Nature Neuroscience

Somatosensory cortex and central amygdala regulate neuropathic pain-mediated peripheral immune response via vagal projections to the spleen

  • Gao, X. et al. Nociceptive nerves regulate haematopoietic stem cell mobilization. Nature 589, 591–596 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kuner, R. & Kuner, T. Cellular circuits in the brain and their modulation in acute and chronic pain. Physiol. Rev. 101, 213–258 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Grace, P. M., Hutchinson, M. R., Maier, S. F. & Watkins, L. R. Pathological pain and the neuroimmune interface. Nat. Rev. Immunol. 14, 217–231 (2014).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Baral, P., Udit, S. & Chiu, I. M. Pain and immunity: implications for host defence. Nat. Rev. Immunol. 19, 433–447 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ji, R. R., Chamessian, A. & Zhang, Y. Q. Pain regulation by non-neuronal cells and inflammation. Science 354, 572–577 (2016).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mohanta, S. K. et al. Neuroimmune cardiovascular interfaces control atherosclerosis. Nature 605, 152–159 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chiu, I. M., von Hehn, C. A. & Woolf, C. J. Neurogenic inflammation and the peripheral nervous system in host defense and immunopathology. Nat. Neurosci. 15, 1063–1067 (2012).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, S. et al. A neuroanatomical basis for electroacupuncture to drive the vagal-adrenal axis. Nature 598, 641–645 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tanaka, S. et al. Vagus nerve stimulation activates two distinct neuroimmune circuits converging in the spleen to protect mice from kidney injury. Proc. Natl Acad. Sci. USA 118, e2021758118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Xu, Y. et al. Pituitary hormone α-MSH promotes tumor-induced myelopoiesis and immunosuppression. Science 377, 1085–1091 (2022).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bassi, G. S. et al. Anatomical and clinical implications of vagal modulation of the spleen. Neurosci. Biobehav. Rev. 112, 363–373 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Liu, D. et al. CD97 promotes spleen dendritic cell homeostasis through the mechanosensing of red blood cells. Science 375, eabi5965 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Verlinden, T. J. M. et al. Innervation of the human spleen: a complete hilum-embedding approach. Brain Behav. Immun. 77, 92–100 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Schiller, M., Ben-Shaanan, T. L. & Rolls, A. Neuronal regulation of immunity: why, how and where? Nat. Rev. Immunol. 21, 20–36 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Veerakumar, A., Yung, A. R., Liu, Y. & Krasnow, M. A. Molecularly defined circuits for cardiovascular and cardiopulmonary control. Nature 606, 739–746 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaelberer, M. M., Rupprecht, L. E., Liu, W. W., Weng, P. & Bohorquez, D. V. Neuropod cells: the emerging biology of gut-brain sensory transduction. Annu. Rev. Neurosci. 43, 337–353 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Pavlov, V. A. & Tracey, K. J. Neural regulation of immunity: molecular mechanisms and clinical translation. Nat. Neurosci. 20, 156–166 (2017).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Okusa, M. D., Rosin, D. L. & Tracey, K. J. Targeting neural reflex circuits in immunity to treat kidney disease. Nat. Rev. Nephrol. 13, 669–680 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Winkelmann, A., Loebermann, M., Barnett, M., Hartung, H. P. & Zettl, U. K. Vaccination and immunotherapies in neuroimmunological diseases. Nat. Rev. Neurol. 18, 289–306 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Tracey, K. J. The inflammatory reflex. Nature 420, 853–859 (2002).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Hu, B. et al. γδT cells and adipocyte IL-17RC control fat innervation and thermogenesis. Nature 578, 610–614 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kaelberer, M. M. et al. A gut–brain neural circuit for nutrient sensory transduction. Science 361, eaat5236 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Borovikova, L. V. et al. Vagus nerve stimulation attenuates the systemic inflammatory response to endotoxin. Nature 405, 458–462 (2000).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Kressel, A. M. et al. Identification of a brainstem locus that inhibits tumor necrosis factor. Proc. Natl Acad. Sci. USA 117, 29803–29810 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Cailotto, C. et al. Neuroanatomical evidence demonstrating the existence of the vagal anti-inflammatory reflex in the intestine. Neurogastroenterol. Motil. 24, 191–200 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Chavan, S. S., Pavlov, V. A. & Tracey, K. J. Mechanisms and therapeutic relevance of neuro-immune communication. Immunity 46, 927–942 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, X. et al. Brain control of humoral immune responses amenable to behavioural modulation. Nature 581, 204–208 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Faust, H. J. et al. IL-17 and immunologically induced senescence regulate response to injury in osteoarthritis. J. Clin. Invest. 130, 5493–5507 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Milligan, E. D. & Watkins, L. R. Pathological and protective roles of glia in chronic pain. Nat. Rev. Neurosci. 10, 23–36 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gangadharan, V. et al. Neuropathic pain caused by miswiring and abnormal end organ targeting. Nature 606, 137–145 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Bethea, J. R. & Fischer, R. Role of peripheral immune cells for development and recovery of chronic pain. Front. Immunol. 12, 641588 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kavelaars, A. & Heijnen, C. J. Immune regulation of pain: friend and foe. Sci. Transl. Med. 13, eabj7152 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Costigan, M. et al. T-cell infiltration and signaling in the adult dorsal spinal cord is a major contributor to neuropathic pain-like hypersensitivity. J. Neurosci. 29, 14415–14422 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Mota, C. M. D. & Madden, C. J. Neural control of the spleen as an effector of immune responses to inflammation: mechanisms and treatments. Am. J. Physiol. Regul. Integr. Comp. Physiol. 323, R375–R384 (2022).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Susaki, E. A. et al. Advanced CUBIC protocols for whole-brain and whole-body clearing and imaging. Nat. Protoc. 10, 1709–1727 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Xiao, X. et al. A genetically defined compartmentalized striatal direct pathway for negative reinforcement. Cell 183, 211–227 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ren, J. et al. Anatomically defined and functionally distinct dorsal raphe serotonin sub-systems. Cell 175, 472–487 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhu, X. et al. Distinct thalamocortical circuits underlie allodynia induced by tissue injury and by depression-like states. Nat. Neurosci. 24, 542–553 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhuo, M. Cortical excitation and chronic pain. Trends Neurosci. 31, 199–207 (2008).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhou, W. et al. A neural circuit for comorbid depressive symptoms in chronic pain. Nat. Neurosci. 22, 1649–1658 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Zhu, X. et al. A central amygdala input to the parafascicular nucleus controls comorbid pain in depression. Cell Rep. 29, 3847–3858.e5 (2019).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Janak, P. H. & Tye, K. M. From circuits to behaviour in the amygdala. Nature 517, 284–292 (2015).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Travagli, R. A., Hermann, G. E., Browning, K. N. & Rogers, R. C. Brainstem circuits regulating gastric function. Annu. Rev. Physiol. 68, 279–305 (2006).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Reilly, F. D., McCuskey, R. S. & Meineke, H. A. Studies of the hemopoietic microenvironment. VIII. Andrenergic and cholinergic innervation of the murine spleen. Anat. Rec. 185, 109–117 (1976).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Nance, D. M. & Burns, J. Innervation of the spleen in the rat: evidence for absence of afferent innervation. Brain Behav. Immun. 3, 281–290 (1989).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Bellinger, D. L., Lorton, D., Hamill, R. W., Felten, S. Y. & Felten, D. L. Acetylcholinesterase staining and choline acetyltransferase activity in the young adult rat spleen: lack of evidence for cholinergic innervation. Brain Behav. Immun. 7, 191–204 (1993).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Cano, G., Sved, A. F., Rinaman, L., Rabin, B. S. & Card, J. P. Characterization of the central nervous system innervation of the rat spleen using viral transneuronal tracing. J. Comp. Neurol. 439, 1–18 (2001).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Gautron, L. et al. Neuronal and nonneuronal cholinergic structures in the mouse gastrointestinal tract and spleen. J. Comp. Neurol. 521, 3741–3767 (2013).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Buijs, R. M., van der Vliet, J., Garidou, M. L., Huitinga, I. & Escobar, C. Spleen vagal denervation inhibits the production of antibodies to circulating antigens. PLoS ONE 3, e3152 (2008).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Kudoh, G., Hoshi, K. & Murakami, T. Fluorescence microscopic and enzyme histochemical studies of the innervation of the human spleen. Arch. Histol. Jpn. 42, 169–180 (1979).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Basbaum, A. I., Bautista, D. M., Scherrer, G. & Julius, D. Cellular and molecular mechanisms of pain. Cell 139, 267–284 (2009).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Koren, T. et al. Insular cortex neurons encode and retrieve specific immune responses.Cell 184, 5902–5915.e17 (2021).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Fan, K. Q. et al. Stress-induced metabolic disorder in peripheral CD4+ T cells leads to anxiety-like behavior. Cell 179, 864–879 (2019).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Qing, H. et al. Origin and function of stress-induced IL-6 in murine models. Cell 182, 372–387 (2020).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Ben-Shaanan, T. L. et al. Modulation of anti-tumor immunity by the brain’s reward system. Nat. Commun. 9, 2723 (2018).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Zhang, Z., Li, Y., Lv, X., Zhao, L. & Wang, X. VLM catecholaminergic neurons control tumor growth by regulating CD8+ T cells. Proc. Natl Acad. Sci. USA 118, e2103505118 (2021).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • McMahon, S. B., La Russa, F. & Bennett, D. L. Crosstalk between the nociceptive and immune systems in host defence and disease. Nat. Rev. Neurosci. 16, 389–402 (2015).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Rosas-Ballina, M. et al. Splenic nerve is required for cholinergic antiinflammatory pathway control of TNF in endotoxemia. Proc. Natl Acad. Sci. USA 105, 11008–11013 (2008).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Filiano, A. J., Gadani, S. P. & Kipnis, J. How and why do T cells and their derived cytokines affect the injured and healthy brain? Nat. Rev. Neurosci. 18, 375–384 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Shin, G. et al. Flexible near-field wireless optoelectronics as subdermal implants for broad applications in optogenetics. Neuron 93, 509–521 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Schindelin, J. et al. Fiji: an open-source platform for biological-image analysis. Nat. Methods 9, 676–682 (2012).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Giovannucci, A. et al. CaImAn an open source tool for scalable calcium imaging data analysis. eLife 8, e38173 (2019).

    Article 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Gong, R., Xu, S., Hermundstad, A., Yu, Y. & Sternson, S. M. Hindbrain double-negative feedback mediates palatability-guided food and water consumption. Cell 182, 1589–1605 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     

  • Liu, Y. et al. Touch and tactile neuropathic pain sensitivity are set by corticospinal projections. Nature 561, 547–550 (2018).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Sheintuch, L. et al. Tracking the same neurons across multiple days in Ca2+ imaging data. Cell Rep. 21, 1102–1115 (2017).

    Article 
    CAS 
    PubMed 
    PubMed Central 

    Google Scholar
     

  • Chen, Y. et al. A versatile tiling light sheet microscope for imaging of cleared tissues. Cell Rep. 33, 108349 (2020).

    Article 
    CAS 
    PubMed 

    Google Scholar
     


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