Altered Endogenous Pain-Inhibitory Function in Older Adults With Chronic Pain Is Associated With Disruptions in Functional Connectivity During Resting State.
Dorado, Alejandro; Terrasa, Juan Lorenzo; VAN DER MEULEN, Marianet al.
[en] Increasing research points to a decline in the ability to internally regulate pain as a contributing factor to the increased pain susceptibility in aging. This study investigated the connection between pain regulation and resting-state functional connectivity (rsFC) in older adults with chronic pain. We compared functional magnetic resonance imaging rsFC of 30 older adults with chronic pain (69.5 ± 6.58 years, 14 males), 29 pain-free older (70.48 ± 4.60, 15 males), and 30 younger adults (20.0 ± 1.58, 15 males). Pain inhibition and facilitatory capabilities were assessed using conditioned pain modulation (CPM) and temporal summation. Older adults with chronic pain displayed lower pain inhibition during the CPM than pain-free older and younger adults. rsFC analysis showed that older adults with chronic pain, in comparison with younger participants, displayed an abnormal hyperconnectivity between right dorsolateral prefrontal cortex and left amygdala, which was significantly correlated with lower pain inhibition during the CPM. Older adults with chronic pain displayed higher connectivity between the primary somatosensory cortex and nucleus accumbens than pain-free older adults. Finally, both older adult groups displayed reduced connectivity between brain structures involved in pain inhibition and processing in comparison with younger adults. Altogether, our results suggest that suffering from pain during aging leads to a dysfunction of pain-inhibitory processes, which significantly surpass those caused by normal aging. Furthermore, our results point to a key role of emotional and motivational brain areas, and their interaction with executive and somatosensory areas, in the reduced inhibitory capacity and likely the maintenance of chronic pain in aging. PERSPECTIVE: This study examines the link between reduced pain-inhibition capacity and increased resting-state connectivity between affective, sensory, and executive brain structures in older adults with chronic pain. These findings could inform new pain assessment and treatment programs for this population.
Disciplines :
Neurosciences & behavior
Author, co-author :
Dorado, Alejandro ; Cognitive and Affective Neuroscience and Clinical Psychology, Research Institute of Health Sciences (IUNICS) and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands (UIB), Palma, Spain
Terrasa, Juan Lorenzo; Cognitive and Affective Neuroscience and Clinical Psychology, Research Institute of Health Sciences (IUNICS) and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands (UIB), Palma, Spain
Montoya, Pedro; Cognitive and Affective Neuroscience and Clinical Psychology, Research Institute of Health Sciences (IUNICS) and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands (UIB), Palma, Spain
González-Roldán, Ana María; Cognitive and Affective Neuroscience and Clinical Psychology, Research Institute of Health Sciences (IUNICS) and Balearic Islands Health Research Institute (IdISBa), University of the Balearic Islands (UIB), Palma, Spain. Electronic address: anamaria.gonzalez@uib.es
External co-authors :
yes
Language :
English
Title :
Altered Endogenous Pain-Inhibitory Function in Older Adults With Chronic Pain Is Associated With Disruptions in Functional Connectivity During Resting State.
Gobierno de España Ministerio de Ciencia e Innovación
Funding text :
The authors want to thank Fernand Anton for his assistance during the construction of the CPM paradigm, Sandra Rodr\u00EDguez-Alegre and Marta Delgado-Bitata for their help during fMRI sessions, and finally, the Son Dameto, Pere Garau, and Son Forteza Neighborhood Associations for their collaboration and assistance during participant recruitment.This work was supported by the Spanish Ministry of Science and Innovation (PID2019-110096GB-I00, PRE2020-092706) financed by MCIN/AEI /10.13039/501100011033. All authors declare that they have no conflicts of interest. Author acknowledges that this is not a preregistered study.
Domenichiello, A.F., Ramsden, C.E., The silent epidemic of chronic pain in older adults. Prog Neuropsychopharmacol Biol Psychiatry 93 (2019), 284–290.
Hackett, J., Naugle, K.E., Naugle, K.M., The decline of endogenous pain modulation with aging: a meta-analysis of temporal summation and conditioned pain modulation. J Pain 21 (2020), 514–528.
Bulls, H.W., Goodin, B.R., McNew, M., Gossett, E.W., Bradley, L.A., Minority aging and endogenous pain facilitatory processes. Pain Med 17 (2016), 1037–1048.
Farrell, M., Gibson, S., Age interacts with stimulus frequency in the temporal summation of pain. Pain Med 8 (2007), 514–520.
Yarnitsky, D., Role of endogenous pain modulation in chronic pain mechanisms and treatment. Pain 156 (2015), S24–S31.
Staud, R., Abnormal endogenous pain modulation is a shared characteristic of many chronic pain conditions. Expert Rev Neurother 12 (2012), 577–585.
O'Brien, A.T., Deitos, A., Triñanes Pego, Y., Fregni, F., Carrillo-de-la-Peña, M.T., Defective endogenous pain modulation in fibromyalgia: a meta-analysis of temporal summation and conditioned pain modulation paradigms. J Pain 19 (2018), 819–836.
Yu, G.Z., Ly, M., Karim, H.T., Muppidi, N., Aizenstein, H.J., Ibinson, J.W., Accelerated brain aging in chronic low back pain. Brain Res, 1755, 2021, 147263.
Cruz-Almeida, Y., Fillingim, R.B., Riley, J.L., et al. Chronic pain is associated with a brain aging biomarker in community-dwelling older adults. Pain 160 (2019), 1119–1130.
Bannister, K., Physiol, A.D., The plasticity of descending controls in pain: translational probing. J Physiol 595 (2017), 4159–4166.
Harrison, R., Gandhi, W., Van Reekum, C.M., Salomons, T.V., Conditioned pain modulation is associated with heightened connectivity between the periaqueductal grey and cortical regions. Pain Rep, 7, 2022, e999.
Farrell, M.J., Age-related changes in the structure and function of brain regions involved in pain processing. Pain Med 13 (2012), 37–43.
May, A., Chronic pain may change the structure of the brain. Pain 137 (2008), 7–15.
Cifre, I., Sitges, C., Fraiman, D., et al. Disrupted functional connectivity of the pain network in fibromyalgia. Psychosom Med 74 (2012), 55–62.
Lamichhane, B., Jayasekera, D., Jakes, R., Ray, W.Z., Leuthardt, E.C., Hawasli, A.H., Functional disruptions of the brain in low back pain: a potential imaging biomarker of functional disability. Front Neurol, 12, 2021, 669076.
González-Roldán, A.M., Terrasa, J.L., Sitges, C., van der Meulen, M., Anton, F., Montoya, P., Age-related changes in pain perception are associated with altered functional connectivity during resting state. Front Aging Neurosci, 12, 2020, 116.
Monroe, T.B., Fillingim, R.B., Bruehl, S.P., et al. Sex differences in brain regions modulating pain among older adults: a cross-sectional resting state functional connectivity study. Pain Med 19 (2018), 1737–1747.
Duke Han, S., Buchman, A.S., Arfanakis, K., Fleischman, D.A., Bennett, D.A., Functional connectivity networks associated with chronic musculoskeletal pain in old age. Int J Geriatr Psychiatry 28 (2013), 858–867.
Baran, T.M., Lin, F.V., Geha, P., Functional brain mapping in patients with chronic back pain shows age-related differences. Pain 163 (2022), E917–E926.
García-Campayo, J., Zamorano, E., Ruiz, M.A., et al. Cultural adaptation into Spanish of the generalized anxiety disorder-7 (GAD-7) scale as a screening tool. Health Qual Life Outcomes 8 (2010), 1–11.
Gómez-Gómez, I., Benítez, I., Bellón, J., et al. Utility of PHQ-2, PHQ-8 and PHQ-9 for detecting major depression in primary health care: a validation study in Spain. Psychol Med 53 (2023), 5625–5635.
de Andrés Ares, J., Cruces Prado, L.M., Canos Verdecho, M.A., et al. Validation of the Short Form of the Brief Pain Inventory (BPI-SF) in Spanish patients with non-cancer-related pain. Pain Pract 15 (2015), 643–653.
Lobo, A., Saz, P., Marcos, G., et al. Revalidation and standardization of the cognition mini-exam (first Spanish version of the Mini-Mental Status Examination) in the general geriatric population. Med Clin 112 (1999), 767–774.
Nicholas, M., Vlaeyen, J.W.S., Rief, W., et al. The IASP classification of chronic pain for ICD-11: chronic primary pain. Pain 160 (2019), 28–37.
Watson, D., Clark, L.A., Tellegen, A., Development and validation of brief measures of positive and negative affect: the PANAS scales. J Pers Soc Psychol 54 (1988), 1063–1070.
Esteve, R., Ramírez-Maestre, C., López-Martínez, A.E., Empirical evidence of the validity of the spanish version of the pain vigilance awareness questionnaire. Int J Behav Med 20 (2013), 59–68.
Solé, E., Castarlenas, E., Sánchez-Rodríguez, E., et al. The reliability and validity of the Spanish version of the Fear of Pain Questionnaire. J Health Psychol 24 (2019), 1134–1144.
Arendt-Nielsen, L., Brennum, J., Sindrup, S., Bak, P., Applied physiology of temporal summation in the human nociceptive system. Eur J Appl Physiol 68 (1994), 266–273.
Inui, K., Tran, T.D., Hoshiyama, M., Kakigi, R., Preferential stimulation of Aδ fibers by intra-epidermal needle electrode in humans. Pain 96 (2002), 247–252.
Zabala Mata, J., Lascurain-Aguirrebeña, I., Dominguez López, E., Azkue, J.J., Enhanced pronociceptive and disrupted antinociceptive mechanisms in nonspecific chronic neck pain. Phys Ther, 101, 2021, 223.
Naugle, K.M., Ohlman, T., Wind, B., Miller, L., Test-retest instability of temporal summation and conditioned pain modulation measures in older adults. Pain Med 21 (2020), 2863–2876.
Bossmann, T., Brauner, T., Lowak, H., Anton, F., Forster, C., Horstmann, T., Reliability of conditioned pain modulation for the assessment of endogenous pain control pathways. Neurol Psychiatry Brain Res 22 (2016), 155–161.
Lewis, G.N., Rice, D.A., McNair, P.J., Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis. J Pain 13 (2012), 936–944.
Yarnitsky, D., Conditioned pain modulation (the diffuse noxious inhibitory control-like effect): its relevance for acute and chronic pain states. Curr Opin Anaesthesiol 23 (2010), 611–615.
Whitfield-Gabrieli, S., Nieto-Castanon, A., Conn: a functional connectivity toolbox for correlated and anticorrelated brain networks. Brain Connect 2 (2012), 125–141.
Desikan, R.S., Ségonne, F., Fischl, B., et al. An automated labeling system for subdividing the human cerebral cortex on MRI scans into gyral based regions of interest. Neuroimage 31 (2006), 968–980.
Coulombe, M.A., Lawrence, K.S., Moulin, D.E., et al. Lower functional connectivity of the periaqueductal gray is related to negative affect and clinical manifestations of fibromyalgia. Front Neuroanat, 11, 2017, 47.
MacDonald, P.L., Gardner, R.C., Type I error rate comparisons of post hoc procedures for I × J chi-square tables. Educ Psychol Meas 60 (2000), 735–754.
Sharpe, D., Chi-square test is statistically significant: now what?. Pract Assess Res Eval, 20, 2015, 8.
Wiesenfeld-Hallin, Z., Sex differences in pain perception. Gend Med 2 (2005), 137–145.
Lautenbacher, S., Kunz, M., Strate, P., Nielsen, J., Arendt-Nielsen, L., Age effects on pain tresholds, temporal summation and spatial summation of heat and pressure pain. Pain 115 (2005), 410–418.
Marouf, R., Piche, M., Rainville, P., Is temporal summation of pain and spinal nociception altered during normal aging?. Pain 156 (2015), 1945–1953.
Lim, M., Roosink, M., Kim, J.S., et al. Augmented pain processing in primary and secondary somatosensory cortex in fibromyalgia: a magnetoencephalography study using intra-epidermal electrical stimulation. PLoS One, 11, 2016, 0151776.
Mylius, V., Kunz, M., Hennighausen, E., Lautenbacher, S., Schepelmann, K., Effects of ageing on spinal motor and autonomic pain responses. Neurosci Lett 446 (2008), 129–132.
Baliki, M.N., Petre, B., Torbey, S., et al. Corticostriatal functional connectivity predicts transition to chronic back pain. Nat Neurosci 15 (2012), 1117–1119.
Baliki, M.N., Geha, P.Y., Fields, H.L., Apkarian, A.V., Predicting value of pain and analgesia: nucleus accumbens response to noxious stimuli changes in the presence of chronic pain. Neuron 66 (2010), 149–160.
Apkarian, A., Baliki, M.N., Farmer, M.A., Predicting transition to chronic pain. Curr Opin Neurol 26 (2013), 360–367.
Levy, D.J., Glimcher, P.W., The root of all value: a neural common currency for choice. Curr Opin Neurobiol 22 (2012), 1027–1038.
Mogenson, G.J., Jones, D.L., Yim, C.Y., From motivation to action: functional interface between the limbic system and the motor system. Prog Neurobiol 14 (1980), 69–97.
Ziółkowska, B., The role of mesostriatal dopamine system and corticostriatal glutamatergic transmission in chronic pain. Brain Sci, 11, 2021, 1311.
Ren, W., Centeno, M.V., Berger, S., et al. The indirect pathway of the nucleus accumbens shell amplifies neuropathic pain. Nat Neurosci, 19(2), 2016, 220.
Makary, M.M., Polosecki, P., Cecchi, G.A., et al. Loss of nucleus accumbens low-frequency fluctuations is a signature of chronic pain. PNAS 117 (2020), 10015–10023.
Tracey, I., Mantyh, P.W., The cerebral signature for pain perception and its modulation. Neuron 55 (2007), 377–391.
Basbaum, A.I., Fields, H.L., Endogenous pain control systems: brainstem spinal pathways and endorphin circuitry. Annu Rev Neurosci 7 (1984), 309–338.
Thompson, J.M., Neugebauer, V., Amygdala plasticity and pain. Pain Res Manag, 1, 2017, 8296501.
Bushnell, M.C., Čeko, M., Low, L.A., Cognitive and emotional control of pain and its disruption in chronic pain. Nat Rev Neurosci 14 (2013), 502–511.
Ji, G., Sun, H., Fu, Y., et al. Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation. J Neurosci 30 (2010), 5451–5464.
Terrasa, J.L., Montoya, P., Sitges, C., van der Meulen, M., Anton, F., González-Roldán, A.M., Anterior cingulate cortex activity during rest is related to alterations in pain perception in aging. Front Aging Neurosci, 13, 2021, 695200.
