DOI: 10.3724/SP.J.1042.2017.01758

Advances in Psychological Science (心理科学进展) 2017/25:10 PP.1758-1768

Neural mechanisms of pain-related fear and its reduction

Pain-related fear is an important topic in both basic and clinical research of pain. It is associated with pain hypervigilance and followed by avoidance behaviors, thereby resulting in the inaccurate processing of non-pain-related information, the disturbance of the body functions, as well as the exacerbation of pain disability. Individual pain-related fear can influence subjective pain perception and pain-related attention bias and avoidance behavior, as well as plays an important role in the development of chronic pain (e.g., chronic musculoskeletal pain) and the maintenance of physiological dysfunctions. Multiple cortical and sub-cortical brain regions, e.g., amygdala, hippocampus, dorsal anterior cingulate cortex, and prefrontal cortex, involve in the formation and expression of pain-related fear. Existing psychological-behavioral intervention therapies of reducing pain-related fear worked in different stages of pain-related fear formation (consolidation, reconsolidation, and extinction). Nevertheless, due to the complexity of pain-related fear formation and the influences of multiple factors, the effect of current psychological intervention therapies for reducing pain-related fear is not stable, yet there is a great gap between the relevant basic research and clinical applications. Differences of contexts in the formation of pain-related fear, as well as individual personality traits and psychological states, should be well taken into consideration in the future study, which will help reduce or even eliminate the disturbing pain-related fear, thus relieving and removing pain sufferings.

Key words:pain-related fear,reduction of pain-related fear,pain relief,psychological therapies

ReleaseDate:2017-11-17 09:48:04

胡理, 罗层, 陈军. (2015). ICD-11慢性疼痛分类. 中国疼痛医学杂志, 21, 486-488.

吕振勇, 纪晓蕾, 黄丽, Jackson T, 陈红. (2013). 疼痛恐惧对疼痛的影响及其认知机制. 心理科学进展, 21, 817-826.

杨鸿斌. (2015). 天敌气味诱发的先天性恐惧的神经环路基础探究(博士学位论文). 浙江大学.

余莉. (2009). 骨科病人术后伤口疼痛的护理. 临床和实验医学杂志, 8(7), 160.

袁广琪. (2010). 慢性疼痛对老年人的影响研究. 实用医技杂志, 17, 652-653.

赵厚德, 陶均, 郝智慧, 赵雪征, 尚昌连, 王捷, 王禄增. (2004). 实验动物疼痛评价的探讨. 中国比较医学杂志, 14(6), 385-386.

Antony, J. W., Gobel, E. W., O'Hare, J. K., Reber, P. J., & Paller, K. A. (2012). Cued memory reactivation during sleep influences skill learning. Nature Neuroscience, 15, 1114-1116.

Asmundson, G. J. G., & Hadjistavropoulos, H. D. (2007). Is high fear of pain associated with attentional biases for pain-related or general threat? A categorical reanalysis. The Journal of Pain, 8, 11-18.

Auchter, A., Cormack, L. K., Niv, Y., Gonzalez-Lima, F., & Monfils, M. H. (2017). Reconsolidation-extinction interactions in fear memory attenuation:The role of inter-trial interval variability. Frontiers in Behavioral Neuroscience, 11, 2.

Bendor, D., & Wilson, M. A. (2012). Biasing the content of hippocampal replay during sleep. Nature Neuroscience, 15, 1439-1444.

Blair, H. T., Schafe, G. E., Bauer, E. P., Rodrigues, S. M., & LeDoux, J. E. (2001). Synaptic plasticity in the lateral amygdala:A cellular hypothesis of fear conditioning. Learning & Memory, 8, 229-242.

Bukalo, O., Pinard, C. R., Silverstein, S., Brehm, C., Hartley, N. D., Whittle, N.,... Holmes, A. (2015). Prefrontal inputs to the amygdala instruct fear extinction memory formation. Science Advances, 1, e1500251.

Chan, W. Y. M., Leung, H. T., Westbrook, R. F., & McNally, G. P. (2010). Effects of recent exposure to a conditioned stimulus on extinction of Pavlovian fear conditioning. Learning & Memory, 17, 512-521.

Choi, D. S., Choi, D. Y., Whittington, R. A., & Nedeljković, S. S. (2007). Sudden amnesia resulting in pain relief:The relationship between memory and pain. PAIN, 132, 206-210.

Costanzi, M., Cannas, S., Saraulli, D., Rossi-Arnaud, C., & Cestari, V. (2011). Extinction after retrieval:Effects on the associative and nonassociative components of remote contextual fear memory. Learning & Memory, 18, 508-518.

Crombez, G., Eccleston, C., Baeyens, F., van Houdenhove, B., & van Den Broeck, A. (1999). Attention to chronic pain is dependent upon pain-related fear. Journal of Psychosomatic Research, 47, 403-410.

Crombez, G., Eccleston, C., van Damme, S., Vlaeyen, J. W. S., & Karoly, P. (2012). Fear-avoidance model of chronic pain:The next generation. The Clinical Journal of Pain, 28, 475-483.

Crombez, G., Viane, I., Eccleston, C., Devulder, J., & Goubert, L. (2013). Attention to pain and fear of pain in patients with chronic pain. Journal of Behavioral Medicine, 36, 371-378.

Dawson, A. P., Schluter, P. J., Hodges, P. W., Stewart, S., & Turner, C. (2011). Fear of movement, passive coping, manual handling, and severe or radiating pain increase the likelihood of sick leave due to low back pain. PAIN, 152, 1517-1524.

de Carvalho Myskiw, J., Benetti, F., & Izquierdo, I. (2013). Behavioral tagging of extinction learning. Proceedings of the National Academy of Sciences of the United States of America, 110, 1071-1076.

de Jong, J. R., Vlaeyen, J. W. S., Onghena, P., Cuypers, C., den Hollander, M., & Ruijgrok, J. (2005). Reduction of pain-related fear in complex regional pain syndrome type I:The application of graded exposure in vivo. PAIN, 116, 264-275.

de Jong, J. R., Vlaeyen, J. W. S., van Eijsden, M., Loo, C., & Onghena, P. (2012). Reduction of pain-related fear and increased function and participation in work-related upper extremity pain (WRUEP):Effects of exposure in vivo. PAIN, 153, 2109-2118.

Diekelmann, S., Büchel, C., Born, J., & Rasch, B. (2011). Labile or stable:Opposing consequences for memory when reactivated during waking and sleep. Nature Neuroscience, 14, 381-386.

Feinstein, J. S., Adolphs, R., Damasio, A., & Tranel, D. (2011). The human amygdala and the induction and experience of fear. Current Biology, 21, 34-38.

Fendt, M., & Fanselow, M. S. (1999). The neuroanatomical and neurochemical basis of conditioned fear. Neuroscience & Biobehavioral Reviews, 23, 743-760.

Godges, J. J., Anger, M. A., Zimmerman, G., & Delitto, A. (2008). Effects of education on return-to-work status for people with fear-avoidance beliefs and acute low back pain. Physical Therapy, 88, 231-239.

Godinho, F., Faillenot, I., Perchet, C., Frot, M., Magnin, M., & Garcia-Larrea, L. (2012). How the pain of others enhances our pain:Searching the cerebral correlates of 'compassional hyperalgesia'. European Journal of Pain, 16, 748-759.

Haggman, S. P., Sharpe, L. A., Nicholas, M. K., & Refshauge, K. M. (2010). Attentional biases toward sensory pain words in acute and chronic pain patients. The Journal of Pain, 11, 1136-1145.

Hartley, C. A., & Phelps, E. A. (2010). Changing fear:The neurocircuitry of emotion regulation. Neuropsychopharmacology, 35, 136-146.

Häuser, W., Wolfe, F., Henningsen, P., Schmutzer, G., Brähler, E., & Hinz, A. (2014). Untying chronic pain:Prevalence and societal burden of chronic pain stages in the general population-a cross-sectional survey. BMC Public Health, 14, 352.

Hauner, K. K., Howard, J. D., Zelano, C., & Gottfried, J. A. (2013). Stimulus-specific enhancement of fear extinction during slow-wave sleep. Nature Neuroscience, 16, 1553-1555.

He, J., Sun, H. Q., Li, S. X., Zhang, W. H., Shi, J., Ai, S. Z.,... Lu, L. (2015). Effect of conditioned stimulus exposure during slow wave sleep on fear memory extinction in humans. Sleep, 38, 423-431.

Heath, F. C., Jurkus, R., Bast, T., Pezze, M. A., Lee, J. L. C., Voigt, J. P., & Stevenson, C. W. (2015). Dopamine D1-like receptor signalling in the hippocampus and amygdala modulates the acquisition of contextual fear conditioning. Psychopharmacology, 232, 2619-2629.

Helsen, K., Vlaeyen, J. W. S., & Goubert, L. (2015). Indirect acquisition of pain-related fear:An experimental study of observational learning using coloured cold metal bars. PLoS One, 10, e0117236.

Hofmann, S. G. (2008). Cognitive processes during fear acquisition and extinction in animals and humans:Implications for exposure therapy of anxiety disorders. Clinical Psychology Review, 28, 199-210.

Ji, J. Z., & Maren, S. (2005). Electrolytic lesions of the dorsal hippocampus disrupt renewal of conditional fear after extinction. Learning & Memory, 12, 270-276.

Jordão, E. M. A., Onishi, B. K. A., & Xavier, G. F. (2015). Pre-training reversible inactivation of the basal amygdala (BA) disrupts contextual, but not auditory, fear conditioning, in rats. PLoS One, 10, e0125489.

Khatibi, A., Dehghani, M., Sharpe, L., Asmundson, G. J. G., & Pouretemad, H. (2009). Selective attention towards painful faces among chronic pain patients:Evidence from a modified version of the dot-probe. PAIN, 142, 42-47.

Krahé, C., Paloyelis, Y., Condon, H., Jenkinson, P. M., Williams, S. C. R., & Fotopoulou, A. (2015). Attachment style moderates partner presence effects on pain:A laser-evoked potentials study. Social Cognitive and Affective Neuroscience, 10, 1030-1037.

Kwapis, J. L., Jarome, T. J., & Helmstetter, F. J. (2015). The role of the medial prefrontal cortex in trace fear extinction. Learning & Memory, 22, 39-46.

Lang, P. J., Bradley, M. M., & Cuthbert, B. N. (1998). Emotion, motivation, and anxiety:Brain mechanisms and psychophysiology. Biological Psychiatry, 44, 1248-1263.

LeDoux, J. E., Cicchetti, P., Xagoraris, A., & Romanski, L. M. (1990). The lateral amygdaloid nucleus:Sensory interface of the amygdala in fear conditioning. The Journal of Neuroscience, 10, 1062-1069.

Liu, J. F., Zhao, L. Y., Xue, Y. X., Shi, J., Suo, L., Luo, Y. X.,... Lu, L. (2014). An unconditioned stimulus retrieval extinction procedure to prevent the return of fear memory. Biological Psychiatry, 76, 895-901.

Maren, S., & Chang, C. H. (2006). Recent fear is resistant to extinction. Proceedings of the National Academy of Sciences of the United States of America, 103, 18020-18025.

Marowsky, A., Yanagawa, Y., Obata, K., & Vogt, K. E. (2005). A specialized subclass of interneurons mediates dopaminergic facilitation of amygdala function. Neuron, 48, 1025-1037.

May, A. (2008). Chronic pain may change the structure of the brain. PAIN, 137, 7-15.

Meulders, A., Vansteenwegen, D., & Vlaeyen, J. W. S. (2012). Women, but not men, report increasingly more pain during repeated (un) predictable painful electrocutaneous stimulation:Evidence for mediation by fear of pain. PAIN, 153, 1030-1041.

Meulders, A., & Vlaeyen, J. W. S. (2013). The acquisition and generalization of cued and contextual pain-related fear:An experimental study using a voluntary movement paradigm. PAIN, 154, 272-282.

Milad, M. R., Quirk, G. J., Pitman, R. K., Orr, S. P., Fischl, B., & Rauch, S. L. (2007). A role for the human dorsal anterior cingulate cortex in fear expression. Biological Psychiatry, 62, 1191-1194.

Milad, M. R., & Quirk, G. J. (2012). Fear extinction as a model for translational neuroscience:Ten years of progress. Annual Review of Psychology, 63, 129-151.

Monfils, M. H., Cowansage, K. K., Klann, E., & LeDoux, J. E. (2009). Extinction-reconsolidation boundaries:Key to persistent attenuation of fear memories. Science, 324, 951-955.

Morton, D. B., & Griffiths, P. H. (1985). Guidelines on the recognition of pain, distress and discomfort in experimental animals and an hypothesis for assessment. The Veterinary Record, 116, 431-436.

Mørkved, N., Hartmann, K., Aarsheim, L. M., Holen, D., Milde, A. M., Bomyea, J., & Thorp, S. R. (2014). A comparison of narrative exposure therapy and prolonged exposure therapy for PTSD. Clinical Psychology Review, 34, 453-467.

Norrholm, S. D., Vervliet, B., Jovanovic, T., Boshoven, W., Myers, K. M., Davis, M.,... Duncan, E. J. (2008). Timing of extinction relative to acquisition:A parametric analysis of fear extinction in humans. Behavioral Neuroscience, 122, 1016-1030.

Orsini, C. A., & Maren, S. (2012). Neural and cellular mechanisms of fear and extinction memory formation. Neuroscience & Biobehavioral Reviews, 36, 1773-1802.

Pace-Schott, E. F., Germain, A., & Milad, M. R. (2015). Effects of sleep on memory for conditioned fear and fear extinction. Psychological Bulletin, 141, 835-857.

Peters, J., Dieppa-Perea, L. M., Melendez, L. M., & Quirk, G. J. (2010). Induction of fear extinction with hippocampal-infralimbic BDNF. Science, 328, 1288-1290.

Quirk, G. J., Likhtik, E., Pelletier, J. G., & Paré, D. (2003). Stimulation of medial prefrontal cortex decreases the responsiveness of central amygdala output neurons. The Journal of Neuroscience, 23, 8800-8807.

Quirk, G. J., Russo, G. K., Barron, J. L., & Lebron, K. (2000). The role of ventromedial prefrontal cortex in the recovery of extinguished fear. The Journal of Neuroscience, 20, 6225-6231.

Rao-Ruiz, P., Rotaru, D. C., van der Loo, R. J., Mansvelder, H. D., Stiedl, O., Smit, A. B., & Spijker, S. (2011). Retrieval-specific endocytosis of GluA2-AMPARs underlies adaptive reconsolidation of contextual fear. Nature Neuroscience, 14, 1302-1308.

Riecke, J., Holzapfel, S., Rief, W., & Glombiewski, J. A. (2013). Evaluation and implementation of graded in vivo exposure for chronic low back pain in a German outpatient setting:A study protocol of a randomized controlled trial. Trials, 14, 203.

Schiller, D., Kanen, J. W., LeDoux, J. E., Monfils, M. H., & Phelps, E. A. (2013). Extinction during reconsolidation of threat memory diminishes prefrontal cortex involvement. Proceedings of the National Academy of Sciences of the United States of America, 110, 20040-20045.

Schiller, D., Monfils, M. H., Raio, C. M., Johnson, D. C., LeDoux, J. E., & Phelps, E. A. (2010). Preventing the return of fear in humans using reconsolidation update mechanisms. Nature, 463, 49-53.

Schwabe, L., Nader, K., & Pruessner, J. C. (2014). Reconsolidation of human memory:Brain mechanisms and clinical relevance. Biological Psychiatry, 76, 274-280.

Simon, L. S. (2012). Relieving pain in America:A blueprint for transforming prevention, care, education, and research. Journal of Pain & Palliative Care Pharmacotherapy, 26, 197-198.

Traeger, A. C., Henschke, N., Hübscher, M., Williams, C. M., Kamper, S. J., Maher, C. G.,... & McAuley, J. H. (2016). Estimating the risk of chronic pain:Development and validation of a prognostic model (PICKUP) for patients with acute low back pain. PLoS Medicine, 13, e1002019.

Trivedi, M. A., & Coover, G. D. (2004). Lesions of the ventral hippocampus, but not the dorsal hippocampus, impair conditioned fear expression and inhibitory avoidance on the elevated T-maze. Neurobiology of Learning and Memory, 81, 172-184.

Tronson, N. C., & Taylor, J. R. (2007). Molecular mechanisms of memory reconsolidation. Nature Reviews Neuroscience, 8, 262-275.

Trost, Z., France, C. R., & Thomas, J. S. (2011). Pain-related fear and avoidance of physical exertion following delayed-onset muscle soreness. PAIN, 152, 1540-1547.

Trost, Z., France, C. R., Sullivan, M. J., & Thomas, J. S. (2012). Pain-related fear predicts reduced spinal motion following experimental back injury. PAIN, 153, 1015-1021.

Turk, D. C., Robinson, J. P., Sherman, J. J., Burwinkle, T., & Swanson, K. (2008). Assessing fear in patients with cervical pain:Development and validation of the pictorial fear of activity scale-cervical (PFActS-C). PAIN, 139, 55-62.

VanElzakker, M. B., Dahlgren, M. K., Davis, F. C., Dubois, S., & Shin, L. M. (2014). From Pavlov to PTSD:The extinction of conditioned fear in rodents, humans, and in anxiety disorders. Neurobiology of Learning and Memory, 113, 3-18.

Vidal-Gonzalez, I., Vidal-Gonzalez, B., Rauch, S. L., & Quirk, G. J. (2006). Microstimulation reveals opposing influences of prelimbic and infralimbic cortex on the expression of conditioned fear. Learning & Memory, 13, 728-733.

Vlaeyen, J. W. S., Hanssen, M., Goubert, L., Vervoort, T., Peters, M., van Breukelen, G.,... Morley, S. (2009). Threat of pain influences social context effects on verbal pain report and facial expression. Behaviour Research and Therapy, 47, 774-782.

Vlaeyen, J. W. S., & Linton, S. J. (2012). Fear-avoidance model of chronic musculoskeletal pain:12 years on. PAIN, 153, 1144-1147.

Volders, S., Boddez, Y., De Peuter, S., Meulders, A., & Vlaeyen, J. W. S. (2015). Avoidance behavior in chronic pain research:A cold case revisited. Behaviour Research and Therapy, 64, 31-37.

Vouimba, R. M., & Maroun, M. (2011). Learning-induced changes in mPFC-BLA connections after fear conditioning, extinction, and reinstatement of fear. Neuropsychopharmacology, 36, 2276-2285.

Wagner, U., Hallschmid, M., Rasch, B., & Born, J. (2006). Brief sleep after learning keeps emotional memories alive for years. Biological Psychiatry, 60, 788-790.

Whittaker, A. L., & Howarth, G. S. (2014). Use of spontaneous behaviour measures to assess pain in laboratory rats and mice:How are we progressing? Applied Animal Behaviour Science, 151, 1-12.

Xue, Y. X., Luo, Y. X., Wu, P., Shi, H. S., Xue, L. F., Chen, C.,... Lu, L. (2012). A memory retrieval-extinction procedure to prevent drug craving and relapse. Science, 336, 241-245.

Yang, Z., Jackson, T., Gao, X., & Chen, H. (2012). Identifying selective visual attention biases related to fear of pain by tracking eye movements within a dot-probe paradigm. PAIN, 153, 1742-1748.

Yehuda, R., & LeDoux, J. (2007). Response variation following trauma:A translational neuroscience approach to understanding PTSD. Neuron, 56, 19-32.

Zale, E. L., Lange, K. L., Fields, S. A., & Ditre, J. W. (2013). The relation between pain-related fear and disability:A meta-analysis. The Journal of Pain, 14, 1019-1030.