Phantom limb pain after unilateral arm amputation is associated with decreased heat pain thresholds in the face.
Journal
European journal of pain (London, England)
ISSN: 1532-2149
Titre abrégé: Eur J Pain
Pays: England
ID NLM: 9801774
Informations de publication
Date de publication:
01 2022
01 2022
Historique:
pubmed:
22
7
2021
medline:
5
3
2022
entrez:
21
7
2021
Statut:
ppublish
Résumé
The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes. In this study, we applied QST in 37 unilateral upper-limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth. We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP. We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms. Phantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.
Sections du résumé
BACKGROUND
The mechanisms underlying chronic phantom limb pain (PLP) are complex and insufficiently understood. Altered sensory thresholds are often associated with chronic pain but quantitative sensory testing (QST) in PLP has so far been inconclusive due to large methodological variation between studies and small sample sizes.
METHODS
In this study, we applied QST in 37 unilateral upper-limb amputees (23 with and 14 without PLP) and 19 healthy controls. We assessed heat pain (HPT), pressure pain, warmth detection and two-point discrimination thresholds at the residual limb, a homologous point and the thenar of the intact limb as well as both corners of the mouth.
RESULTS
We did not find significant differences in any of the thresholds between the groups. However, PLP intensity was negatively associated with HPT at all measured body sites except for the residual limb, indicating lower pain thresholds with higher PLP levels. Correlations between HPT and PLP were strongest in the contralateral face (r = -0.65, p < 0.001). Facial HPT were specifically associated with PLP, independent of residual limb pain (RLP) and various other covariates. HPT at the residual limb, however, were significantly associated with RLP, but not with PLP.
CONCLUSION
We conclude that the association between PLP and, especially facial, HPT could be related to central mechanisms.
SIGNIFICANCE
Phantom limb pain (PLP) is still poorly understood. We show that PLP intensity is associated with lower heat pain thresholds, especially in the face. This finding could be related to central nervous changes in PLP.
Types de publication
Journal Article
Research Support, Non-U.S. Gov't
Langues
eng
Sous-ensembles de citation
IM
Pagination
114-132Informations de copyright
© 2021 The Authors. European Journal of Pain published by John Wiley & Sons Ltd on behalf of European Pain Federation - EFIC ®.
Références
Akatsuka, K., Noguchi, Y., Harada, T., Sadato, N., & Kakigi, R. (2008). Neural codes for somatosensory two-point discrimination in inferior parietal lobule: An fMRI study. NeuroImage, 40(2), 852-858. https://doi.org/10.1016/j.neuroimage.2007.12.013
Apkarian, A. V., Baliki, M. N., & Farmer, M. A. (2013). Predicting transition to chronic pain. Current Opinion in Neurology, 26(4), 360-367. https://doi.org/10.1097/WCO.0b013e32836336ad
Bates, D., Mächler, M., Bolker, B., & Walker, S. (2014). Fitting linear mixed-effects models using lme4. ArXiv Preprint arXiv:1406.5823.
Bekrater-Bodmann, R., Chung, B. Y., Richter, I., Wicking, M., Foell, J., Mancke, F., Schmahl, C., & Flor, H. (2015). Deficits in pain perception in borderline personality disorder: Results from the thermal grill illusion. Pain, 156(10), 2084-2092. https://doi.org/10.1097/j.pain.0000000000000275
Bekrater-Bodmann, R., Schredl, M., Diers, M., Reinhard, I., Foell, J., Trojan, J., Fuchs, X., & Flor, H. (2015). Post-amputation pain is associated with the recall of an impaired body representation in dreams-results from a nation-wide survey on limb amputees. PLoS One, 10(3), e0119552. https://doi.org/10.1371/journal.pone.0119552
Benjamini, Y., & Hochberg, Y. (1995). Controlling the false discovery rate: A practical and powerful approach to multiple testing. Journal of the Royal Statistical Society. Series B (Methodological), 57(1), 289-300. https://doi.org/10.2307/2346101
Bonzano, L., Tacchino, A., Roccatagliata, L., Abbruzzese, G., Mancardi, G. L., & Bove, M. (2008). Callosal contributions to simultaneous bimanual finger movements. The Journal of Neuroscience, 28(12), 3227-3233. https://doi.org/10.1523/JNEUROSCI.4076-07.2008
Catley, M. J., O’Connell, N. E., Berryman, C., Ayhan, F. F., & Moseley, G. L. (2014). Is tactile acuity altered in people with chronic pain? A systematic review and meta-analysis. The Journal of Pain, 15(10), 985-1000. https://doi.org/10.1016/j.jpain.2014.06.009
Cronholm, B. (1951). Phantom limbs in amputees; a study of changes in the integration of centripetal impulses with special reference to referred sensations. Acta Psychiatrica Et Neurologica Scandinavica Supplementum, 72, 1-310.
Davis, K. D., Kucyi, A., & Moayedi, M. (2015). The pain switch: An “ouch” detector. Pain, 156(11), 2164-2166. https://doi.org/10.1097/j.pain.0000000000000303
Davis, K. D., & Moayedi, M. (2013). Central mechanisms of pain revealed through functional and structural MRI. Journal of Neuroimmune Pharmacology, 8(3), 518-534. https://doi.org/10.1007/s11481-012-9386-8
Devor, M. (1991). Neuropathic pain and injured nerve: Peripheral mechanisms. British Medical Bulletin, 47(3), 619-630. https://doi.org/10.1093/oxfordjournals.bmb.a072496
Di Pietro, F., McAuley, J. H., Parkitny, L., Lotze, M., Wand, B. M., Moseley, G. L., & Stanton, T. R. (2013). Primary somatosensory cortex function in complex regional pain syndrome: A systematic review and meta-analysis. The Journal of Pain, 14(10), 1001-1018. https://doi.org/10.1016/j.jpain.2013.04.001
Dietrich, C., Walter-Walsh, K., Preißler, S., Hofmann, G. O., Witte, O. W., Miltner, W. H. R., & Weiss, T. (2012). Sensory feedback prosthesis reduces phantom limb pain: Proof of a principle. Neuroscience Letters, 507(2), 97-100. https://doi.org/10.1016/j.neulet.2011.10.068
Dinse, H. R. (2003). Pharmacological modulation of perceptual learning and associated cortical reorganization. Science, 301(5629), 91-94. https://doi.org/10.1126/science.1085423
Dixon, W. J., & Mood, A. M. (1948). A method for obtaining and analyzing sensitivity data. Journal of the American Statistical Association, 43(241), 109-126. https://doi.org/10.1080/01621459.1948.10483254
Drummond, P. D., & Finch, P. M. (2006). Sensory changes in the forehead of patients with complex regional pain syndrome. Pain, 123(1-2), 83-89. https://doi.org/10.1016/j.pain.2006.02.013
Engkvist, O., Wahren, L. K., Wallin, G., Torebjrk, E., & Nystrm, B. (1985). Effects of regional intravenous guanethidine block in posttraumatic cold intolerance in hand amputees. Journal of Hand Surgery (British and European Volume), 10(2), 145-150. https://doi.org/10.1016/0266-7681(85)90003-8
Flor, H. (2002). Phantom-limb pain: Characteristics, causes, and treatment. The Lancet Neurology, 1(3), 182-189. https://doi.org/10.1016/S1474-4422(02)00074-1
Flor, H., Elbert, T., Knecht, S., Wienbruch, C., Pantev, C., Birbaumers, N., Larbig, W., & Taub, E. (1995). Phantom-limb pain as a perceptual correlate of cortical reorganization following arm amputation. Nature, 375(6531), 482-484. https://doi.org/10.1038/375482a0
Flor, H., Elbert, T., Mühlnickel, W., Pantev, C., Wienbruch, C., & Taub, E. (1998). Cortical reorganization and phantom phenomena in congenital and traumatic upper-extremity amputees. Experimental Brain Research, 119(2), 205-212. https://doi.org/10.1007/s002210050334
Flor, H., & Fuchs, X. (2017). Phantom limb pain. In Reference module in neuroscience and biobehavioral psychology. Elsevier. https://www.sciencedirect.com/science/article/pii/B9780128093245031436
Flor, H., Nikolajsen, L., & Jensen, T. S. (2006). Phantom limb pain: A case of maladaptive CNS plasticity? Nature Reviews Neuroscience, 7(11), 873-881. https://doi.org/10.1038/nrn1991
Flor, H., Rudy, T. E., Birbaumer, N., Streit, B., & Schugens, M. M. (1990). Zur Anwendbarkeit des West Haven-Yale Multidimensional Pain Inventory im deutschen Sprachraum [The applicability of the West Haven-Yale multidimensional pain inventory in German-speaking countries. Data on the reliability and validity of the MPI-D.]. Der Schmerz, 4(2), 82-87. https://doi.org/10.1007/BF02527839
Flor, H., & Turk, D. C. (2011). Chronic pain: An integrated biobehavioral approach (1 Pap/Cdr edition). IASP Press.
Fried, K., Govrin-Lippmann, R., Rosenthal, F., Ellisman, M. H., & Devor, M. (1991). Ultrastructure of afferent axon endings in a neuroma. Journal of Neurocytology, 20(8), 682-701. https://doi.org/10.1007/BF01187069
Fuchs, X., Bekrater-Bodmann, R., & Flor, H. (2015). Phantom pain: The role of maladaptive plasticity and emotional and cognitive variables. In G. Pickering & S. Gibson (Eds.), Pain, emotion and cognition (pp. 189-207). Springer International Publishing. https://doi.org/10.1007/978-3-319-12033-1_12
Fuchs, X., Flor, H., & Bekrater-Bodmann, R. (2018). Psychological factors associated with phantom limb pain: A review of recent findings. Pain Research and Management, 2018, 5080123. https://doi.org/10.1155/2018/5080123
Granot, M. (2009). Can we predict persistent postoperative pain by testing preoperative experimental pain? Current Opinion in Anaesthesiology, 22(3), 425-430. https://doi.org/10.1097/ACO.0b013e32832a40e1
Grüsser, S. M., Winter, C., Mühlnickel, W., Denke, C., Karl, A., Villringer, K., & Flor, H. (2001). The relationship of perceptual phenomena and cortical reorganization in upper extremity amputees. Neuroscience, 102(2), 263-272. https://doi.org/10.1016/S0306-4522(00)00491-7
Haber, W. B. (1955). Effects of loss of limb on sensory functions. The Journal of Psychology, 40(1), 115-123. https://doi.org/10.1080/00223980.1955.9712969
Harden, R. N., Gagnon, C. M., Khan, A., Wallach, G., & Zereshki, A. (2010). Hypoesthesia in the distal residual limb of amputees. PM&R, 2(7), 607-611. https://doi.org/10.1016/j.pmrj.2010.03.033
Hunter, J. P., Katz, J., & Davis, K. D. (2005). Dissociation of phantom limb phenomena from stump tactile spatial acuity and sensory thresholds. Brain, 128(2), 308-320. https://doi.org/10.1093/brain/awh350
Katz, D. (1921). Zur Psychologie des Amputierten und seiner Prothese. Barth.
Katz, J. (1992). Psychophysical correlates of phantom limb experience. Journal of Neurology, Neurosurgery & Psychiatry, 55(9), 811-821. https://doi.org/10.1136/jnnp.55.9.811
Kern, U., Busch, V., Rockland, M., Kohl, M., & Birklein, F. (2009). Prävalenz und Risikofaktoren von Phantomschmerzen und Phantomwahrnehmungen in Deutschland [Prevalence and risk factors of phantom limb pain and phantom limb sensations in Germany. A nationwide field survey]. Schmerz (Berlin, Germany), 23(5), 479-488. https://doi.org/10.1007/s00482-009-0786-5
Kerns, R. D., Turk, D. C., & Rudy, T. E. (1985). The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain, 23(4), 345-356. https://doi.org/10.1016/0304-3959(85)90004-1
Kikkert, S., Johansen-Berg, H., Tracey, I., & Makin, T. R. (2018). Reaffirming the link between chronic phantom limb pain and maintained missing hand representation. Cortex, 106, 174-184. https://doi.org/10.1016/j.cortex.2018.05.013
Kleinböhl, D., Hölzl, R., Möltner, A., Rommel, C., Weber, C., & Osswald, P. M. (1999). Psychophysical measures of sensitization to tonic heat discriminate chronic pain patients. Pain, 81(1), 35-43. https://doi.org/10.1016/S0304-3959(98)00266-8
Korin, H., Weiss, S. A., & Fishman, S. (1963). Pain sensitivity of amputation extremities. The Journal of Psychology, 55(2), 345-355. https://doi.org/10.1080/00223980.1963.9916627
Kuznetsova, A., Brockhoff, P. B., & Christensen, R. H. B. (2014). lmerTest: Tests for random and fixed effects for linear mixed effect models (lmer objects of lme4 package). http://CRAN.R-project.org/package=lmerTest
Latremoliere, A., & Woolf, C. J. (2009). Central sensitization: A generator of pain hypersensitivity by central neural plasticity. The Journal of Pain, 10(9), 895-926. https://doi.org/10.1016/j.jpain.2009.06.012
Lautenbacher, S., Rollman, G. B., & McCain, G. A. (1994). Multi-method assessment of experimental and clinical pain in patients with fibromyalgia. Pain, 59(1), 45-53. https://doi.org/10.1016/0304-3959(94)90046-9
Le Bars, D. (2002). The whole body receptive field of dorsal horn multireceptive neurones. Brain Research. Brain Research Reviews, 40(1-3), 29-44. https://doi.org/10.1016/S0165-0173(02)00186-8
Le Bars, D., Dickenson, A. H., & Besson, J.-M. (1979). Diffuse noxious inhibitory controls (DNIC). I. Effects on dorsal horn convergent neurones in the rat. Pain, 6(3), 283-304. https://doi.org/10.1016/0304-3959(79)90049-6
Levitt, H. (1971). Transformed up-down methods in psychoacoustics. The Journal of the Acoustical Society of America, 49(2), Suppl2:467+.
Lewis, G. N., Rice, D. A., & McNair, P. J. (2012). Conditioned pain modulation in populations with chronic pain: A systematic review and meta-analysis. The Journal of Pain, 13(10), 936-944. https://doi.org/10.1016/j.jpain.2012.07.005
Li, S., Melton, D. H., & Li, S. (2015). Tactile, thermal, and electrical thresholds in patients with and without phantom limb pain after traumatic lower limb amputation. Journal of Pain Research, 8, 169-174. https://doi.org/10.2147/JPR.S77412
Lotze, M., Flor, H., Grodd, W., Larbig, W., & Birbaumer, N. (2001). Phantom movements and pain An fMRI study in upper limb amputees. Brain, 124(11), 2268-2277. https://doi.org/10.1093/brain/124.11.2268
Lotze, M., Grodd, W., Birbaumer, N., Erb, M., Huse, E., & Flor, H. (1999). Does use of a myoelectric prosthesis prevent cortical reorganization and phantom limb pain? Nature Neuroscience, 2(6), 501-502. https://doi.org/10.1038/9145
MacIver, K., Lloyd, D. M., Kelly, S., Roberts, N., & Nurmikko, T. (2008). Phantom limb pain, cortical reorganization and the therapeutic effect of mental imagery. Brain, 131(8), 2181-2191. https://doi.org/10.1093/brain/awn124
Magerl, W., Krumova, E. K., Baron, R., Tölle, T., Treede, R.-D., & Maier, C. (2010). Reference data for quantitative sensory testing (QST): Refined stratification for age and a novel method for statistical comparison of group data. Pain, 151(3), 598-605. https://doi.org/10.1016/j.pain.2010.07.026
Maier, C., Baron, R., Tölle, T. R., Binder, A., Birbaumer, N., Birklein, F., Gierthmühlen, J., Flor, H., Geber, C., Huge, V., Krumova, E. K., Landwehrmeyer, G. B., Magerl, W., Maihöfner, C., Richter, H., Rolke, R., Scherens, A., Schwarz, A., Sommer, C., … Treede, D.-R. (2010). Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Somatosensory abnormalities in 1236 patients with different neuropathic pain syndromes. Pain, 150(3), 439-450. https://doi.org/10.1016/j.pain.2010.05.002
Makin, T. R., Cramer, A. O., Scholz, J., Hahamy, A., Slater, D. H., Tracey, I., & Johansen-Berg, H. (2013). Deprivation-related and use-dependent plasticity go hand in hand. Elife, 2, e01273. https://doi.org/10.7554/eLife.01273
Makin, T. R., Scholz, J., Filippini, N., Henderson Slater, D., Tracey, I., & Johansen-Berg, H. (2013). Phantom pain is associated with preserved structure and function in the former hand area. Nature Communications, 4, 1570. https://doi.org/10.1038/ncomms2571
Mancini, F., Bauleo, A., Cole, J., Lui, F., Porro, C. A., Haggard, P., & Iannetti, G. D. (2014). Whole-body mapping of spatial acuity for pain and touch: Mapping spatial acuity for pain. Annals of Neurology, 75(6), 917-924, https://doi.org/10.1002/ana.24179
Mansour, A. R., Baliki, M. N., Huang, L., Torbey, S., Herrmann, K. M., Schnitzer, T. J., & Apkarian, A. V. (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
Moseley, G. L. (2008). I can’t find it! Distorted body image and tactile dysfunction in patients with chronic back pain. Pain, 140(1), 239-243. https://doi.org/10.1016/j.pain.2008.08.001
Moseley, G. L., Gallagher, L., & Gallace, A. (2012). Neglect-like tactile dysfunction in chronic back pain. Neurology, 79(4), 327-332. https://doi.org/10.1212/WNL.0b013e318260cba2
Moseley, G. L., & Vlaeyen, J. W. S. (2015). Beyond nociception: The imprecision hypothesis of chronic pain. Pain, 156(1), 35-38. https://doi.org/10.1016/j.pain.0000000000000014
Muret, D., Daligault, S., Dinse, H. R., Delpuech, C., Mattout, J., Reilly, K. T., & Farnè, A. (2016). Neuromagnetic correlates of adaptive plasticity across the hand-face border in human primary somatosensory cortex. Journal of Neurophysiology, 115(4), 2095-2104. https://doi.org/10.1152/jn.00628.2015
Nikolajsen, L. (2013). Phantom limb. In S. B. McMahon, P. D. Wall, & R. Melzack (Eds.), Wall and Melzack’s textbook of pain (6th ed., pp. 915-925). Elsevier, Saunders.
Nikolajsen, L., Ilkjaer, S., & Jensen, T. S. (2000). Relationship between mechanical sensitivity and postamputation pain: A prospective study. European Journal of Pain, 4(4), 327-334. https://doi.org/10.1053/eujp.2000.0194
Nikolajsen, L., Ilkjaer, S., Krøner, K., Christensen, J. H., & Jensen, T. S. (1997). The influence of preamputation pain on postamputation stump and phantom pain. Pain, 72(3), 393-405. https://doi.org/10.1016/S0304-3959(97)00061-4
Oldfield, R. C. (1971). The assessment and analysis of handedness: The Edinburgh inventory. Neuropsychologia, 9(1), 97-113. https://doi.org/10.1016/0028-3932(71)90067-4
Palmer, S., Bailey, J., Brown, C., Jones, A., & McCabe, C. S. (2019). Sensory function and pain experience in arthritis, complex regional pain syndrome, fibromyalgia syndrome, and pain-free volunteers: A cross-sectional study. The Clinical Journal of Pain, 35(11), 894-900. https://doi.org/10.1097/AJP.0000000000000751
Pinheiro, J. C., & Bates, D. M. (2000). Mixed-effects models in S and S-PLUS. Springer Science & Business Media.
R Core Team (2014). R: A language and environment for statistical computing. R Foundation for Statistical Computing. http://www.R-project.org/
Ramachandran, V. S., & Hirstein, W. (1998). The perception of phantom limbs. The D. O. Hebb lecture. Brain, 121(9), 1603-1630. https://doi.org/10.1093/brain/121.9.1603
Rolke, R., Baron, R., Maier, C., Tölle, T. R., Treede, D. R., Beyer, A., Binder, A., Birbaumer, N., Birklein, F., Bötefür, I. C., Braune, S., Flor, H., Huge, V., Klug, R., Landwehrmeyer, G. B., Magerl, W., Maihöfner, C., Rolko, C., Schaub, C., … Wasserka, B. (2006). Quantitative sensory testing in the German Research Network on Neuropathic Pain (DFNS): Standardized protocol and reference values. Pain, 123(3), 231-243. https://doi.org/10.1016/j.pain.2006.01.041
Sherman, R. A., Arena, J. G., Sherman, C. J., & Ernst, J. L. (1989). The mystery of phantom pain: Growing evidence for psychophysiological mechanisms. Biofeedback and Self-Regulation, 14(4), 267-280. https://doi.org/10.1007/BF00999118
Teuber, H.-L., Krieger, H., & Bender, M. (1949). Reorganization of sensory function in amputation stumps: Two-point discrimination. Federal Proceedings, 8:156.
van den Heuvel, M. P., & Hulshoff Pol, H. E. (2009). Specific somatotopic organization of functional connections of the primary motor network during resting state. Human Brain Mapping, 4(31), 631-644. https://doi.org/10.1002/hbm.20893
Vase, L., Nikolajsen, L., Christensen, B., Egsgaard, L. L., Arendt-Nielsen, L., Svensson, P., & Staehelin Jensen, T. (2011). Cognitive-emotional sensitization contributes to wind-up-like pain in phantom limb pain patients. Pain, 152(1), 157-162. https://doi.org/10.1016/j.pain.2010.10.013
Vaso, A., Adahan, H.-M., Gjika, A., Zahaj, S., Zhurda, T., Vyshka, G., & Devor, M. (2014). Peripheral nervous system origin of phantom limb pain. Pain, 155(7), 1384-1391. https://doi.org/10.1016/j.pain.2014.04.018
Vatine, J.-J., Tsenter, J., & Nirel, R. (1998). Experimental pressure pain in patients with complex regional pain syndrome, type I (reflex sympathetic dystrophy). American Journal of Physical Medicine & Rehabilitation, 77(5), 382-387.
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
Wahren, L. K. (1990). Changes in thermal and mechanical pain thresholds in hand amputees. A clinical and physiological long-term follow-up. Pain, 42(3), 269-277. https://doi.org/10.1016/0304-3959(90)91139-A
Weinstein, S. (1968). Intensive and extensive aspects of tactile sensitivity as a function of body part, sex, and laterality. In D. R. Kenshalo (Ed.), The skin senses: Proceedings of the first International Symposium on the Skin Senses, held at the Florida State University in Tallahassee, Florida (pp. 195-218). Charles C. Thomas Publishing.
Wickham, H. (2009). ggplot2: Elegant graphics for data analysis. Springer Science & Business Media.
Wiffen, P., Meynadier, J., Dubois, M., Thurel, C., DeSmet, J., & Harden, R. N. (2006). Chapter 4: Diagnostic and treatment issues in postamputation pain after landmine injury. Pain Medicine, 7(Suppl 2), S209-S212. https://doi.org/10.1111/j.1526-4637.2006.00234_6.x
Wilson, J. J., Wilson, B. C., & Swinyard, C. A. (1962). Two-point discrimination in congenital amputees. Journal of Comparative and Physiological Psychology, 55(4), 482-485. https://doi.org/10.1037/h0042122
Woolf, C. J. (2014). What to call the amplification of nociceptive signals in the central nervous system that contribute to widespread pain? Pain, 155(10), 1911-1912. https://doi.org/10.1016/j.pain.2014.07.021
Woolf, C. J., & Salter, M. W. (2000). Neuronal Plasticity: Increasing the Gain in Pain. Science, 288(5472), 1765-1768. https://doi.org/10.1126/science.288.5472.1765
Yi, M., & Zhang, H. (2011). Nociceptive memory in the brain: Cortical mechanisms of chronic pain. The Journal of Neuroscience, 31(38), 13343-13345. https://doi.org/10.1523/JNEUROSCI.3279-11.2011