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The role of pain modulation pathway and related brain regions in pain

  • Dandan Yao , Yeru Chen and Gang Chen EMAIL logo
Published/Copyright: June 8, 2023
Become an author with De Gruyter Brill

Abstract

Pain is a multifaceted process that encompasses unpleasant sensory and emotional experiences. The essence of the pain process is aversion, or perceived negative emotion. Central sensitization plays a significant role in initiating and perpetuating of chronic pain. Melzack proposed the concept of the “pain matrix”, in which brain regions associated with pain form an interconnected network, rather than being controlled by a singular brain region. This review aims to investigate distinct brain regions involved in pain and their interconnections. In addition, it also sheds light on the reciprocal connectivity between the ascending and descending pathways that participate in pain modulation. We review the involvement of various brain areas during pain and focus on understanding the connections among them, which can contribute to a better understanding of pain mechanisms and provide opportunities for further research on therapies for improved pain management.


Corresponding author: Gang Chen, Department of Anesthesiology, School of Medicine, Shaoxing University, Shaoxing, Zhejiang, China; and Department of Anesthesiology, Sir Run Run Shaw Hospital, School of Medicine, Zhejiang University, Hangzhou, Zhejiang 310058, China, E-mail:

Funding source: Zhejiang Provincial Department of Medicine and Health Science and Technology

Award Identifier / Grant number: No. YH42021010

Award Identifier / Grant number: No.82001424

Award Identifier / Grant number: No.82171176

  1. Author contributions: Gang Chen had the idea for the article; Dandan Yao and Yeru Chen drafted the manuscript. All authors read and approved the final manuscript.

  2. Research funding: This research was supported by the National Natural Science Foundation of China (No.82171176 and No.82001424), and the Zhejiang Provincial Department of Medicine and Health Science and Technology (No. YH42021010).

  3. Conflict of interests: The authors declare no competing interests.

References

Ahrens, S., Wu, M.V., Furlan, A., Hwang, G.R., Paik, R., Li, H., Penzo, M.A., Tollkuhn, J., and Li, B. (2018). A central extended amygdala circuit that modulates anxiety. J. Neurosci. 38: 5567–5583, https://doi.org/10.1523/jneurosci.0705-18.2018.Search in Google Scholar PubMed PubMed Central

Allen, H.N., Bobnar, H.J., and Kolber, B.J. (2021). Left and right hemispheric lateralization of the amygdala in pain. Prog. Neurobiol. 196: 101891, https://doi.org/10.1016/j.pneurobio.2020.101891.Search in Google Scholar PubMed PubMed Central

Allsop, S.A., Wichmann, R., Mills, F., Burgos-Robles, A., Chang, C.J., Felix-Ortiz, A.C., Vienne, A., Beyeler, A., Izadmehr, E.M., Glober, G., et al.. (2018). Corticoamygdala transfer of socially derived information gates observational learning. Cell 173: 1329–1342, https://doi.org/10.1016/j.cell.2018.04.004.Search in Google Scholar PubMed PubMed Central

Alshelh, Z., Di Pietro, F., Youssef, A.M., Reeves, J.M., Macey, P.M., Vickers, E.R., Peck, C.C., Murray, G.M., and Henderson, L.A. (2016). Chronic neuropathic pain: it’s about the rhythm. J. Neurosci. 36: 1008–1018, https://doi.org/10.1523/jneurosci.2768-15.2016.Search in Google Scholar

Apkarian, A.V., Bushnell, M.C., Treede, R.D., and Zubieta, J.K. (2005). Human brain mechanisms of pain perception and regulation in health and disease. Eur. J. Pain 9: 463–484, https://doi.org/10.1016/j.ejpain.2004.11.001.Search in Google Scholar PubMed

Apkarian, V.A., Hashmi, J.A., and Baliki, M.N. (2011). Pain and the brain: specificity and plasticity of the brain in clinical chronic pain. Pain 152: S49–S64, https://doi.org/10.1016/j.pain.2010.11.010.Search in Google Scholar PubMed PubMed Central

Autry, A.E. and Monteggia, L.M. (2012). Brain-derived neurotrophic factor and neuropsychiatric disorders. Pharmacol. Rev. 64: 238–258, https://doi.org/10.1124/pr.111.005108.Search in Google Scholar PubMed PubMed Central

Bagley, E.E. and Ingram, S.L. (2020). Endogenous opioid peptides in the descending pain modulatory circuit. Neuropharmacology 173: 108131, https://doi.org/10.1016/j.neuropharm.2020.108131.Search in Google Scholar PubMed PubMed Central

Barthas, F., Sellmeijer, J., Hugel, S., Waltisperger, E., Barrot, M., and Yalcin, I. (2015). The anterior cingulate cortex is a critical hub for pain-induced depression. Biol. Psychiatry 77: 236–245, https://doi.org/10.1016/j.biopsych.2014.08.004.Search in Google Scholar PubMed

Benarroch, E.E. (2019). Insular cortex: functional complexity and clinical correlations. Neurology 93: 932–938, https://doi.org/10.1212/wnl.0000000000008525.Search in Google Scholar

Benison, A.M., Chumachenko, S., Harrison, J.A., Maier, S.F., Falci, S.P., Watkins, L.R., and Barth, D.S. (2011). Caudal granular insular cortex is sufficient and necessary for the long-term maintenance of allodynic behavior in the rat attributable to mononeuropathy. J. Neurosci. 31: 6317–6328, https://doi.org/10.1523/jneurosci.0076-11.2011.Search in Google Scholar PubMed PubMed Central

Beukema, P., Cecil, K.L., Peterson, E., Mann, V.R., Matsushita, M., Takashima, Y., Navlakha, S., and Barth, A.L. (2018). TrpM8-mediated somatosensation in mouse neocortex. J. Comp. Neurol. 526: 1444–1456, https://doi.org/10.1002/cne.24418.Search in Google Scholar PubMed PubMed Central

Bloodgood, D.W., Sugam, J.A., Holmes, A., and Kash, T.L. (2018). Fear extinction requires infralimbic cortex projections to the basolateral amygdala. Transl. Psychiatry 8: 60, https://doi.org/10.1038/s41398-018-0106-x.Search in Google Scholar PubMed PubMed Central

Bokiniec, P., Zampieri, N., Lewin, G.R., and Poulet, J.F. (2018). The neural circuits of thermal perception. Curr. Opin. Neurobiol. 52: 98–106, https://doi.org/10.1016/j.conb.2018.04.006.Search in Google Scholar PubMed PubMed Central

Bourne, S., Machado, A.G., and Nagel, S.J. (2014). Basic anatomy and physiology of pain pathways. Neurosurg. Clin. N. Am. 25: 629–638, https://doi.org/10.1016/j.nec.2014.06.001.Search in Google Scholar PubMed

Bushnell, M.C., Ceko, M., and Low, L.A. (2013). Cognitive and emotional control of pain and its disruption in chronic pain. Nat. Rev. Neurosci. 14: 502–511, https://doi.org/10.1038/nrn3516.Search in Google Scholar PubMed PubMed Central

Bushnell, M.C., Duncan, G.H., Hofbauer, R.K., Ha, B., Chen, J.I., and Carrier, B. (1999). Pain perception: is there a role for primary somatosensory cortex? Proc. Natl. Acad. Sci. U. S. A. 96: 7705–7709, https://doi.org/10.1073/pnas.96.14.7705.Search in Google Scholar PubMed PubMed Central

Butler, R.K., Nilsson-Todd, L., Cleren, C., Léna, I., Garcia, R., and Finn, D.P. (2011). Molecular and electrophysiological changes in the prefrontal cortex-amygdala-dorsal periaqueductal grey pathway during persistent pain state and fear-conditioned analgesia. Physiol. Behav. 104: 1075–1081, https://doi.org/10.1016/j.physbeh.2011.05.028.Search in Google Scholar PubMed

Cai, H., Haubensak, W., Anthony, T.E., and Anderson, D.J. (2014). Central amygdala PKC-δ(+) neurons mediate the influence of multiple anorexigenic signals. Nat. Neurosci. 17: 1240–1248, https://doi.org/10.1038/nn.3767.Search in Google Scholar PubMed PubMed Central

Cai, Y.Q., Wang, W., Paulucci-Holthauzen, A., and Pan, Z.Z. (2018). Brain circuits mediating opposing effects on emotion and pain. J. Neurosci. 38: 6340–6349, https://doi.org/10.1523/jneurosci.2780-17.2018.Search in Google Scholar PubMed PubMed Central

Cardoso-Cruz, H., Paiva, P., Monteiro, C., and Galhardo, V. (2019). Selective optogenetic inhibition of medial prefrontal glutamatergic neurons reverses working memory deficits induced by neuropathic pain. Pain 160: 805–823, https://doi.org/10.1097/j.pain.0000000000001457.Search in Google Scholar PubMed

Cardoso-Cruz, H., Sousa, M., Vieira, J.B., Lima, D., and Galhardo, V. (2013). Prefrontal cortex and mediodorsal thalamus reduced connectivity is associated with spatial working memory impairment in rats with inflammatory pain. Pain 154: 2397–2406, https://doi.org/10.1016/j.pain.2013.07.020.Search in Google Scholar PubMed

Carlén, M. (2017). What constitutes the prefrontal cortex? Science 358: 478–482, https://doi.org/10.1126/science.aan8868.Search in Google Scholar PubMed

Cavalcanti, M.R.M., Passos, F.R.S., Monteiro, B.S., Gandhi, S.R., Heimfarth, L., Lima, B.S., Nascimento, Y.M., Duarte, M.C., Araujo, A.A.S., Menezes, I.R.A., et al.. (2021). HPLC-DAD-UV analysis, anti-inflammatory and anti-neuropathic effects of methanolic extract of Sideritis bilgeriana (lamiaceae) by NF-κB, TNF-α, IL-1β and IL-6 involvement. J. Ethnopharmacol. 265: 113338, https://doi.org/10.1016/j.jep.2020.113338.Search in Google Scholar PubMed

Chao, T.H., Chen, J.H., and Yen, C.T. (2018). Plasticity changes in forebrain activity and functional connectivity during neuropathic pain development in rats with sciatic spared nerve injury. Mol. Brain 11: 55, https://doi.org/10.1186/s13041-018-0398-z.Search in Google Scholar PubMed PubMed Central

Chen, J.I., Ha, B., Bushnell, M.C., Pike, B., and Duncan, G.H. (2002). Differentiating noxious- and innocuous-related activation of human somatosensory cortices using temporal analysis of fMRI. J. Neurophysiol. 88: 464–474, https://doi.org/10.1152/jn.2002.88.1.464.Search in Google Scholar PubMed

Chen, Q. and Heinricher, M.M. (2022). Shifting the balance: how top-down and bottom-up input modulate pain via the rostral ventromedial medulla. Front. Pain Res. (Lausanne) 3: 932476, https://doi.org/10.3389/fpain.2022.932476.Search in Google Scholar PubMed PubMed Central

Chen, T., Taniguchi, W., Chen, Q.Y., Tozaki-Saitoh, H., Song, Q., Liu, R.H., Koga, K., Matsuda, T., Kaito-Sugimura, Y., Wang, J., et al.. (2018). Top-down descending facilitation of spinal sensory excitatory transmission from the anterior cingulate cortex. Nat. Commun. 9: 1886, https://doi.org/10.1038/s41467-018-04309-2.Search in Google Scholar PubMed PubMed Central

Chen, Y.H., Wu, J.L., Hu, N.Y., Zhuang, J.P., Li, W.P., Zhang, S.R., Li, X.W., Yang, J.M., and Gao, T.M. (2021). Distinct projections from the infralimbic cortex exert opposing effects in modulating anxiety and fear. J. Clin. Invest. 131: 2–4, https://doi.org/10.1172/jci145692.Search in Google Scholar PubMed PubMed Central

Chiang, M.C., Bowen, A., Schier, L.A., Tupone, D., Uddin, O., and Heinricher, M.M. (2019). Parabrachial complex: a hub for pain and aversion. J. Neurosci. 39: 8225–8230, https://doi.org/10.1523/jneurosci.1162-19.2019.Search in Google Scholar PubMed PubMed Central

Chiang, M.C., Nguyen, E.K., Canto-Bustos, M., Papale, A.E., Oswald, A.M., and Ross, S.E. (2020). Divergent neural pathways emanating from the lateral parabrachial nucleus mediate distinct components of the pain response. Neuron 106: 927–939, https://doi.org/10.1016/j.neuron.2020.03.014.Search in Google Scholar PubMed

Ching, Y.Y., Wang, C., Tay, T., Loke, Y.M., Tang, P.H., Sng, B.L., and Zhou, J. (2018). Altered sensory insular connectivity in chronic postsurgical pain patients. Front. Hum. Neurosci. 12: 483, https://doi.org/10.3389/fnhum.2018.00483.Search in Google Scholar PubMed PubMed Central

Coghill, R.C., Sang, C.N., Maisog, J.M., and Iadarola, M.J. (1999). Pain intensity processing within the human brain: a bilateral, distributed mechanism. J. Neurophysiol. 82: 1934–1943, https://doi.org/10.1152/jn.1999.82.4.1934.Search in Google Scholar PubMed

Cohen, S.P. and Mao, J. (2014). Neuropathic pain: mechanisms and their clinical implications. Brit. Med. J. 348: f7656, https://doi.org/10.1136/bmj.f7656.Search in Google Scholar PubMed

Cohen, S.P., Vase, L., and Hooten, W.M. (2021). Chronic pain: an update on burden, best practices, and new advances. Lancet 397: 2082–2097, https://doi.org/10.1016/s0140-6736(21)00393-7.Search in Google Scholar

Cottam, W.J., Iwabuchi, S.J., Drabek, M.M., Reckziegel, D., and Auer, D.P. (2018). Altered connectivity of the right anterior insula drives the pain connectome changes in chronic knee osteoarthritis. Pain 159: 929–938, https://doi.org/10.1097/j.pain.0000000000001209.Search in Google Scholar PubMed PubMed Central

Craig, A.D. (2002). How do you feel? Interoception: the sense of the physiological condition of the body. Nat. Rev. Neurosci. 3: 655–666, https://doi.org/10.1038/nrn894.Search in Google Scholar PubMed

Craig, A.D. (2003). Interoception: the sense of the physiological condition of the body. Curr. Opin. Neurobiol. 13: 500–505, https://doi.org/10.1016/s0959-4388(03)00090-4.Search in Google Scholar PubMed

Craig, A.D. (2014). Topographically organized projection to posterior insular cortex from the posterior portion of the ventral medial nucleus in the long-tailed macaque monkey. J. Comp. Neurol. 522: 36–63, https://doi.org/10.1002/cne.23425.Search in Google Scholar PubMed PubMed Central

Dale, J., Zhou, H., Zhang, Q., Martinez, E., Hu, S., Liu, K., Urien, L., Chen, Z., and Wang, J. (2018). Scaling up cortical control inhibits pain. Cell Rep. 23: 1301–1313, https://doi.org/10.1016/j.celrep.2018.03.139.Search in Google Scholar PubMed PubMed Central

David-Pereira, A., Puga, S., Gonçalves, S., Amorim, D., Silva, C., Pertovaara, A., Almeida, A., and Pinto-Ribeiro, F. (2016). Metabotropic glutamate 5 receptor in the infralimbic cortex contributes to descending pain facilitation in healthy and arthritic animals. Neuroscience 312: 108–119, https://doi.org/10.1016/j.neuroscience.2015.10.060.Search in Google Scholar PubMed

David-Pereira, A., Sagalajev, B., Wei, H., Almeida, A., Pertovaara, A., and Pinto-Ribeiro, F. (2017). The medullary dorsal reticular nucleus as a relay for descending pronociception induced by the mGluR5 in the rat infralimbic cortex. Neuroscience 349: 341–354, https://doi.org/10.1016/j.neuroscience.2017.02.046.Search in Google Scholar PubMed

De Ridder, D., Adhia, D., and Vanneste, S. (2021). The anatomy of pain and suffering in the brain and its clinical implications. Neurosci. Biobehav. Rev. 130: 125–146, https://doi.org/10.1016/j.neubiorev.2021.08.013.Search in Google Scholar PubMed

De Ridder, D. and Vanneste, S. (2017). Occipital nerve field transcranial direct current stimulation normalizes imbalance between pain detecting and pain inhibitory pathways in fibromyalgia. Neurotherapeutics 14: 484–501, https://doi.org/10.1007/s13311-016-0493-8.Search in Google Scholar PubMed PubMed Central

Devoize, L., Alvarez, P., Monconduit, L., and Dallel, R. (2011). Representation of dynamic mechanical allodynia in the ventral medial prefrontal cortex of trigeminal neuropathic rats. Eur. J. Pain 15: 676–682, https://doi.org/10.1016/j.ejpain.2010.11.017.Search in Google Scholar PubMed

Donaldson, L.F. and Lumb, B.M. (2017). Top-down control of pain. J. Physiol. 595: 4139–4140, https://doi.org/10.1113/jp273361.Search in Google Scholar PubMed PubMed Central

Drake, R.A., Steel, K.A., Apps, R., Lumb, B.M., and Pickering, A.E. (2021). Loss of cortical control over the descending pain modulatory system determines the development of the neuropathic pain state in rats. Elife 10: 4–7, https://doi.org/10.7554/elife.65156.Search in Google Scholar

Dum, R.P., Levinthal, D.J., and Strick, P.L. (2009). The spinothalamic system targets motor and sensory areas in the cerebral cortex of monkeys. J. Neurosci. 29: 14223–14235, https://doi.org/10.1523/jneurosci.3398-09.2009.Search in Google Scholar PubMed PubMed Central

Eippert, F., Bingel, U., Schoell, E.D., Yacubian, J., Klinger, R., Lorenz, J., and Büchel, C. (2009). Activation of the opioidergic descending pain control system underlies placebo analgesia. Neuron 63: 533–543, https://doi.org/10.1016/j.neuron.2009.07.014.Search in Google Scholar PubMed

Eto, K., Ishibashi, H., Yoshimura, T., Watanabe, M., Miyamoto, A., Ikenaka, K., Moorhouse, A.J., and Nabekura, J. (2012). Enhanced GABAergic activity in the mouse primary somatosensory cortex is insufficient to alleviate chronic pain behavior with reduced expression of neuronal potassium-chloride cotransporter. J. Neurosci. 32: 16552–16559, https://doi.org/10.1523/jneurosci.2104-12.2012.Search in Google Scholar

Fields, H. (2004). State-dependent opioid control of pain. Nat. Rev. Neurosci. 5: 565–575, https://doi.org/10.1038/nrn1431.Search in Google Scholar PubMed

Fields, H.L. (2000). Pain modulation: expectation, opioid analgesia and virtual pain. Prog. Brain Res. 122: 245–253, https://doi.org/10.1016/s0079-6123(08)62143-3.Search in Google Scholar PubMed

François, A., Low, S.A., Sypek, E.I., Christensen, A.J., Sotoudeh, C., Beier, K.T., Ramakrishnan, C., Ritola, K.D., Sharif-Naeini, R., Deisseroth, K., et al.. (2017). A Brainstem-spinal cord inhibitory circuit for mechanical pain modulation by GABA and enkephalins. Neuron 93: 822–839, https://doi.org/10.1016/j.neuron.2017.01.008.Search in Google Scholar PubMed PubMed Central

Friebel, U., Eickhoff, S.B., and Lotze, M. (2011). Coordinate-based meta-analysis of experimentally induced and chronic persistent neuropathic pain. Neuroimage 58: 1070–1080, https://doi.org/10.1016/j.neuroimage.2011.07.022.Search in Google Scholar PubMed PubMed Central

Frøkjær, J.B., Olesen, S.S., Graversen, C., Andresen, T., Lelic, D., and Drewes, A.M. (2018). Neuroimaging of the human visceral pain system-a methodological review. Scand. J. Pain 2: 95–104, https://doi.org/10.1016/j.sjpain.2011.02.006.Search in Google Scholar PubMed

Frot, M., Mauguière, F., Magnin, M., and Garcia-Larrea, L. (2008). Parallel processing of nociceptive A-delta inputs in SII and midcingulate cortex in humans. J. Neurosci. 28: 944–952, https://doi.org/10.1523/jneurosci.2934-07.2008.Search in Google Scholar PubMed PubMed Central

Fuchs, P.N., Peng, Y.B., Boyette-Davis, J.A., and Uhelski, M.L. (2014). The anterior cingulate cortex and pain processing. Front. Integr. Neurosci. 8: 35, https://doi.org/10.3389/fnint.2014.00035.Search in Google Scholar PubMed PubMed Central

Galhardoni, R., Aparecida da Silva, V., García-Larrea, L., Dale, C., Baptista, A.F., Barbosa, L.M., Menezes, L.M.B., de Siqueira, Srdt, Valério, F., Rosi, J.Jr., et al.. (2019). Insular and anterior cingulate cortex deep stimulation for central neuropathic pain: disassembling the percept of pain. Neurology 92: e2165–e75, https://doi.org/10.1212/wnl.0000000000007396.Search in Google Scholar

Gao, S.H., Wen, H.Z., Shen, L.L., Zhao, Y.D., and Ruan, H.Z. (2016). Activation of mGluR1 contributes to neuronal hyperexcitability in the rat anterior cingulate cortex via inhibition of HCN channels. Neuropharmacology 105: 361–377, https://doi.org/10.1016/j.neuropharm.2016.01.036.Search in Google Scholar PubMed

Garro-Martínez, E., Fullana, M.N., Florensa-Zanuy, E., Senserrich, J., Paz, V., Ruiz-Bronchal, E., Adell, A., Castro, E., Díaz, Á., Pazos, Á, et al. (2021). mTOR knockdown in the infralimbic cortex evokes a depressive-like state in mouse. Int. J. Mol. Sci. 22: 1–5, https://doi.org/10.3390/ijms22168671.Search in Google Scholar PubMed PubMed Central

Ge, J., Cai, Y., and Pan, Z.Z. (2022). Synaptic plasticity in two cell types of central amygdala for regulation of emotion and pain. Front. Cell Neurosci. 16: 997360, https://doi.org/10.3389/fncel.2022.997360.Search in Google Scholar PubMed PubMed Central

Giesecke, T., Gracely, R.H., Grant, M.A., Nachemson, A., Petzke, F., Williams, D.A., and Clauw, D.J. (2004). Evidence of augmented central pain processing in idiopathic chronic low back pain. Arthritis Rheum 50: 613–623, https://doi.org/10.1002/art.20063.Search in Google Scholar PubMed

Goadsby, P.J., Holland, P.R., Martins-Oliveira, M., Hoffmann, J., Schankin, C., and Akerman, S. (2017). Pathophysiology of migraine: a disorder of sensory processing. Physiol. Rev. 97: 553–622, https://doi.org/10.1152/physrev.00034.2015.Search in Google Scholar PubMed PubMed Central

Griessner, J., Pasieka, M., Böhm, V., Grössl, F., Kaczanowska, J., Pliota, P., Kargl, D., Werner, B., Kaouane, N., Strobelt, S., et al.. (2021). Central amygdala circuit dynamics underlying the benzodiazepine anxiolytic effect. Mol. Psychiatry 26: 534–544, https://doi.org/10.1038/s41380-018-0310-3.Search in Google Scholar PubMed PubMed Central

Gustin, S.M., Wrigley, P.J., Youssef, A.M., McIndoe, L., Wilcox, S.L., Rae, C.D., Edden, R.A.E., Siddall, P.J., and Henderson, L.A. (2014). Thalamic activity and biochemical changes in individuals with neuropathic pain after spinal cord injury. Pain 155: 1027–1036, https://doi.org/10.1016/j.pain.2014.02.008.Search in Google Scholar PubMed PubMed Central

Han, J., Cha, M., Kwon, M., Hong, S.K., Bai, S.J., and Lee, B.H. (2016). In vivo voltage-sensitive dye imaging of the insular cortex in nerve-injured rats. Neurosci. Lett. 634: 146–152, https://doi.org/10.1016/j.neulet.2016.10.015.Search in Google Scholar PubMed

Hao, S., Yang, H., Wang, X., He, Y., Xu, H., Wu, X., Pan, L., Liu, Y., Lou, H., Xu, H., et al.. (2019). The lateral hypothalamic and BNST GABAergic projections to the anterior ventrolateral periaqueductal gray regulate feeding. Cell Rep. 28: 616–624, https://doi.org/10.1016/j.celrep.2019.06.051.Search in Google Scholar PubMed

Hashmi, J.A., Baliki, M.N., Huang, L., Baria, A.T., Torbey, S., Hermann, K.M., Schnitzer, T.J., and Apkarian, A.V. (2013). Shape shifting pain: chronification of back pain shifts brain representation from nociceptive to emotional circuits. Brain 136: 2751–2768, https://doi.org/10.1093/brain/awt211.Search in Google Scholar PubMed PubMed Central

Heinricher, M.M., Morgan, M.M., Tortorici, V., and Fields, H.L. (1994). Disinhibition of off-cells and antinociception produced by an opioid action within the rostral ventromedial medulla. Neuroscience 63: 279–288, https://doi.org/10.1016/0306-4522(94)90022-1.Search in Google Scholar PubMed

Heinricher, M.M., Tavares, I., Leith, J.L., and Lumb, B.M. (2009). Descending control of nociception: specificity, recruitment and plasticity. Brain Res. Rev. 60: 214–225, https://doi.org/10.1016/j.brainresrev.2008.12.009.Search in Google Scholar PubMed PubMed Central

Hogri, R., Teuchmann, H.L., Heinke, B., Holzinger, R., Trofimova, L., and Sandkühler, J. (2022). GABAergic CaMKIIα+ amygdala output attenuates pain and modulates emotional-motivational behavior via parabrachial inhibition. J. Neurosci. 42: 5373–5388, https://doi.org/10.1523/jneurosci.2067-21.2022.Search in Google Scholar PubMed PubMed Central

Hon, O.J., DiBerto, J.F., Mazzone, C.M., Sugam, J., Bloodgood, D.W., Hardaway, J.A., Husain, M., Kendra, A., McCall, N.M., Lopez, A.J., et al.. (2022). Serotonin modulates an inhibitory input to the central amygdala from the ventral periaqueductal gray. Neuropsychopharmacology 47: 2194–2204, https://doi.org/10.1038/s41386-022-01392-4.Search in Google Scholar PubMed PubMed Central

Hsieh, P.C., Tseng, M.T., Chao, C.C., Lin, Y.H., Tseng, W.I., Liu, K.H., Chiang, M.C., and Hsieh, S.T. (2015). Imaging signatures of altered brain responses in small-fiber neuropathy: reduced functional connectivity of the limbic system after peripheral nerve degeneration. Pain 156: 904–916, https://doi.org/10.1097/j.pain.0000000000000128.Search in Google Scholar PubMed

Huang, D., Grady, F.S., Peltekian, L., Laing, J.J., and Geerling, J.C. (2021). Efferent projections of CGRP/Calca-expressing parabrachial neurons in mice. J. Comp. Neurol. 529: 2911–2957, https://doi.org/10.1002/cne.25136.Search in Google Scholar PubMed PubMed Central

Huang, J., Gadotti, V.M., Chen, L., Souza, I.A., Huang, S., Wang, D., Ramakrishnan, C., Deisseroth, K., Zhang, Z., and Zamponi, G.W. (2019). A neuronal circuit for activating descending modulation of neuropathic pain. Nat. Neurosci. 22: 1659–1668, https://doi.org/10.1038/s41593-019-0481-5.Search in Google Scholar PubMed

Hwang, K., Bertolero, M.A., Liu, W.B., and D’Esposito, M. (2017). The Human thalamus is an integrative hub for functional brain networks. J. Neurosci. 37: 5594–5607, https://doi.org/10.1523/jneurosci.0067-17.2017.Search in Google Scholar

Inami, C., Tanihira, H., Kikuta, S., Ogasawara, O., Sobue, K., Kume, K., Osanai, M., and Ohsawa, M. (2019). Visualization of brain activity in a neuropathic pain model using quantitative activity-dependent manganese magnetic resonance imaging. Front. Neural. Circuits 13: 74, https://doi.org/10.3389/fncir.2019.00074.Search in Google Scholar PubMed PubMed Central

Jarrin, S., Pandit, A., Roche, M., and Finn, D.P. (2020). Differential role of anterior cingulate cortical glutamatergic neurons in pain-related aversion learning and nociceptive behaviors in male and female rats. Front. Behav. Neurosci. 14: 139, https://doi.org/10.3389/fnbeh.2020.00139.Search in Google Scholar PubMed PubMed Central

Jhang, J., Lee, H., Kang, M.S., Lee, H.S., Park, H., and Han, J.H. (2018). Anterior cingulate cortex and its input to the basolateral amygdala control innate fear response. Nat. Commun. 9: 2744, https://doi.org/10.1038/s41467-018-05090-y.Search in Google Scholar PubMed PubMed Central

Ji, G., Sun, H., Fu, Y., Li, Z., Pais-Vieira, M., Galhardo, V., and Neugebauer, V. (2010). Cognitive impairment in pain through amygdala-driven prefrontal cortical deactivation. J. Neurosci. 30: 5451–5464, https://doi.org/10.1523/jneurosci.0225-10.2010.Search in Google Scholar

Jiang, Z.C., Pan, Q., Zheng, C., Deng, X.F., Wang, J.Y., and Luo, F. (2014). Inactivation of the prelimbic rather than infralimbic cortex impairs acquisition and expression of formalin-induced conditioned place avoidance. Neurosci. Lett. 569: 89–93, https://doi.org/10.1016/j.neulet.2014.03.074.Search in Google Scholar PubMed PubMed Central

Johansen, J.P. and Fields, H.L. (2004). Glutamatergic activation of anterior cingulate cortex produces an aversive teaching signal. Nat. Neurosci. 7: 398–403, https://doi.org/10.1038/nn1207.Search in Google Scholar PubMed

Jones, A.F. and Sheets, P.L. (2020). Sex-specific disruption of distinct mPFC inhibitory neurons in spared-nerve injury model of neuropathic pain. Cell Rep. 31: 107729, https://doi.org/10.1016/j.celrep.2020.107729.Search in Google Scholar PubMed PubMed Central

Joo, S.Y., Park, C.H., Cho, Y.S., Seo, C.H., and Ohn, S.H. (2021). Plastic changes in pain and motor network induced by chronic burn pain. J. Clin. Med. 10: 6–8, https://doi.org/10.3390/jcm10122592.Search in Google Scholar PubMed PubMed Central

Juarez-Salinas, D.L., Braz, J.M., Etlin, A., Gee, S., Sohal, V., and Basbaum, A.I. (2019). GABAergic cell transplants in the anterior cingulate cortex reduce neuropathic pain aversiveness. Brain 142: 2655–2669, https://doi.org/10.1093/brain/awz203.Search in Google Scholar PubMed PubMed Central

Kato, F., Sugimura, Y.K., and Takahashi, Y. (2018). Pain-associated neural plasticity in the parabrachial to central amygdala circuit : pain changes the brain, and the brain changes the pain. Adv. Exp. Med. Biol. 1099: 157–166, https://doi.org/10.1007/978-981-13-1756-9_14.Search in Google Scholar PubMed

Kelly, C.J., Huang, M., Meltzer, H., and Martina, M. (2016). Reduced glutamatergic currents and dendritic branching of layer 5 pyramidal cells contribute to medial prefrontal cortex deactivation in a rat model of neuropathic pain. Front. Cell Neurosci. 10: 133, https://doi.org/10.3389/fncel.2016.00133.Search in Google Scholar PubMed PubMed Central

Kelly, C.J. and Martina, M. (2018). Circuit-selective properties of glutamatergic inputs to the rat prelimbic cortex and their alterations in neuropathic pain. Brain Struct. Funct. 223: 2627–2639, https://doi.org/10.1007/s00429-018-1648-7.Search in Google Scholar PubMed PubMed Central

Kikkert, S., Mezue, M., O’Shea, J., Henderson Slater, D., Johansen-Berg, H., Tracey, I., and Makin, T.R. (2019). Neural basis of induced phantom limb pain relief. Ann. Neurol. 85: 59–73, https://doi.org/10.1002/ana.25371.Search in Google Scholar PubMed PubMed Central

Kim, J., Pignatelli, M., Xu, S., Itohara, S., and Tonegawa, S. (2016). Antagonistic negative and positive neurons of the basolateral amygdala. Nat. Neurosci. 19: 1636–1646, https://doi.org/10.1038/nn.4414.Search in Google Scholar PubMed PubMed Central

Kim, J., Zhang, X., Muralidhar, S., LeBlanc, S.A., and Tonegawa, S. (2017). Basolateral to central amygdala neural circuits for appetitive behaviors. Neuron 93: 1464–1479, https://doi.org/10.1016/j.neuron.2017.02.034.Search in Google Scholar

Kim, S.K., Hayashi, H., Ishikawa, T., Shibata, K., Shigetomi, E., Shinozaki, Y., Inada, H., Roh, S.E., Kim, S.J., Lee, G., et al.. (2016). Cortical astrocytes rewire somatosensory cortical circuits for peripheral neuropathic pain. J. Clin. Invest. 126: 1983–1997, https://doi.org/10.1172/jci82859.Search in Google Scholar

Kim, W., Kim, S.K., and Nabekura, J. (2017). Functional and structural plasticity in the primary somatosensory cortex associated with chronic pain. J. Neurochem. 141: 499–506, https://doi.org/10.1111/jnc.14012.Search in Google Scholar

Kiritoshi, T., Ji, G., and Neugebauer, V. (2016). Rescue of impaired mGluR5-driven endocannabinoid signaling restores prefrontal cortical output to inhibit pain in arthritic rats. J. Neurosci. 36: 837–850, https://doi.org/10.1523/jneurosci.4047-15.2016.Search in Google Scholar

Koga, K., Descalzi, G., Chen, T., Ko, H.G., Lu, J., Li, S., Son, J., Kim, T., Kwak, C., Huganir, R.L., et al.. (2015). Coexistence of two forms of LTP in ACC provides a synaptic mechanism for the interactions between anxiety and chronic pain. Neuron 85: 377–389, https://doi.org/10.1016/j.neuron.2015.05.016.Search in Google Scholar

Kong, Q.M., Qiao, H., Liu, C.Z., Zhang, P., Li, K., Wang, L., Li, J.T., Su, Y., Li, K.Q., Yan, C.G., et al.. (2018). Aberrant intrinsic functional connectivity in thalamo-cortical networks in major depressive disorder. CNS Neurosci. Ther. 24: 1063–1072, https://doi.org/10.1111/cns.12831.Search in Google Scholar

Koutsikou, S., Watson, T.C., Crook, J.J., Leith, J.L., Lawrenson, C.L., Apps, R., and Lumb, B.M. (2015). The periaqueductal gray orchestrates sensory and motor circuits at multiple levels of the neuraxis. J. Neurosci. 35: 14132–14147, https://doi.org/10.1523/jneurosci.0261-15.2015.Search in Google Scholar

Krout, K.E., Jansen, A.S., and Loewy, A.D. (1998). Periaqueductal gray matter projection to the parabrachial nucleus in rat. J. Comp. Neurol. 401: 437–454, https://doi.org/10.1002/(sici)1096-9861(19981130)401:4<437::aid-cne2>3.0.co;2-5.10.1002/(SICI)1096-9861(19981130)401:4<437::AID-CNE2>3.0.CO;2-5Search in Google Scholar

Kuner, R. and Kuner, T. (2021). Cellular circuits in the brain and their modulation in acute and chronic pain. Physiol. Rev. 101: 213–258, https://doi.org/10.1152/physrev.00040.2019.Search in Google Scholar

Kwon, M., Altin, M., Duenas, H., and Alev, L. (2014). The role of descending inhibitory pathways on chronic pain modulation and clinical implications. Pain Pract. 14: 656–667, https://doi.org/10.1111/papr.12145.Search in Google Scholar

Lanius, R.A., Boyd, J.E., McKinnon, M.C., Nicholson, A.A., Frewen, P., Vermetten, E., Jetly, R., and Spiegel, D. (2018). A review of the neurobiological basis of trauma-related dissociation and its relation to cannabinoid- and opioid-mediated stress response: a transdiagnostic, translational approach. Curr. Psychiatry Rep. 20: 118, https://doi.org/10.1007/s11920-018-0983-y.Search in Google Scholar PubMed

Lau, B.K. and Vaughan, C.W. (2014). Descending modulation of pain: the GABA disinhibition hypothesis of analgesia. Curr. Opin. Neurobiol. 29: 159–164, https://doi.org/10.1016/j.conb.2014.07.010.Search in Google Scholar PubMed

Laubach, M., Amarante, L.M., Swanson, K., and White, S.R. (2018). What, if anything, is rodent prefrontal cortex? eNeuro 5: 5–6, https://doi.org/10.1523/eneuro.0315-18.2018.Search in Google Scholar PubMed PubMed Central

LeDoux, J. (2007). The amygdala. Curr. Biol. 17: R868–R874, https://doi.org/10.1016/j.cub.2007.08.005.Search in Google Scholar PubMed

Lee, J.Y., You, T., Lee, C.H., Im, G.H., Seo, H., Woo, C.W., and Kim, S.G. (2022). Role of anterior cingulate cortex inputs to periaqueductal gray for pain avoidance. Curr. Biol. 32: 2834–2847, https://doi.org/10.1016/j.cub.2022.04.090.Search in Google Scholar PubMed

Lenz, F.A., Weiss, N., Ohara, S., Lawson, C., and Greenspan, J.D. (2004). The role of the thalamus in pain. Suppl. Clin. Neurophysiol. 57: 50–61, https://doi.org/10.1016/s1567-424x(09)70342-3.Search in Google Scholar PubMed

Li, X.Y., Ko, H.G., Chen, T., Descalzi, G., Koga, K., Wang, H., Kim, S.S., Shang, Y., Kwak, C., Park, S.W., et al.. (2010). Alleviating neuropathic pain hypersensitivity by inhibiting PKMzeta in the anterior cingulate cortex. Science 330: 1400–1404, https://doi.org/10.1126/science.1191792.Search in Google Scholar PubMed

Liang, S.H., Zhao, W.J., Yin, J.B., Chen, Y.B., Li, J.N., Feng, B., Lu, Y.C., Wang, J., Dong, Y.L., and Li, Y.Q. (2020). A neural circuit from thalamic paraventricular nucleus to central amygdala for the facilitation of neuropathic pain. J. Neurosci. 40: 7837–7854, https://doi.org/10.1523/jneurosci.2487-19.2020.Search in Google Scholar

Llinás, R.R., Ribary, U., Jeanmonod, D., Kronberg, E., and Mitra, P.P. (1999). Thalamocortical dysrhythmia: a neurological and neuropsychiatric syndrome characterized by magnetoencephalography. Proc. Natl. Acad. Sci. U. S. A. 96: 15222–15227, https://doi.org/10.1073/pnas.96.26.15222.Search in Google Scholar PubMed PubMed Central

Loeser, J.D. and Melzack, R. (1999). Pain: an overview. Lancet 353: 1607–1609, https://doi.org/10.1016/s0140-6736(99)01311-2.Search in Google Scholar PubMed

Lu, C., Yang, T., Zhao, H., Zhang, M., Meng, F., Fu, H., Xie, Y., and Xu, H. (2016). Insular cortex is critical for the perception, modulation, and chronification of pain. Neurosci. Bull. 32: 191–201, https://doi.org/10.1007/s12264-016-0016-y.Search in Google Scholar PubMed PubMed Central

Luongo, L., de Novellis, V., Gatta, L., Palazzo, E., Vita, D., Guida, F., Giordano, C., Siniscalco, D., Marabese, I., De Chiaro, M., et al.. (2013). Role of metabotropic glutamate receptor 1 in the basolateral amygdala-driven prefrontal cortical deactivation in inflammatory pain in the rat. Neuropharmacology 66: 317–329, https://doi.org/10.1016/j.neuropharm.2012.05.047.Search in Google Scholar PubMed

Maihöfner, C. and Handwerker, H.O. (2005). Differential coding of hyperalgesia in the human brain: a functional MRI study. Neuroimage 28: 996–1006, https://doi.org/10.1016/j.neuroimage.2005.06.049.Search in Google Scholar PubMed

Mao, C.P., Yang, H.J., Yang, Q.X., Sun, H.H., Zhang, G.R., and Zhang, Q.J. (2022). Altered amygdala-prefrontal connectivity in chronic nonspecific low back pain: resting-state fMRI and dynamic causal modelling study. Neuroscience 482: 18–29, https://doi.org/10.1016/j.neuroscience.2021.12.003.Search in Google Scholar PubMed

Marek, R., Xu, L., Sullivan, R.K.P., and Sah, P. (2018). Excitatory connections between the prelimbic and infralimbic medial prefrontal cortex show a role for the prelimbic cortex in fear extinction. Nat. Neurosci. 21: 654–658, https://doi.org/10.1038/s41593-018-0137-x.Search in Google Scholar PubMed

Martenson, M.E., Cetas, J.S., and Heinricher, M.M. (2009). A possible neural basis for stress-induced hyperalgesia. Pain 142: 236–244, https://doi.org/10.1016/j.pain.2009.01.011.Search in Google Scholar PubMed PubMed Central

Matsumoto, N., Bester, H., Menendez, L., Besson, J.M., and Bernard, J.F. (1996). Changes in the responsiveness of parabrachial neurons in the arthritic rat: an electrophysiological study. J. Neurophysiol. 76: 4113–4126, https://doi.org/10.1152/jn.1996.76.6.4113.Search in Google Scholar PubMed

May, A. (2008). Chronic pain may change the structure of the brain. Pain 137: 7–15, https://doi.org/10.1016/j.pain.2008.02.034.Search in Google Scholar PubMed

May, A. (2011). Structural brain imaging: a window into chronic pain. Neuroscientist 17: 209–220, https://doi.org/10.1177/1073858410396220.Search in Google Scholar PubMed

Mazzitelli, M., Marshall, K., Pham, A., Ji, G., and Neugebauer, V. (2021). Optogenetic manipulations of amygdala neurons modulate spinal nociceptive processing and behavior under normal conditions and in an arthritis pain model. Front. Pharmacol. 12: 668337, https://doi.org/10.3389/fphar.2021.668337.Search in Google Scholar PubMed PubMed Central

Mazzitelli, M., Yakhnitsa, V., Neugebauer, B., and Neugebauer, V. (2022). Optogenetic manipulations of CeA-CRF neurons modulate pain- and anxiety-like behaviors in neuropathic pain and control rats. Neuropharmacology 210: 109031, https://doi.org/10.1016/j.neuropharm.2022.109031.Search in Google Scholar PubMed PubMed Central

Mazzola, L., Isnard, J., Peyron, R., Guénot, M., and Mauguière, F. (2009). Somatotopic organization of pain responses to direct electrical stimulation of the human insular cortex. Pain 146: 99–104, https://doi.org/10.1016/j.pain.2009.07.014.Search in Google Scholar PubMed

McPherson, K.B. and Ingram, S.L. (2022). Cellular and circuit diversity determines the impact of endogenous opioids in the descending pain modulatory pathway. Front. Syst. Neurosci. 16: 963812, https://doi.org/10.3389/fnsys.2022.963812.Search in Google Scholar PubMed PubMed Central

Meda, K.S., Patel, T., Braz, J.M., Malik, R., Turner, M.L., Seifikar, H., Basbaum, A.I., and Sohal, V.S. (2019). Microcircuit mechanisms through which mediodorsal thalamic input to anterior cingulate cortex exacerbates pain-related aversion. Neuron 102: 944–959, https://doi.org/10.1016/j.neuron.2019.03.042.Search in Google Scholar PubMed PubMed Central

Melzack, R. (1999). From the gate to the neuromatrix. Pain (Suppl. 6) 3: S121–S26, https://doi.org/10.1016/s0304-3959(99)00145-1.Search in Google Scholar PubMed

Melzack, R. (2001). Pain and the neuromatrix in the brain. J Dent Educ 65: 1378–1382, https://doi.org/10.1002/j.0022-0337.2001.65.12.tb03497.x.Search in Google Scholar

Meng, X., Yue, L., Liu, A., Tao, W., Shi, L., Zhao, W., Wu, Z., Zhang, Z., Wang, L., Zhang, X., et al.. (2022). Distinct basolateral amygdala excitatory inputs mediate the somatosensory and aversive-affective components of pain. J. Biol. Chem. 298: 102207, https://doi.org/10.1016/j.jbc.2022.102207.Search in Google Scholar PubMed PubMed Central

Millan, M.J. (2002). Descending control of pain. Prog. Neurobiol. 66: 355–474, https://doi.org/10.1016/s0301-0082(02)00009-6.Search in Google Scholar PubMed

Miller Neilan, R., Majetic, G., Gil-Silva, M., Adke, A.P., Carrasquillo, Y., and Kolber, B.J. (2021). Agent-based modeling of the central amygdala and pain using cell-type specific physiological parameters. PLoS Comput. Biol. 17: e1009097, https://doi.org/10.1371/journal.pcbi.1009097.Search in Google Scholar PubMed PubMed Central

Monroe, T.B., Fillingim, R.B., Bruehl, S.P., Rogers, B.P., Dietrich, M.S., Gore, J.C., Atalla, S.W., and Cowan, R.L. (2018). Sex differences in brain regions modulating pain among older adults: a cross-sectional resting state functional connectivity study. Pain Med. 19: 1737–1747, https://doi.org/10.1093/pm/pnx084.Search in Google Scholar PubMed PubMed Central

Morgan, M.M. and Fields, H.L. (1994). Pronounced changes in the activity of nociceptive modulatory neurons in the rostral ventromedial medulla in response to prolonged thermal noxious stimuli. J. Neurophysiol. 72: 1161–1170, https://doi.org/10.1152/jn.1994.72.3.1161.Search in Google Scholar PubMed

Morton, D.L., Sandhu, J.S., and Jones, A.K. (2016). Brain imaging of pain: state of the art. J. Pain Res. 9: 613–624, https://doi.org/10.2147/jpr.s60433.Search in Google Scholar PubMed PubMed Central

Mukherjee, A. and Caroni, P. (2019). Author correction: infralimbic cortex is required for learning alternatives to prelimbic promoted associations through reciprocal connectivity. Nat. Commun. 10: 3082, https://doi.org/10.1038/s41467-019-11205-w.Search in Google Scholar PubMed PubMed Central

Nagasaka, K., Takashima, I., Matsuda, K., and Higo, N. (2017). Late-onset hypersensitivity after a lesion in the ventral posterolateral nucleus of the thalamus: a macaque model of central post-stroke pain. Sci. Rep. 7: 10316, https://doi.org/10.1038/s41598-017-10679-2.Search in Google Scholar PubMed PubMed Central

Nardone, R., Höller, Y., Sebastianelli, L., Versace, V., Saltuari, L., Brigo, F., Lochner, P., and Trinka, E. (2018). Cortical morphometric changes after spinal cord injury. Brain Res. Bull. 137: 107–119, https://doi.org/10.1016/j.brainresbull.2017.11.013.Search in Google Scholar PubMed

Neubert, M.J., Kincaid, W., and Heinricher, M.M. (2004). Nociceptive facilitating neurons in the rostral ventromedial medulla. Pain 110: 158–165, https://doi.org/10.1016/j.pain.2004.03.017.Search in Google Scholar PubMed

Neugebauer, V. (2020). Amygdala physiology in pain. Handb. Behav. Neurosci. 26: 101–113, https://doi.org/10.1016/b978-0-12-815134-1.00004-0.Search in Google Scholar PubMed PubMed Central

Neugebauer, V., Li, W., Bird, G.C., and Han, J.S. (2004). The amygdala and persistent pain. Neuroscientist 10: 221–234, https://doi.org/10.1177/1073858403261077.Search in Google Scholar PubMed

Neugebauer, V., Mazzitelli, M., Cragg, B., Ji, G., Navratilova, E., and Porreca, F. (2020). Amygdala, neuropeptides, and chronic pain-related affective behaviors. Neuropharmacology 170: 108052, https://doi.org/10.1016/j.neuropharm.2020.108052.Search in Google Scholar PubMed PubMed Central

Neumann, L., Wulms, N., Witte, V., Spisak, T., Zunhammer, M., Bingel, U., and Schmidt-Wilcke, T. (2021). Network properties and regional brain morphology of the insular cortex correlate with individual pain thresholds. Hum. Brain Mapp. 42: 4896–4908, https://doi.org/10.1002/hbm.25588.Search in Google Scholar PubMed PubMed Central

Nguyen, E., Smith, K.M., Cramer, N., Holland, R.A., Bleimeister, I.H., Flores-Felix, K., Silberberg, H., Keller, A., Le Pichon, C.E., and Ross, S.E. (2022). Medullary kappa-opioid receptor neurons inhibit pain and itch through a descending circuit. Brain 145: 2586–2601, https://doi.org/10.1093/brain/awac189.Search in Google Scholar PubMed PubMed Central

Okada, T., Kato, D., Nomura, Y., Obata, N., Quan, X., Morinaga, A., Yano, H., Guo, Z., Aoyama, Y., Tachibana, Y., et al. (2021). Pain induces stable, active microcircuits in the somatosensory cortex that provide a therapeutic target. Sci. Adv. 7: 6–8, https://doi.org/10.1126/sciadv.abd8261.Search in Google Scholar PubMed PubMed Central

Osborne, N.R., Cheng, J.C., Rogachov, A., Kim, J.A., Hemington, K.S., Bosma, R.L., Inman, R.D., and Davis, K.D. (2021). Abnormal subgenual anterior cingulate circuitry is unique to women but not men with chronic pain. Pain 162: 97–108, https://doi.org/10.1097/j.pain.0000000000002016.Search in Google Scholar PubMed

Ossipov, M.H., Dussor, G.O., and Porreca, F. (2010). Central modulation of pain. J. Clin. Invest. 120: 3779–3787, https://doi.org/10.1172/jci43766.Search in Google Scholar

Ossipov, M.H., Morimura, K., and Porreca, F. (2014). Descending pain modulation and chronification of pain. Curr. Opin. Support Palliat. Care 8: 143–151, https://doi.org/10.1097/spc.0000000000000055.Search in Google Scholar

Ostrowsky, K., Magnin, M., Ryvlin, P., Isnard, J., Guenot, M., and Mauguière, F. (2002). Representation of pain and somatic sensation in the human insula: a study of responses to direct electrical cortical stimulation. Cereb. Cortex 12: 376–385, https://doi.org/10.1093/cercor/12.4.376.Search in Google Scholar PubMed

Otsu, Y. and Aubrey, K.R. (2022). Kappa opioids inhibit the GABA/glycine terminals of rostral ventromedial medulla projections in the superficial dorsal horn of the spinal cord. J. Physiol. 600: 4187–4205, https://doi.org/10.1113/jp283021.Search in Google Scholar

Pare, D. and Duvarci, S. (2012). Amygdala microcircuits mediating fear expression and extinction. Curr. Opin. Neurobiol. 22: 717–723, https://doi.org/10.1016/j.conb.2012.02.014.Search in Google Scholar PubMed PubMed Central

Pauli, J.L., Chen, J.Y., Basiri, M.L., Park, S., Carter, M.E., Sanz, E., McKnight, G.S., Stuber, G.D., and Palmiter, R.D. (2022). Molecular and anatomical characterization of parabrachial neurons and their axonal projections. Elife 11: 5–7.10.7554/eLife.81868Search in Google Scholar PubMed PubMed Central

Peyron, R., Laurent, B., and García-Larrea, L. (2000). Functional imaging of brain responses to pain. A review and meta-analysis (2000), Neurophysiol. Clin. 30: 263–288, https://doi.org/10.1016/s0987-7053(00)00227-6.Search in Google Scholar PubMed

Pieretti, S., Di Giannuario, A., Di Giovannandrea, R., Marzoli, F., Piccaro, G., Minosi, P., and Aloisi, A.M. (2016). Gender differences in pain and its relief. Ann. Ist. Super Sanita. 52: 184–189, https://doi.org/10.4415/ANN_16_02_09.Search in Google Scholar PubMed

Ploghaus, A., Tracey, I., Gati, J.S., Clare, S., Menon, R.S., Matthews, P.M., and Rawlins, J.N. (1999). Dissociating pain from its anticipation in the human brain. Science 284: 1979–1981, https://doi.org/10.1126/science.284.5422.1979.Search in Google Scholar PubMed

Ploner, M., Schmitz, F., Freund, H.J., and Schnitzler, A. (2000). Differential organization of touch and pain in human primary somatosensory cortex. J. Neurophysiol. 83: 1770–1776, https://doi.org/10.1152/jn.2000.83.3.1770.Search in Google Scholar PubMed

Presto, P. and Neugebauer, V. (2022). Sex differences in CGRP regulation and function in the amygdala in a rat model of neuropathic pain. Front. Mol. Neurosci. 15: 928587, https://doi.org/10.3389/fnmol.2022.928587.Search in Google Scholar PubMed PubMed Central

Raja, S.N., Carr, D.B., Cohen, M., Finnerup, N.B., Flor, H., Gibson, S., Keefe, F.J., Mogil, J.S., Ringkamp, M., Sluka, K.A., et al.. (2020). The revised International Association for the Study of Pain definition of pain: concepts, challenges, and compromises. Pain 161: 1976–1982, https://doi.org/10.1097/j.pain.0000000000001939.Search in Google Scholar PubMed PubMed Central

Raver, C., Uddin, O., Ji, Y., Li, Y., Cramer, N., Jenne, C., Morales, M., Masri, R., and Keller, A. (2020). An amygdalo-parabrachial pathway regulates pain perception and chronic pain. J. Neurosci. 40: 3424–3442, https://doi.org/10.1523/jneurosci.0075-20.2020.Search in Google Scholar

Ren, J., Xiang, J., Chen, Y., Li, F., Wu, T., and Shi, J. (2019). Abnormal functional connectivity under somatosensory stimulation in migraine: a multi-frequency magnetoencephalography study. J. Headache Pain 20: 3, https://doi.org/10.1186/s10194-019-0958-3.Search in Google Scholar PubMed PubMed Central

Roeder, Z., Chen, Q., Davis, S., Carlson, J.D., Tupone, D., and Heinricher, M.M. (2016). Parabrachial complex links pain transmission to descending pain modulation. Pain 157: 2697–2708, https://doi.org/10.1097/j.pain.0000000000000688.Search in Google Scholar PubMed PubMed Central

Rosenfeld, M.G., Mermod, J.J., Amara, S.G., Swanson, L.W., Sawchenko, P.E., Rivier, J., Vale, W.W., and Evans, R.M. (1983). Production of a novel neuropeptide encoded by the calcitonin gene via tissue-specific RNA processing. Nature 304: 129–135, https://doi.org/10.1038/304129a0.Search in Google Scholar PubMed

Saadé, N.E., Al Amin, H., Abdel Baki, S., Safieh-Garabedian, B., Atweh, S.F., and Jabbur, S.J. (2006). Transient attenuation of neuropathic manifestations in rats following lesion or reversible block of the lateral thalamic somatosensory nuclei. Exp. Neurol. 197: 157–166, https://doi.org/10.1016/j.expneurol.2005.09.005.Search in Google Scholar PubMed

Sadler, K.E., McQuaid, N.A., Cox, A.C., Behun, M.N., Trouten, A.M., and Kolber, B.J. (2017). Divergent functions of the left and right central amygdala in visceral nociception. Pain 158: 747–759, https://doi.org/10.1097/j.pain.0000000000000830.Search in Google Scholar PubMed PubMed Central

Sah, P., Faber, E.S., Lopez De Armentia, M., and Power, J. (2003). The amygdaloid complex: anatomy and physiology. Physiol. Rev. 83: 803–834, https://doi.org/10.1152/physrev.00002.2003.Search in Google Scholar PubMed

Samineni, V.K., Grajales-Reyes, J.G., Copits, B.A., O’Brien, D.E., Trigg, S.L., Gomez, A.M., Bruchas, M.R., and Gereau, R.W.th. (2017). Divergent modulation of nociception by glutamatergic and GABAergic neuronal subpopulations in the periaqueductal gray. eNeuro 4: 4–9, https://doi.org/10.1523/eneuro.0129-16.2017.Search in Google Scholar

Santello, M. and Nevian, T. (2015). Dysfunction of cortical dendritic integration in neuropathic pain reversed by serotoninergic neuromodulation. Neuron 86: 233–246, https://doi.org/10.1016/j.neuron.2015.03.003.Search in Google Scholar PubMed

Saper, C.B. and Loewy, A.D. (2016). Commentary on: efferent connections of the parabrachial nucleus in the rat. C.B. Saper and A.D. Loewy, Brain Research 197: 291–317, 1980. Brain Res. 197: 1645: 15–7. https://doi.org/10.1016/0006-8993(80)91117-8.Search in Google Scholar PubMed

Schnitzler, A. and Ploner, M. (2000). Neurophysiology and functional neuroanatomy of pain perception. J. Clin. Neurophysiol. 17: 592–603, https://doi.org/10.1097/00004691-200011000-00005.Search in Google Scholar PubMed

Segerdahl, A.R., Mezue, M., Okell, T.W., Farrar, J.T., and Tracey, I. (2015). The dorsal posterior insula subserves a fundamental role in human pain. Nat. Neurosci. 18: 499–500, https://doi.org/10.1038/nn.3969.Search in Google Scholar PubMed PubMed Central

Sellmeijer, J., Mathis, V., Hugel, S., Li, X.H., Song, Q., Chen, Q.Y., Barthas, F., Lutz, P.E., Karatas, M., Luthi, A., et al.. (2018). Hyperactivity of anterior cingulate cortex areas 24a/24b drives chronic pain-induced anxiodepressive-like consequences. J. Neurosci. 38: 3102–3115, https://doi.org/10.1523/jneurosci.3195-17.2018.Search in Google Scholar PubMed PubMed Central

Seminowicz, D.A. and Moayedi, M. (2017). The dorsolateral prefrontal cortex in acute and chronic pain. J. Pain 18: 1027–1035, https://doi.org/10.1016/j.jpain.2017.03.008.Search in Google Scholar PubMed PubMed Central

Senn, V., Wolff, S.B., Herry, C., Grenier, F., Ehrlich, I., Gründemann, J., Fadok, J.P., Müller, C., Letzkus, J.J., and Lüthi, A. (2014). Long-range connectivity defines behavioral specificity of amygdala neurons. Neuron 81: 428–437, https://doi.org/10.1016/j.neuron.2013.11.006.Search in Google Scholar PubMed

Shinohara, K., Watabe, A.M., Nagase, M., Okutsu, Y., Takahashi, Y., Kurihara, H., and Kato, F. (2017). Essential role of endogenous calcitonin gene-related peptide in pain-associated plasticity in the central amygdala. Eur. J. Neurosci. 46: 2149–2160, https://doi.org/10.1111/ejn.13662.Search in Google Scholar PubMed PubMed Central

Singer, T., Critchley, H.D., and Preuschoff, K. (2009). A common role of insula in feelings, empathy and uncertainty. Trends Cogn. Sci. 13: 334–340, https://doi.org/10.1016/j.tics.2009.05.001.Search in Google Scholar PubMed

Singh, A., Patel, D., Li, A., Hu, L., Zhang, Q., Liu, Y., Guo, X., Robinson, E., Martinez, E., Doan, L., et al.. (2020). Mapping cortical integration of sensory and affective pain pathways. Curr. Biol. 30: 1703–1715, https://doi.org/10.1016/j.cub.2020.02.091.Search in Google Scholar PubMed PubMed Central

Sun, L., Liu, R., Guo, F., Wen, M.Q., Ma, X.L., Li, K.Y., Sun, H., Xu, C.L., Li, Y.Y., Wu, M.Y., et al.. (2020a). Parabrachial nucleus circuit governs neuropathic pain-like behavior. Nat. Commun. 11: 5974, https://doi.org/10.1038/s41467-020-19767-w.Search in Google Scholar PubMed PubMed Central

Sun, Y., Wang, J., Liang, S.H., Ge, J., Lu, Y.C., Li, J.N., Chen, Y.B., Luo, D.S., Li, H., and Li, Y.Q. (2020b). Involvement of the ventrolateral periaqueductal gray matter-central medial thalamic nucleus-basolateral amygdala pathway in neuropathic pain regulation of rats. Front. Neuroanat. 14: 32, https://doi.org/10.3389/fnana.2020.00032.Search in Google Scholar PubMed PubMed Central

Tan, L.L., Oswald, M.J., Heinl, C., Retana Romero, O.A., Kaushalya, S.K., Monyer, H., and Kuner, R. (2019). Gamma oscillations in somatosensory cortex recruit prefrontal and descending serotonergic pathways in aversion and nociception. Nat. Commun. 10: 983, https://doi.org/10.1038/s41467-019-08873-z.Search in Google Scholar PubMed PubMed Central

Tang, J.S., Chiang, C.Y., Dostrovsky, J.O., Yao, D., and Sessle, B.J. (2021). Responses of neurons in rostral ventromedial medulla to nociceptive stimulation of craniofacial region and tail in rats. Brain Res. 1767: 147539, https://doi.org/10.1016/j.brainres.2021.147539.Search in Google Scholar PubMed PubMed Central

Taylor, N.E., Pei, J., Zhang, J., Vlasov, K.Y., Davis, T., Taylor, E., Weng, F.J., Van Dort, C.J., Solt, K., and Brown, E.N. (2019). The role of glutamatergic and dopaminergic neurons in the periaqueductal gray/dorsal raphe: separating analgesia and anxiety. eNeuro 6: 4–10.10.1523/ENEURO.0018-18.2019Search in Google Scholar PubMed PubMed Central

Thompson, J.M. and Neugebauer, V. (2017). Amygdala plasticity and pain. Pain Res. Manag. 2017: 829650110.1155/2017/8296501Search in Google Scholar PubMed PubMed Central

Thompson, J.M. and Neugebauer, V. (2019). Cortico-limbic pain mechanisms. Neurosci. Lett. 702: 15–23, https://doi.org/10.1016/j.neulet.2018.11.037.Search in Google Scholar PubMed PubMed Central

Tian, Y. and Zalesky, A. (2018). Characterizing the functional connectivity diversity of the insula cortex: subregions, diversity curves and behavior. Neuroimage 183: 716–733, https://doi.org/10.1016/j.neuroimage.2018.08.055.Search in Google Scholar PubMed

Timmermann, L., Ploner, M., Haucke, K., Schmitz, F., Baltissen, R., and Schnitzler, A. (2001). Differential coding of pain intensity in the human primary and secondary somatosensory cortex. J. Neurophysiol. 86: 1499–1503, https://doi.org/10.1152/jn.2001.86.3.1499.Search in Google Scholar PubMed

Tobaldini, G., Sardi, N.F., Guilhen, V.A., and Fischer, L. (2019). Pain inhibits pain: an ascending-descending pain modulation pathway linking mesolimbic and classical descending mechanisms. Mol. Neurobiol. 56: 1000–1013, https://doi.org/10.1007/s12035-018-1116-7.Search in Google Scholar PubMed

Todd, A.J. (2010). Neuronal circuitry for pain processing in the dorsal horn. Nat. Rev. Neurosci. 11: 823–836, https://doi.org/10.1038/nrn2947.Search in Google Scholar PubMed PubMed Central

Tonsfeldt, K.J., Suchland, K.L., Beeson, K.A., Lowe, J.D., Li, M.H., and Ingram, S.L. (2016). Sex differences in GABAA signaling in the periaqueductal gray induced by persistent inflammation. J. Neurosci. 36: 1669–1681, https://doi.org/10.1523/jneurosci.1928-15.2016.Search in Google Scholar

Tovote, P., Esposito, M.S., Botta, P., Chaudun, F., Fadok, J.P., Markovic, M., Wolff, S.B., Ramakrishnan, C., Fenno, L., Deisseroth, K., et al.. (2016). Midbrain circuits for defensive behaviour. Nature 534: 206–212, https://doi.org/10.1038/nature17996.Search in Google Scholar PubMed

Tracey, I. (2005). Nociceptive processing in the human brain. Curr. Opin. Neurobiol. 15: 478–487, https://doi.org/10.1016/j.conb.2005.06.010.Search in Google Scholar PubMed

Uddin, O., Studlack, P., Akintola, T., Raver, C., Castro, A., Masri, R., and Keller, A. (2018). Amplified parabrachial nucleus activity in a rat model of trigeminal neuropathic pain. Neurobiol. Pain 3: 22–30, https://doi.org/10.1016/j.ynpai.2018.02.002.Search in Google Scholar PubMed PubMed Central

Vachon-Presseau, E., Tétreault, P., Petre, B., Huang, L., Berger, S.E., Torbey, S., Baria, A.T., Mansour, A.R., Hashmi, J.A., Griffith, J.W., et al.. (2016). Corticolimbic anatomical characteristics predetermine risk for chronic pain. Brain 139: 1958–1970, https://doi.org/10.1093/brain/aww100.Search in Google Scholar PubMed PubMed Central

Veinante, P., Yalcin, I., and Barrot, M. (2013). The amygdala between sensation and affect: a role in pain. J. Mol. Psychiatry 1: 9, https://doi.org/10.1186/2049-9256-1-9.Search in Google Scholar PubMed PubMed Central

Veréb, D., Kincses, B., Spisák, T., Schlitt, F., Szabó, N., Faragó, P., Kocsis, K., Bozsik, B., Tóth, E., Király, A., et al.. (2021). Resting-state functional heterogeneity of the right insula contributes to pain sensitivity. Sci. Rep. 11: 22945, https://doi.org/10.1038/s41598-021-02474-x.Search in Google Scholar PubMed PubMed Central

Vertes, R.P. (2004). Differential projections of the infralimbic and prelimbic cortex in the rat. Synapse 51: 32–58, https://doi.org/10.1002/syn.10279.Search in Google Scholar PubMed

Vertes, R.P. (2006). Interactions among the medial prefrontal cortex, hippocampus and midline thalamus in emotional and cognitive processing in the rat. Neuroscience 142: 1–20, https://doi.org/10.1016/j.neuroscience.2006.06.027.Search in Google Scholar PubMed

Wang, G., Erpelding, N., and Davis, K.D. (2014). Sex differences in connectivity of the subgenual anterior cingulate cortex. Pain 155: 755–763, https://doi.org/10.1016/j.pain.2014.01.005.Search in Google Scholar PubMed

Wang, G.Q., Cen, C., Li, C., Cao, S., Wang, N., Zhou, Z., Liu, X.M., Xu, Y., Tian, N.X., Zhang, Y., et al.. (2015). Deactivation of excitatory neurons in the prelimbic cortex via Cdk5 promotes pain sensation and anxiety. Nat. Commun. 6: 7660, https://doi.org/10.1038/ncomms8660.Search in Google Scholar PubMed PubMed Central

Wang, N., Zhang, Y.H., Wang, J.Y., and Luo, F. (2021). Current understanding of the involvement of the insular cortex in neuropathic pain: a narrative review. Int. J. Mol. Sci. 22: 2648, https://doi.org/10.3390/ijms22052648.Search in Google Scholar PubMed PubMed Central

Wang, W., Tang, S., Li, C., Chen, J., Li, H., Su, Y., and Ning, B. (2019). Specific brain morphometric changes in spinal cord injury: a voxel-based meta-analysis of white and gray matter volume. J. Neurotrauma 36: 2348–2357, https://doi.org/10.1089/neu.2018.6205.Search in Google Scholar PubMed

Wang, Z., Huang, S., Yu, X., Li, L., Yang, M., Liang, S., Liu, W., and Tao, J. (2020). Altered thalamic neurotransmitters metabolism and functional connectivity during the development of chronic constriction injury induced neuropathic pain. Biol. Res. 53: 36, https://doi.org/10.1186/s40659-020-00303-5.Search in Google Scholar PubMed PubMed Central

Wiech, K. and Tracey, I. (2009). The influence of negative emotions on pain: behavioral effects and neural mechanisms. Neuroimage 47: 987–994, https://doi.org/10.1016/j.neuroimage.2009.05.059.Search in Google Scholar PubMed

Willis, W.D. and Westlund, K.N. (1997). Neuroanatomy of the pain system and of the pathways that modulate pain. J. Clin. Neurophysiol. 14: 2–31, https://doi.org/10.1097/00004691-199701000-00002.Search in Google Scholar PubMed PubMed Central

Wilson, T.D., Valdivia, S., Khan, A., Ahn, H.S., Adke, A.P., Martinez Gonzalez, S., Sugimura, Y.K., and Carrasquillo, Y. (2019). Dual and opposing functions of the central amygdala in the modulation of pain. Cell Rep. 29: 332–346, https://doi.org/10.1016/j.celrep.2019.09.011.Search in Google Scholar PubMed PubMed Central

Wong, C.E., Hu, C.Y., Lee, P.H., Huang, C.C., Huang, H.W., Huang, C.Y., Lo, H.T., Liu, W., and Lee, J.S. (2022). Sciatic nerve stimulation alleviates acute neuropathic pain via modulation of neuroinflammation and descending pain inhibition in a rodent model. J. Neuroinflammation 19: 153, https://doi.org/10.1186/s12974-022-02513-y.Search in Google Scholar PubMed PubMed Central

Woon, E.P., Sequeira, M.K., Barbee, B.R., and Gourley, S.L. (2020). Involvement of the rodent prelimbic and medial orbitofrontal cortices in goal-directed action: a brief review. J. Neurosci. Res. 98: 1020–1030, https://doi.org/10.1002/jnr.24567.Search in Google Scholar PubMed PubMed Central

Worthen, S.F., Hobson, A.R., Hall, S.D., Aziz, Q., and Furlong, P.L. (2011). Primary and secondary somatosensory cortex responses to anticipation and pain: a magnetoencephalography study. Eur. J. Neurosci. 33: 946–959, https://doi.org/10.1111/j.1460-9568.2010.07575.x.Search in Google Scholar PubMed

Yalcin, I., Barthas, F., and Barrot, M. (2014). Emotional consequences of neuropathic pain: insight from preclinical studies. Neurosci. Biobehav. Rev. 47: 154–164, https://doi.org/10.1016/j.neubiorev.2014.08.002.Search in Google Scholar PubMed

Yin, J.B., Liang, S.H., Li, F., Zhao, W.J., Bai, Y., Sun, Y., Wu, Z.Y., Ding, T., Sun, Y., Liu, H.X., et al.. (2020). dmPFC-vlPAG projection neurons contribute to pain threshold maintenance and antianxiety behaviors. J. Clin. Invest. 130: 6555–6570, https://doi.org/10.1172/jci127607.Search in Google Scholar

Yu, W., Pati, D., Pina, M.M., Schmidt, K.T., Boyt, K.M., Hunker, A.C., Zweifel, L.S., McElligott, Z.A., and Kash, T.L. (2021). Periaqueductal gray/dorsal raphe dopamine neurons contribute to sex differences in pain-related behaviors. Neuron 109: 1365–1380, https://doi.org/10.1016/j.neuron.2021.03.001.Search in Google Scholar PubMed PubMed Central

Yue, L., Ma, L.Y., Cui, S., Liu, F.Y., Yi, M., and Wan, Y. (2017). Brain-derived neurotrophic factor in the infralimbic cortex alleviates inflammatory pain. Neurosci. Lett. 655: 7–13, https://doi.org/10.1016/j.neulet.2017.06.028.Search in Google Scholar PubMed

Zhang, C., Chen, R.X., Zhang, Y., Wang, J., Liu, F.Y., Cai, J., Liao, F.F., Xu, F.Q., Yi, M., and Wan, Y. (2017). Reduced GABAergic transmission in the ventrobasal thalamus contributes to thermal hyperalgesia in chronic inflammatory pain. Sci. Rep. 7: 41439, https://doi.org/10.1038/srep41439.Search in Google Scholar PubMed PubMed Central

Zhang, M.M., Geng, A.Q., Chen, K., Wang, J., Wang, P., Qiu, X.T., Gu, J.X., Fan, H.W., Zhu, D.Y., Yang, S.M., et al.. (2022). Glutamatergic synapses from the insular cortex to the basolateral amygdala encode observational pain. Neuron 110: 1993–2008, https://doi.org/10.1016/j.neuron.2022.03.030.Search in Google Scholar PubMed

Zhang, Z., Gadotti, V.M., Chen, L., Souza, I.A., Stemkowski, P.L., and Zamponi, G.W. (2015). Role of prelimbic GABAergic circuits in sensory and emotional aspects of neuropathic pain. Cell Rep. 12: 752–759, https://doi.org/10.1016/j.celrep.2015.07.001.Search in Google Scholar PubMed

Zhou, H., Zhang, Q., Martinez, E., Dale, J., Hu, S., Zhang, E., Liu, K., Huang, D., Yang, G., Chen, Z., et al.. (2018). Ketamine reduces aversion in rodent pain models by suppressing hyperactivity of the anterior cingulate cortex. Nat. Commun. 9: 3751, https://doi.org/10.1038/s41467-018-06295-x.Search in Google Scholar PubMed PubMed Central

Zhu, H., Xiang, H.C., Li, H.P., Lin, L.X., Hu, X.F., Zhang, H., Meng, W.Y., Liu, L., Chen, C., Shu, Y., et al.. (2019). Inhibition of GABAergic neurons and excitation of glutamatergic neurons in the ventrolateral periaqueductal gray participate in electroacupuncture analgesia mediated by cannabinoid receptor. Front. Neurosci. 13: 484, https://doi.org/10.3389/fnins.2019.00484.Search in Google Scholar PubMed PubMed Central

Zhu, X., Xu, Y., Shen, Z., Zhang, H., Xiao, S., Zhu, Y., Wu, M., Chen, Y., Wu, Z., Xu, Y., et al.. (2021). Rostral anterior cingulate cortex-ventrolateral periaqueductal gray circuit underlies electroacupuncture to alleviate hyperalgesia but not anxiety-like behaviors in mice with spared nerve injury. Front. Neurosci. 15: 757628, https://doi.org/10.3389/fnins.2021.757628.Search in Google Scholar PubMed PubMed Central

Zhu, X., Zhou, W., Jin, Y., Tang, H., Cao, P., Mao, Y., Xie, W., Zhang, X., Zhao, F., Luo, M.H., et al.. (2019). A central amygdala input to the parafascicular nucleus controls comorbid pain in depression. Cell Rep. 29: 3847–3858, https://doi.org/10.1016/j.celrep.2019.11.003.Search in Google Scholar PubMed PubMed Central

Zhu, Y.B., Wang, Y., Hua, X.X., Xu, L., Liu, M.Z., Zhang, R., Liu, P.F., Li, J.B., Zhang, L., and Mu, D. (2022). PBN-PVT projections modulate negative affective states in mice. Elife 11: 6–9, https://doi.org/10.7554/elife.68372.Search in Google Scholar

Zhuo, M. and Gebhart, G.F. (1997). Biphasic modulation of spinal nociceptive transmission from the medullary raphe nuclei in the rat. J. Neurophysiol. 78: 746–758, https://doi.org/10.1152/jn.1997.78.2.746.Search in Google Scholar PubMed

Received: 2023-03-25
Accepted: 2023-05-18
Published Online: 2023-06-08
Published in Print: 2023-12-15

© 2023 Walter de Gruyter GmbH, Berlin/Boston

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