaging study. Neuroimage Clin, 8, 493–502. https://doi.org/10.1016/j.nicl.2015.05.013.
Leemans, A., & Jones, D. K. (2009). The B-matrix must be rotated when correcting for subject motion in DTI data. Magnetic Resonance in Medicine, 61(6), 1336–1349. https://doi.org/10.1002/mrm.21890.
Li, W. C., Tu, C. H., Chao, H. T., Yeh, T. C., Chen, L. F., & Hsieh, J. C. (2015). High prevalence of incidental brain findings in primary dysmenorrhoea. European Journal of Pain, 19(8), 1071–1074. https://doi.org/10.1002/ejp.639.
Liu, J., Liu, H., Mu, J., Xu, Q., Chen, T., Dun, W., Yang, J., Tian, J., Hu, L., & Zhang, M. (2017a). Altered white matter microarchitecture in the cingulum bundle in women with primary dysmenorrhea: A tract-based analysis study. Human Brain Mapping, 38(9), 4430–4443.
Liu, P., Liu, Y., Wang, G., Yang, X., Jin, L., Sun, J., & Qin, W. (2017b). Aberrant default mode network in patients with primary dysmenorrhea: A fMRI study. Brain Imaging and Behavior, 11(5), 1479–1485. https://doi.org/10.1007/s11682-016-9627-1.
Liu, P., Yang, J., Wang, G., Liu, Y., Liu, X., Jin, L., Liang, F., Qin, W., & Calhoun, V. D. (2016). Altered regional cortical thickness and subcortical volume in women with primary dysmenorrhoea. European Journal of Pain, 20(4), 512–520. https://doi.org/10.1002/ejp.753.
Lundstrom, V., & Green, K. (1978). Endogenous levels of prostaglandin F2alpha and its main metabolites in plasma and endometrium of normal and dysmenorrheic women. American Journal of Obstetrics and Gynecology, 130(6), 640–646. https://doi.org/10.1016/0002-9378(78)90320-4.
Mansour, A. R., Baliki, M. N., Huang, L., Torbey, S., Herrmann, K. M., Schnitzer, T. J., & Apkarian, V. A. (2013). Brain white matter structural properties predict transition to chronic pain. Pain, 154(10), 2160–2168. https://doi.org/10.1016/j.pain.2013.06.044.
Moulton, E. A., Keaser, M. L., Gullapalli, R. P., & Greenspan, J. D. (2005). Regional intensive and temporal patterns of functional MRI activation distinguishing noxious and innocuous contact heat. Journal of Neurophysiology, 93(4), 2183–2193.
O'Donnell, L. J., Westin, C. F., & Golby, A. J. (2009). Tract-based morphometry for white matter group analysis. Neuroimage, 45(3), 832–844. https://doi.org/10.1016/j.neuroimage.2008.12.023.
Simons, S. B., Chiu, J., Favorov, O. V., Whitsel, B. L., & Tommerdahl, M. (2007). Duration-dependent response of SI to vibrotactile stimulation in squirrel monkey. Journal of Neurophysiology, 97(3), 2121–2129. https://doi.org/10.1152/jn.00513.2006.
Todd, A. J. (2010). Neuronal circuitry for pain processing in the dorsal horn. Nature Reviews. Neuroscience, 11(12), 823–836. https://doi.org/10.1038/nrn2947.
Tommerdahl, M., Favorov, O. V., & Whitsel, B. L. (2010). Dynamic representations of the somatosensory cortex. Neuroscience and Biobehavioral Reviews, 34(2), 160–170. https://doi.org/10.1016/j.neubiorev.2009.08.009.
Tu, C. H., Niddam, D. M., Chao, H. T., Chen, L. F., Chen, Y. S., Wu, Y. T., Yeh, T. C., Lirng, J. F., & Hsieh, J. C. (2010). Brain morphological changes associated with cyclic menstrual pain. Pain, 150(3), 462–468.
Tu, C. H., Niddam, D. M., Chao, H. T., Liu, R. S., Hwang, R. J., Yeh, T. C., & Hsieh, J. C. (2009). Abnormal cerebral metabolism during menstrual pain in primary dysmenorrhea. Neuroimage, 47(1), 28–35. https://doi.org/10.1016/j.neuroimage.2009.03.080.
Tu, C. H., Niddam, D. M., Yeh, T. C., Lirng, J. F., Cheng, C. M., Chou, C. C., Chao, H. T., & Hsieh, J. C. (2013). Menstrual pain is associated with rapid structural alterations in the brain. Pain, 154(9), 1718–1724. https://doi.org/10.1016/j.pain.2013.05.022.
Vecchiet, L., Vecchiet, J., & Giamberardino, M. A. (1999). Referred muscle pain: Clinical and pathophysiologic aspects. Current Review of Pain, 3(6), 489–498. https://doi.org/10.1007/s11916-999-0077-y.
Vierck, C. J., Whitsel, B. L., Favorov, O. V., Brown, A. W., & Tommerdahl, M. (2013). Role of primary somatosensory cortex in the coding of pain. Pain, 154(3), 334–344. https://doi.org/10.1016/j.pain.2012.10.021.
Vincent, K. (2011). Pelvic pain in women: Clinical and scientific aspects. Current Opinion in Supportive and Palliative Care, 5(2), 143–149. https://doi.org/10.1097/SPC.0b013e3283460b05.
Whitsel, B. L., Favorov, O. V., Li, Y., Lee, J., Quibrera, P. M., & Tommerdahl, M. (2010). Nociceptive afferent activity alters the SI RA neuron response to mechanical skin stimulation. Cerebral Cortex, 20(12), 2900–2915. https://doi.org/10.1093/cercor/bhq039.
Willis, W. D., & Westlund, K. N. (1997). Neuroanatomy of the pain system and of the pathways that modulate pain. Journal of Clinical Neurophysiology, 14(1), 2–31.
Zhang, X., Kostarczyk, E., & Giesler Jr., G. J. (1995). Spinohypothalamic tract neurons in the cervical enlargement of rats: Descending axons in the ipsilateral brain. The Journal of Neuroscience, 15(12), 8393–8407.
Zhuo, M. (2016). Contribution of synaptic plasticity in the insular cortex to chronic pain. Neuroscience, 338, 220–229.
Zung, W. W. (1965). A self-rating depression scale. Archives of General Psychiatry, 12, 63–70. https://doi.org/10.1001/archpsyc.1965.01720310065008.
Zung, W. W. (1971). A rating instrument for anxiety disorders. Psychosomatics, 12(6), 371–379. https://doi.org/10.1016/s0033-3182(71)71479-0.
Acknowledgments
This work was supported by the National Natural Science Foundation of China (Grant Nos. 81901723, 81871331, and 81871330), the National Natural Science Foundation of Shaanxi Province (Grant No. 2018JM7127), the Fundamental Research Funds for Central Universities (Grant No. xjj2018261) and the Institutional Science Foundation of First Affiliated Hospital of Xi’an Jiaotong University (Grant No. 2017QN-24).
Author information
Authors and Affiliations
Corresponding authors
Ethics declarations
Conflict of interest
Juan He, Wanghuan Dun, Fang Han, Ke Wang, Jing Yang, Shaohui Ma and Ming Zhang critically reviewed the content and approved the final version for publication. They declared no conflict of interest.
Ethical approval
All procedures performed in studies involving human participants were in accordance with the ethical standards of institutional and/or national research committee and with the 1964 Helsinki declaration and its later amendments or comparable ethical standards.
Ethical statements
Informed consent was obtained from all individual participants included in the study.
Additional information
Publisher’s note
Springer Nature remains neutral with regard to jurisdictional claims in published maps and institutional affiliations.
Electronic supplementary material
ESM 1
(DOCX 384 kb)
Rights and permissions
About this article
Cite this article
He, J., Dun, W., Han, F. et al. Abnormal white matter microstructure along the thalamus fiber pathways in women with primary dysmenorrhea. Brain Imaging and Behavior 15, 2061–2068 (2021). https://doi.org/10.1007/s11682-020-00400-9
Accepted:
Published:
Issue Date:
DOI: https://doi.org/10.1007/s11682-020-00400-9