The cellular mechanism by which the rostral ventromedial medulla acts on the spinal cord during chronic pain

References

Aicher, S.A., Hermes, S.M., Whittier, K.L., and Hegarty, D.M. (2012). Descending projections from the rostral ventromedial medulla (RVM) to trigeminal and spinal dorsal horns are morphologically and neurochemically distinct. J. Chem. Neuroanat. 43: 103–111, https://doi.org/10.1016/j.jchemneu.2011.11.002.Search in Google Scholar

Ambrose, K.R. and Golightly, Y.M. (2015). Physical exercise as non-pharmacological treatment of chronic pain: why and when. Best Pract. Res. Clin. Rheumatol. 29: 120–130, https://doi.org/10.1016/j.berh.2015.04.022.Search in Google Scholar

Baamonde, A., Hidalgo, A., and Menéndez, L.J.N.L. (2011). Involvement of glutamate NMDA and AMPA receptors, glial cells and IL-1β in the spinal hyperalgesia evoked by the chemokine CCL2 in mice. Neurosci. Lett. 502: 178–181, https://doi.org/10.1016/j.neulet.2011.07.038.Search in Google Scholar

Bee, L.A. and Dickenson, A.H. (2008). Descending facilitation from the brainstem determines behavioural and neuronal hypersensitivity following nerve injury and efficacy of pregabalin. Pain 140: 209–223, https://doi.org/10.1016/j.pain.2008.08.008.Search in Google Scholar

Blanco, M.J., La, D., Coughlin, Q., Newman, C.A., Griffin, A.M., Harrison, B.L., and Salituro, F.G. (2018). Breakthroughs in neuroactive steroid drug discovery. Bioorg. Med. Chem. Lett. 28: 61–70, https://doi.org/10.1016/j.bmcl.2017.11.043.Search in Google Scholar

Brito, R.G., Rasmussen, L.A., and Sluka, K.A. (2017). Regular physical activity prevents development of chronic muscle pain through modulation of supraspinal opioid and serotonergic mechanisms. Pain Rep. 2: e618, https://doi.org/10.1097/pr9.0000000000000618.Search in Google Scholar

Budai, D., Khasabov, S.G., Mantyh, P.W., and Simone, D.A. (2007). NK-1 receptors modulate the excitability of ON cells in the rostral ventromedial medulla. J. Neurophysiol. 97: 1388–1395, https://doi.org/10.1152/jn.00450.2006.Search in Google Scholar

Burma, N.E., Leduc-Pessah, H., Fan, C.Y., and Trang, T. (2017). Animal models of chronic pain: advances and challenges for clinical translation. J. Neurosci. Res. 95: 1242–1256, https://doi.org/10.1002/jnr.23768.Search in Google Scholar

Burston, J.J. and Woodhams, S.G. (2014). Endocannabinoid system and pain: an introduction. Proc. Nutr. Soc. 73: 106–117, https://doi.org/10.1017/s0029665113003650.Search in Google Scholar

Cai, Y.Q., Wang, W., Hou, Y.Y., and Pan, Z.Z. (2014). Optogenetic activation of brainstem serotonergic neurons induces persistent pain sensitization. Mol. Pain 10: 70, https://doi.org/10.1186/1744-8069-10-70.Search in Google Scholar

Carlson, J.D., Maire, J.J., Martenson, M.E., and Heinricher, M.M. (2007). Sensitization of pain-modulating neurons in the rostral ventromedial medulla after peripheral nerve injury. J. Neurosci. 27: 13222–13231, https://doi.org/10.1523/jneurosci.3715-07.2007.Search in Google Scholar

Chai, B., Guo, W., Wei, F., Dubner, R., and Ren, K. (2012). Trigeminal-rostral ventromedial medulla circuitry is involved in orofacial hyperalgesia contralateral to tissue injury. Mol. Pain 8: 78, https://doi.org/10.1186/1744-8069-8-78.Search in Google Scholar

Chen, Q., Roeder, Z., Li, M.H., Zhang, Y., Ingram, S.L., and Heinricher, M.M. (2017). Optogenetic evidence for a direct circuit linking nociceptive transmission through the parabrachial complex with pain-modulating neurons of the rostral ventromedial medulla (RVM). eNeuro 4, https://doi.org/10.1523/eneuro.0202-17.2017.Search in Google Scholar

Chen, G., Xie, R.G., Gao, Y.J., Xu, Z.Z., Zhao, L.X., Bang, S., Berta, T., Park, C.K., Lay, M., and Chen, W.J.N.C. (2016). β-Arrestin-2 regulates NMDA receptor function in spinal lamina II neurons and duration of persistent pain. Nat. Commun. 7: 12531, https://doi.org/10.1038/ncomms12531.Search in Google Scholar

Chen, G., Zhang, Y.Q., Qadri, Y.J., Serhan, C.N., and Ji, R.R. (2018). Microglia in pain: detrimental and protective roles in pathogenesis and resolution of pain. Neuron 100: 1292–1311, https://doi.org/10.1016/j.neuron.2018.11.009.Search in Google Scholar

Conte, D., Legg, E.D., McCourt, A.C., Silajdzic, E., Nagy, G.G., and Maxwell, D.J. (2005). Transmitter content, origins and connections of axons in the spinal cord that possess the serotonin (5-hydroxytryptamine) 3 receptor. Neuroscience 134: 165–173, https://doi.org/10.1016/j.neuroscience.2005.02.013.Search in Google Scholar

Corder, G., Castro, D.C., Bruchas, M.R., and Scherrer, G. (2018). Endogenous and exogenous opioids in pain. Annu. Rev. Neurosci. 41: 453–473, https://doi.org/10.1146/annurev-neuro-080317-061522.Search in Google Scholar

Cortes-Altamirano, J.L., Olmos-Hernandez, A., Jaime, H.B., Carrillo-Mora, P., Bandala, C., Reyes-Long, S., and Alfaro-Rodriguez, A. (2018). Review: 5-HT1, 5-HT2, 5-HT3 and 5-HT7 receptors and their role in the modulation of pain response in the central nervous system. Curr. Neuropharmacol. 16: 210–221, https://doi.org/10.2174/1570159x15666170911121027.Search in Google Scholar

Costa-Pereira, J.T., Serrao, P., Martins, I., and Tavares, I. (2020). Serotoninergic pain modulation from the rostral ventromedial medulla (RVM) in chemotherapy-induced neuropathy: the role of spinal 5-HT3 receptors. Eur. J. Neurosci. 51: 1756–1769, https://doi.org/10.1111/ejn.14614.Search in Google Scholar

Crofford, L.J. (2015). Chronic pain: where the body meets the brain. Trans. Am. Clin. Climatol. Assoc. 126: 167–183.Search in Google Scholar

Cruccu, G., Garcia-Larrea, L., Hansson, P., Keindl, M., Lefaucheur, J.P., Paulus, W., Taylor, R., Tronnier, V., Truini, A., and Attal, N. (2016). EAN guidelines on central neurostimulation therapy in chronic pain conditions. Eur. J. Neurol. 23: 1489–1499, https://doi.org/10.1111/ene.13103.Search in Google Scholar

Cull-Candy, S., Brickley, S., and Farrant, M. (2001). NMDA receptor subunits: diversity, development and disease. Curr. Opin. Neurobiol. 11: 327–335, https://doi.org/10.1016/s0959-4388(00)00215-4.Search in Google Scholar

de Novellis, V., Mariani, L., Palazzo, E., Vita, D., Marabese, I., Scafuro, M., Rossi, F., and Maione, S. (2005). Periaqueductal grey CB1 cannabinoid and metabotropic glutamate subtype 5 receptors modulate changes in rostral ventromedial medulla neuronal activities induced by subcutaneous formalin in the rat. Neuroscience 134: 269–281, https://doi.org/10.1016/j.neuroscience.2005.03.014.Search in Google Scholar

Dogrul, A., Ossipov, M.H., and Porreca, F. (2009). Differential mediation of descending pain facilitation and inhibition by spinal 5HT-3 and 5HT-7 receptors. Brain Res. 1280: 52–59, https://doi.org/10.1016/j.brainres.2009.05.001.Search in Google Scholar

Doly, S., Fischer, J., Brisorgueil, M.J., Vergé, D., and Conrath, M. (2005). Pre- and postsynaptic localization of the 5-HT7 receptor in rat dorsal spinal cord: immunocytochemical evidence. J. Comp. Neurol. 490: 256–269, https://doi.org/10.1002/cne.20667.Search in Google Scholar

Drew, G.M., Lau, B.K., and Vaughan, C.W. (2009). Substance P drives endocannabinoid-mediated disinhibition in a midbrain descending analgesic pathway. J. Neurosci. 29: 7220–7229, https://doi.org/10.1523/jneurosci.4362-08.2009.Search in Google Scholar

Enza, P., Livio, L., De, N.V., Francesco, R., and Sabatino, M.J.P. (2010). The role of cannabinoid receptors in the descending modulation of pain. Pharmaceuticals (Basel) 3: 2661–2673.10.3390/ph3082661Search in Google Scholar PubMed PubMed Central

Escobar, W., Ramirez, K., Avila, C., Limongi, R., Vanegas, H., and Vazquez, E. (2012). Metamizol, a non-opioid analgesic, acts via endocannabinoids in the PAG-RVM axis during inflammation in rats. Eur. J. Pain 16: 676–689, https://doi.org/10.1002/j.1532-2149.2011.00057.x.Search in Google Scholar

Fei, Y., Wang, X., Chen, S., Zhou, Q., Zhang, C., Li, Y., Sun, L., and Zhang, L. (2016). Role of the RVM in descending pain regulation originating from the cerebrospinal fluid-contacting nucleus. Neurochem. Res. 41(7): 1651–1661, https://doi.org/10.1007/s11064-016-1880-6.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

Francois, 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, e826, https://doi.org/10.1016/j.neuron.2017.01.008.Search in Google Scholar

Fritzius, T., Stawarski, M., Isogai, S., and Bettler, B. (2020). Structural basis of GABA(B) receptor regulation and signaling. Curr. Top. Behav. Neurosci., https://doi.org/10.1007/7854_2020_147.Search in Google Scholar

Gao, Y.J., Zhang, L., Samad, O.A., Suter, M.R., and Ji, R. (2009). JNK-induced MCP-1 production in spinal cord astrocytes contributes to central sensitization and neuropathic pain. J. Neurosci. 29: 4096–4108, https://doi.org/10.1523/jneurosci.3623-08.2009.Search in Google Scholar

Geneen, L.J., Moore, R.A., Clarke, C., Martin, D., Colvin, L.A., and Smith, B.H. (2017). Physical activity and exercise for chronic pain in adults: an overview of Cochrane Reviews. Cochrane Database Syst. Rev. 4: CD011279, https://doi.org/10.1002/14651858.CD011279.pub3.Search in Google Scholar

Goncalves, L., Almeida, A., and Pertovaara, A. (2007). Pronociceptive changes in response properties of rostroventromedial medullary neurons in a rat model of peripheral neuropathy. Eur. J. Neurosci. 26: 2188–2195, https://doi.org/10.1111/j.1460-9568.2007.05832.x.Search in Google Scholar

Grenald, S.A., Young, M.A., Wang, Y., Ossipov, M.H., Ibrahim, M.M., Largent-Milnes, T.M., and Vanderah, T.W. (2017). Synergistic attenuation of chronic pain using mu opioid and cannabinoid receptor 2 agonists. Neuropharmacology 116: 59–70, https://doi.org/10.1016/j.neuropharm.2016.12.008.Search in Google Scholar

Guan, Y., Guo, W., Robbins, M.T., Dubner, R., and Ren, K. (2004). Changes in AMPA receptor phosphorylation in the rostral ventromedial medulla after inflammatory hyperalgesia in rats. Neurosci. Lett. 366: 201–205, https://doi.org/10.1016/j.neulet.2004.05.051.Search in Google Scholar

Guo, W., Miyoshi, K., Dubner, R., Gu, M., Li, M., Liu, J., Yang, J., Zou, S., Ren, K., Noguchi, K., et al.. (2014). Spinal 5-HT3 receptors mediate descending facilitation and contribute to behavioral hypersensitivity via a reciprocal neuron-glial signaling cascade. Mol. Pain 10: 35, https://doi.org/10.1186/1744-8069-10-35.Search in Google Scholar

Guo, W., Robbins, M.T., Wei, F., Zou, S., Dubner, R., and Ren, K. (2006). Supraspinal brain-derived neurotrophic factor signaling: a novel mechanism for descending pain facilitation. J. Neurosci. 26: 126–137, https://doi.org/10.1523/jneurosci.3686-05.2006.Search in Google Scholar

Guo, W., Wang, H., Watanabe, M., Shimizu, K., Zou, S., LaGraize, S.C., Wei, F., Dubner, R., and Ren, K. (2007). Glial-cytokine-neuronal interactions underlying the mechanisms of persistent pain. J. Neurosci. 27: 6006–6018, https://doi.org/10.1523/jneurosci.0176-07.2007.Search in Google Scholar

Guo, W., Wang, H., Zou, S., Dubner, R., and Ren, K. (2012). Chemokine signaling involving chemokine (C-C motif) ligand 2 plays a role in descending pain facilitation. Neurosci. Bull. 28: 193–207, https://doi.org/10.1007/s12264-012-1218-6.Search in Google Scholar

Hamity, M.V., White, S.R., and Hammond, D.L. (2010). Effects of neurokinin-1 receptor agonism and antagonism in the rostral ventromedial medulla of rats with acute or persistent inflammatory nociception. Neuroscience 165: 902–913, https://doi.org/10.1016/j.neuroscience.2009.10.064.Search in Google Scholar

Harasawa, I., Johansen, J.P., Fields, H.L., Porreca, F., and Meng, I.D. (2016). Alterations in the rostral ventromedial medulla after the selective ablation of μ-opioid receptor expressing neurons. Pain 157: 166–173, https://doi.org/10.1097/j.pain.0000000000000344.Search in Google Scholar

Heinricher, M.M., Mcgaraughty, S., and Tortorici, V.J. (2001a). Circuitry underlying antiopioid actions of cholecystokinin within the rostral ventromedial medulla. J. Neurophysiol. 85: 280–286, https://doi.org/10.1152/jn.2001.85.1.280.Search in Google Scholar

Heinricher, M.M. and Neubert, M.J. (2004). Neural basis for the hyperalgesic action of cholecystokinin in the rostral ventromedial medulla. J. Neurophysiol. 92: 1982, https://doi.org/10.1152/jn.00411.2004.Search in Google Scholar

Heinricher, M.M., Schouten, J.C., and Jobst, E.E. (2001b). Activation of brainstem N-methyl-D-aspartate receptors is required for the analgesic actions of morphine given systemically. Pain 92: 129–138, https://doi.org/10.1016/s0304-3959(00)00480-2.Search in Google Scholar

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

Helander, E.M., Menard, B.L., Harmon, C.M., Homra, B.K., Allain, A.V., Bordelon, G.J., Wyche, M.Q., Padnos, I.W., Lavrova, A., and Kaye, A.D. (2017). Multimodal analgesia, current concepts, and acute pain considerations. Curr. Pain Headache Rep. 21: 3, https://doi.org/10.1007/s11916-017-0607-y.Search in Google Scholar

Hosseini, M., Parviz, M., Shabanzadeh, A.P., Zamani, E., Mohseni-Moghaddam, P., Gholami, L., and Mehrabadi, S. (2020). The inhibiting role of periaqueductal gray metabotropic glutamate receptor subtype 8 in a rat model of central neuropathic pain. Neurol. Res. 42: 515–521, https://doi.org/10.1080/01616412.2020.1747730.Search in Google Scholar

Huang, Z.X., Lu, Z.J., Ma, W.Q., Wu, F.X., Zhang, Y.Q., Yu, W.F., and Zhao, Z.Q.J.P. (2014). Involvement of RVM-expressed P2X7 receptor in bone cancer pain: mechanism of descending facilitation. Pain 155: 783–791, https://doi.org/10.1016/j.pain.2014.01.011.Search in Google Scholar

Imbe, H. and Kimura, A. (2018). Increase of histone acetylation in the GABAergic neurons in the rostral ventromedial medulla associated with mechanical hypersensitivity after repeated restraint stress. Brain Res. Bull. 142: 394–402, https://doi.org/10.1016/j.brainresbull.2018.09.004.Search in Google Scholar

Imbe, H., Okamoto, K., Okamura, T., Kumabe, S., Nakatsuka, M., Aikawa, F., Iwai-Liao, Y., and Senba, E. (2005). Effects of peripheral inflammation on activation of ERK in the rostral ventromedial medulla. Brain Res. 1063: 151–158, https://doi.org/10.1016/j.brainres.2005.09.057.Search in Google Scholar

Jens, E., Coskun, U., and Schnell, C. (2000). Are ’neutral cells’ in the rostral ventro-medial medulla subtypes of on- and off-cells?. Neurosci. Res. 38: 419–423.10.1016/S0168-0102(00)00190-5Search in Google Scholar

Ji, R.R., Chamessian, A., and Zhang, Y.Q. (2016). Pain regulation by non-neuronal cells and inflammation. Science 354: 572–577, https://doi.org/10.1126/science.aaf8924.Search in Google Scholar

Jiang, M., Bo, J., Lei, Y., Hu, F., Xia, Z., Liu, Y., Lu, C., Sun, Y., Hou, B., Ni, K., et al.. (2019). Anxiety-induced hyperalgesia in female rats is mediated by cholecystokinin 2 receptor in rostral ventromedial medulla and spinal 5-hydroxytryptamine 2B receptor. J. Pain Res. 12: 2009–2026, https://doi.org/10.2147/jpr.s187715.Search in Google Scholar

Jung, M.J., Lippert, B., Metcalf, B.W., Böhlen, P., and Schechter, P. (2010). gamma-Vinyl GABA (4-amino-hex-5-enoic acid), a new selective irreversible inhibitor of GABA-T: effects on brain GABA metabolism in mice. J. Neurochem. 29: 797–802.10.1111/j.1471-4159.1977.tb10721.xSearch in Google Scholar

Keppel Hesselink, J.M. (2020). Rediscovery of ceruletide, a CCK agonist, as an analgesic drug. J. Pain Res. 13: 123–130, https://doi.org/10.2147/jpr.s232714.Search in Google Scholar

Kim, Y.-J., Byun, J.-H., and Choi, I.-S. (2015). Effect of exercise on µ-opioid receptor expression in the rostral ventromedial medulla in neuropathic pain rat model. Ann. Rehabil. Med. 39(3): 331–339, https://doi.org/10.5535/arm.2015.39.3.331.Search in Google Scholar

Kincaid, W., Neubert, M.J., Xu, M., Kim, C.J., and Heinricher, M.M. (2006). Role for medullary pain facilitating neurons in secondary thermal hyperalgesia. J. Neurophysiol. 95: 33–41, https://doi.org/10.1152/jn.00449.2005.Search in Google Scholar

Kovelowski, C.J., Ossipov, M.H., Sun, H., Lai, J., and Porreca, F.J.P. (2000). Supraspinal cholecystokinin may drive tonic descending facilitation mechanisms to maintain neuropathic pain in the rat. Pain 87: 265–273, https://doi.org/10.1016/s0304-3959(00)00290-6.Search in Google Scholar

Kuner, R. (2010). Central mechanisms of pathological pain. Nat. Med. 16: 1258–1266, https://doi.org/10.1038/nm.2231.Search in Google Scholar

LaGraize, S.C., Guo, W., Yang, K., and Neuroscience, F.J. (2010). Spinal cord mechanisms mediating behavioral hyperalgesia induced by neurokinin-1 tachykinin receptor activation in the rostral ventromedial medulla. Neuroscience 171: 1341–1356, https://doi.org/10.1016/j.neuroscience.2010.09.040.Search in Google Scholar

Lau, B.K., Winters, B.L., and Vaughan, C.W. (2020). Opioid presynaptic disinhibition of the midbrain periaqueductal grey descending analgesic pathway. Br. J. Pharmacol. 177: 2320–2332, https://doi.org/10.1111/bph.14982.Search in Google Scholar

Lee, M., Silverman, S.M., Hansen, H., Patel, V.B., and Manchikanti, L. (2011). A comprehensive review of opioid-induced hyperalgesia. Pain Physician 14: 145–161.10.36076/ppj.2011/14/145Search in Google Scholar

Leong, M.L., Gu, M., Speltz-Paiz, R., Stahura, E.I., Mottey, N., Steer, C.J., and Wessendorf, M. (2011). Neuronal loss in the rostral ventromedial medulla in a rat model of neuropathic pain. J. Neurosci. 31: 17028–17039, https://doi.org/10.1523/jneurosci.1268-11.2011.Search in Google Scholar

Leong, M.L., Speltz, R., and Wessendorf, M. (2016). Effects of chronic constriction injury and spared nerve injury, two models of neuropathic pain, on the numbers of neurons and glia in the rostral ventromedial medulla. Neurosci. Lett. 617: 82–87, https://doi.org/10.1016/j.neulet.2016.02.006.Search in Google Scholar

Li, M.H., Suchland, K.L., and Ingram, S.L. (2015). GABAergic transmission and enhanced modulation by opioids and endocannabinoids in adult rat rostral ventromedial medulla. J. Physiol. 593: 217–230, https://doi.org/10.1113/jphysiol.2014.275701.Search in Google Scholar

Li, M.H., Suchland, K.L., and Ingram, S.L. (2017). Compensatory activation of cannabinoid CB2 receptor inhibition of GABA release in the rostral ventromedial medulla in inflammatory pain. J. Neurosci. 37: 626–636, https://doi.org/10.1523/jneurosci.1310-16.2017.Search in Google Scholar

Lisman, J. (2017). Glutamatergic synapses are structurally and biochemically complex because of multiple plasticity processes: long-term potentiation, long-term depression, short-term potentiation and scaling. Philos. Trans. R. Soc. Lond. B Biol. Sci. 372, https://doi.org/10.1098/rstb.2016.0260.Search in Google Scholar

Liu, X., Wang, G., Ai, G., Xu, X., Niu, X., and Zhang, M. (2020). Selective ablation of descending serotonin from the rostral ventromedial medulla unmasks its pro-nociceptive role in chemotherapy-induced painful neuropathy. J. Pain Res. 13: 3081–3094, https://doi.org/10.2147/jpr.s275254.Search in Google Scholar

Liu, P., Yuan, H.B., Zhao, S., Liu, F.F., Jiang, Y.Q., Guo, Y.X., and Wang, X.L. (2018). Activation of GABAB receptor suppresses diabetic neuropathic pain through toll-like receptor 4 signaling pathway in the spinal dorsal horn. Mediat. Inflamm. 2018: 6016272, https://doi.org/10.1155/2018/6016272.Search in Google Scholar

Liu, F., Zhang, Y.Y., Song, N., Lin, J., Liu, M.K., Huang, C.L., Zhou, C., Wang, H., Wang, M., and Shen, J.F. (2019). GABAB receptor activation attenuates inflammatory orofacial pain by modulating interleukin-1beta in satellite glial cells: role of NF-kappaB and MAPK signaling pathways. Brain Res. Bull. 149: 240–250, https://doi.org/10.1016/j.brainresbull.2019.04.018.Search in Google Scholar

Lueptow, L.M., Fakira, A.K., and Bobeck, E.N. (2018). The contribution of the descending pain modulatory pathway in opioid tolerance. Front. Neurosci. 12: 886, https://doi.org/10.3389/fnins.2018.00886.Search in Google Scholar

Malcangio, M. (2018). GABAB receptors and pain. Neuropharmacology 136: 102–105, https://doi.org/10.1016/j.neuropharm.2017.05.012.Search in Google Scholar

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

Marshall, T.M., Herman, D.S., Largent-Milnes, T.M., Badghisi, H., Zuber, K., Holt, S.C., Lai, J., Porreca, F., and Vanderah, T.W. (2012). Activation of descending pain-facilitatory pathways from the rostral ventromedial medulla by cholecystokinin elicits release of prostaglandin-E₂ in the spinal cord. Pain 153(1): 86–94, https://doi.org/10.1016/j.pain.2011.09.021.Search in Google Scholar

Martins, I. and Tavares, I. (2017). Reticular formation and pain: the past and the future. Front. Neuroanat. 11: 51, https://doi.org/10.3389/fnana.2017.00051.Search in Google Scholar

Medeiros, P., Negrini-Ferrari, S.E., Palazzo, E., Maione, S., Ferreira, S.H., de Freitas, R.L., and Coimbra, N.C. (2019). N-methyl-D-aspartate receptors in the prelimbic cortex are critical for the maintenance of neuropathic pain. Neurochem. Res. 44: 2068–2080, https://doi.org/10.1007/s11064-019-02843-z.Search in Google Scholar

Meng, I.D. and Harasawa, I. (2007). Chronic morphine exposure increases the proportion of on-cells in the rostral ventromedial medulla in rats. Life Sci. 80: 1915–1920, https://doi.org/10.1016/j.lfs.2007.02.022.Search in Google Scholar

Meng, I.D. and Johansen, J.P. (2004). Antinociception and modulation of rostral ventromedial medulla neuronal activity by local microinfusion of a cannabinoid receptor agonist. Neuroscience 124: 685–693, https://doi.org/10.1016/j.neuroscience.2003.10.001.Search in Google Scholar

Mills, E.P., Di Pietro, F., Alshelh, Z., Peck, C.C., Murray, G.M., Vickers, E.R., and Henderson, L.A. (2018). Brainstem pain-control circuitry connectivity in chronic neuropathic pain. J. Neurosci. 38: 465–473, https://doi.org/10.1523/jneurosci.1647-17.2017.Search in Google Scholar

Moisset, X., Lanteri-Minet, M., and Fontaine, D. (2020). Neurostimulation methods in the treatment of chronic pain. J. Neural. Transm. 127: 673–686, https://doi.org/10.1007/s00702-019-02092-y.Search in Google Scholar

Morgan, M.M., Whittier, K.L., Hegarty, D.M., and Aicher, S.A. (2008). Periaqueductal gray neurons project to spinally projecting GABAergic neurons in the rostral ventromedial medulla. Pain 140: 376–386, https://doi.org/10.1016/j.pain.2008.09.009.Search in Google Scholar

Ogawa, S., Natsume, T., and Takamatsu, H. (2018). [Pharmacological profile of a novel nonhuman primate model of knee osteoarthritis]. Nihon Yakurigaku Zasshi 152: 132–138, https://doi.org/10.1254/fpj.152.132.Search in Google Scholar

Old, E.A., Clark, A.K., and Malcangio, M.J.H.E.P. (2015). The role of glia in the spinal cord in neuropathic and inflammatory pain. Handb. Exp. Pharmacol. 227: 145–170, https://doi.org/10.1007/978-3-662-46450-2_8.Search in Google Scholar

Ossipov, M.H., Lai, J., King, T., Vanderah, T.W., and Porreca, F. (2004). Antinociceptive and nociceptive actions of opioids. J. Neurobiol. 61: 126–148, https://doi.org/10.1002/neu.20091.Search in Google Scholar

Ossipov, M.H., Lai, J., Malan, T.P., and Porreca, F. (2010). Spinal and supraspinal mechanisms of neuropathic pain. Ann. N. Y. Acad. Sci. 909: 12–24.10.1111/j.1749-6632.2000.tb06673.xSearch in Google Scholar

Ossipov, M.H., Lai, J., Vanderah, T.W., and Porreca, F. (2003). Induction of pain facilitation by sustained opioid exposure: relationship to opioid antinociceptive tolerance. Life Sci. 73: 783–800, https://doi.org/10.1016/s0024-3205(03)00410-7.Search in Google Scholar

Palazzo, E., Marabese, I., de Novellis, V., Rossi, F., and Maione, S. (2014). Supraspinal metabotropic glutamate receptors: a target for pain relief and beyond. Eur. J. Neurosci. 39: 444–454, https://doi.org/10.1111/ejn.12398.Search in Google Scholar

Paoletti, P., Bellone, C., and Zhou, Q. (2013). NMDA receptor subunit diversity: impact on receptor properties, synaptic plasticity and disease. Nat. Rev. Neurosci. 14: 383–400, https://doi.org/10.1038/nrn3504.Search in Google Scholar

Pedersen, N.P., Vaughan, C.W., and Christie, M.J. (2011). Opioid receptor modulation of GABAergic and serotonergic spinally projecting neurons of the rostral ventromedial medulla in mice. J. Neurophysiol. 106: 731–740, https://doi.org/10.1152/jn.01062.2010.Search in Google Scholar

Pinto, M., Sousa, M., Lima, D., and Tavares, I. (2008). Participation of mu-opioid, GABA(B), and NK1 receptors of major pain control medullary areas in pathways targeting the rat spinal cord: implications for descending modulation of nociceptive transmission. J. Comp. Neurol. 510: 175–187, https://doi.org/10.1002/cne.21793.Search in Google Scholar

Porreca, F., Burgess, S.E., Gardell, L.R., Vanderah, T.W., Malan, T.P.Jr., Ossipov, M.H., Lappi, D.A., and Lai, J. (2001). Inhibition of neuropathic pain by selective ablation of brainstem medullary cells expressing the mu-opioid receptor. J. Neurosci. 21: 5281–5288, https://doi.org/10.1523/jneurosci.21-14-05281.2001.Search in Google Scholar

Roca-Lapirot, O., Fossat, P., Ma, S., Egron, K., Trigilio, G., López-González, M.-J., Covita, J., Bouali-Benazzouz, R., Favereaux, A., and Gundlach, A.L.J.P. (2019). Acquisition of analgesic properties by the cholecystokinin (CCK)/CCK2 receptor system within the amygdala in a persistent inflammatory pain condition. Pain 160: 345–357, https://doi.org/10.1097/j.pain.0000000000001408.Search in Google Scholar

Rossi, F., Marabese, I., De Chiaro, M., Boccella, S., Luongo, L., Guida, F., De Gregorio, D., Giordano, C., de Novellis, V., Palazzo, E., and Maione, S. (2014). Dorsal striatum metabotropic glutamate receptor 8 affects nocifensive responses and rostral ventromedial medulla cell activity in neuropathic pain conditions. J. Neurophysiol. 111(11): 2196–2209, https://doi.org/10.1152/jn.00212.2013.Search in Google Scholar

Sagalajev, B., Viisanen, H., Wei, H., and Pertovaara, A. (2017). Descending antinociception induced by secondary somatosensory cortex stimulation in experimental neuropathy: role of the medullospinal serotonergic pathway. J. Neurophysiol. 117(3): 1200–1214, https://doi.org/10.1152/jn.00836.2016.Search in Google Scholar

Salas, R., Ramirez, K., Tortorici, V., Vanegas, H., and Vazquez, E. (2018). Functional relationship between brainstem putative pain-facilitating neurons and spinal nociceptfive neurons during development of inflammation in rats. Brain Res. 1686: 55–64, https://doi.org/10.1016/j.brainres.2018.02.025.Search in Google Scholar

Salas, R., Ramirez, K., Vanegas, H., and Vazquez, E. (2016). Activity correlations between on-like and off-like cells of the rostral ventromedial medulla and simultaneously recorded wide-dynamic-range neurons of the spinal dorsal horn in rats. Brain Res. 1652: 103–110, https://doi.org/10.1016/j.brainres.2016.10.001.Search in Google Scholar

Samarajeewa, A., Goldemann, L., Vasefi, M.S., Ahmed, N., Gondora, N., Khanderia, C., Mielke, J.G., and Beazely, M.A. (2014). 5-HT7 receptor activation promotes an increase in TrkB receptor expression and phosphorylation. Front. Behav. Neurosci. 8: 391, https://doi.org/10.3389/fnbeh.2014.00391.Search in Google Scholar

Sanoja, R., Vanegas, H., and Tortorici, V. (2008). Critical role of the rostral ventromedial medulla in early spinal events leading to chronic constriction injury neuropathy in rats. J. Pain 9: 532–542, https://doi.org/10.1016/j.jpain.2008.01.332.Search in Google Scholar

Schousboe, A. and Redburn, D.A. (1995). Modulatory actions of gamma aminobutyric acid (GABA) on GABA type a receptor subunit expression and function. J. Neurosci. Res. 41: 1–7, https://doi.org/10.1002/jnr.490410102.Search in Google Scholar

Senba, E., Imbe, H., and Okamoto, K. (2008). [Descending facilitation in chronic stress and chronic pain state]. Nihon Shinkei Seishin Yakurigaku Zasshi 28: 29–35.Search in Google Scholar

Seyrek, M., Kahraman, S., Deveci, M.S., Yesilyurt, O., and Dogrul, A. (2010). Systemic cannabinoids produce CB₁-mediated antinociception by activation of descending serotonergic pathways that act upon spinal 5-HT(7) and 5-HT(2A) receptors. Eur. J. Pharmacol. 649: 183–194, https://doi.org/10.1016/j.ejphar.2010.09.039.Search in Google Scholar

Sheng, J., Liu, S., Wang, Y., Cui, R., and Zhang, X. (2017). The link between depression and chronic pain: neural mechanisms in the brain. Neural Plast 2017: 9724371, https://doi.org/10.1155/2017/9724371.Search in Google Scholar

Shimizu, S., Nakatani, Y., Kakihara, Y., Taiyoji, M., Saeki, M., Takagi, R., Yamamura, K., and Okamoto, K. (2020). Daily administration of Sake Lees (Sake Kasu) reduced psychophysical stress-induced hyperalgesia and Fos responses in the lumbar spinal dorsal horn evoked by noxious stimulation to the hindpaw in the rats. Biosci. Biotechnol. Biochem. 84: 159–170, https://doi.org/10.1080/09168451.2019.1662278.Search in Google Scholar

Sikandar, S., Bannister, K., and Dickenson, A.H. (2012). Brainstem facilitations and descending serotonergic controls contribute to visceral nociception but not pregabalin analgesia in rats. Neurosci. Lett. 519: 31–36, https://doi.org/10.1016/j.neulet.2012.05.009.Search in Google Scholar

Sills, G.J. and Rogawski, M.A. (2020). Mechanisms of action of currently used antiseizure drugs. Neuropharmacology 168: 107966, https://doi.org/10.1016/j.neuropharm.2020.107966.Search in Google Scholar

Silva, M., Costa-Pereira, J.T., Martins, D., and Tavares, I. (2016). Pain modulation from the brain during diabetic neuropathy: uncovering the role of the rostroventromedial medulla. Neurobiol. Dis. 96: 346–356, https://doi.org/10.1016/j.nbd.2016.10.002.Search in Google Scholar

Song, Z., Ansah, O.B., Meyerson, B.A., Pertovaara, A., and Linderoth, B. (2013). The rostroventromedial medulla is engaged in the effects of spinal cord stimulation in a rodent model of neuropathic pain. Neuroscience 247: 134–144, https://doi.org/10.1016/j.neuroscience.2013.05.027.Search in Google Scholar

Song, T., Ma, X., Ma, P., Gu, K., Zhao, J., Yang, Y., Jiang, B., Li, Y., and Wang, C. (2018). Administrations of thalidomide into the rostral ventromedial medulla produce antinociceptive effects in a rat model of postoperative pain. J. Neurosci. Res. 96: 273–283, https://doi.org/10.1002/jnr.24124.Search in Google Scholar

Steinhoff, M.S., von Mentzer, B., Geppetti, P., Pothoulakis, C., and Bunnett, N.W. (2014). Tachykinins and their receptors: contributions to physiological control and the mechanisms of disease. Physiol. Rev. 94: 265–301, https://doi.org/10.1152/physrev.00031.2013.Search in Google Scholar

Suzuki, R., Rahman, W., Hunt, S.P., and Dickenson, A.H. (2004). Descending facilitatory control of mechanically evoked responses is enhanced in deep dorsal horn neurones following peripheral nerve injury. Brain Res. 1019: 68–76, https://doi.org/10.1016/j.brainres.2004.05.108.Search in Google Scholar

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

Tryon, V.L., Mizumori, S.J., and Morgan, M.M. (2016). Analysis of morphine-induced changes in the activity of periaqueductal gray neurons in the intact rat. Neuroscience 335: 1–8, https://doi.org/10.1016/j.neuroscience.2016.08.025.Search in Google Scholar

Viisanen, H., Lilius, T.O., Sagalajev, B., Rauhala, P., Kalso, E., and Pertovaara, A. (2020). Neurophysiological response properties of medullary pain-control neurons following chronic treatment with morphine or oxycodone: modulation by acute ketamine. J. Neurophysiol. 124: 790–801, https://doi.org/10.1152/jn.00343.2020.Search in Google Scholar

Wagner, K., Roeder, Z., Desrochers, K., Buhler, A.V., Heinricher, M.M., and Cleary, D.R.J.o. (2013). The dorsomedial hypothalamus mediates stress-induced hyperalgesia and is the source of the pronociceptive peptide cholecystokinin in the rostral ventromedial medulla. Neuroscience 238: 29–38, https://doi.org/10.1016/j.neuroscience.2013.02.009.Search in Google Scholar

Walters, E.T. (2018). How is chronic pain related to sympathetic dysfunction and autonomic dysreflexia following spinal cord injury?. Auton. Neurosci. 209: 79–89, https://doi.org/10.1016/j.autneu.2017.01.006.Search in Google Scholar

Wang, J., Feng, D.-Y., Li, Z.-H., Feng, B., Zhang, H., Zhang, T., Chen, T., and Li, Y.-Q. (2015). Activation of the mammalian target of rapamycin in the rostral ventromedial medulla contributes to the maintenance of nerve injury-induced neuropathic pain in rat. Neural Plast. 2015: 394820, https://doi.org/10.1155/2015/394820.Search in Google Scholar

Wang, C.-T., Mao, C.-J., Zhang, X.-Q., Zhang, C.-Y., Lv, D.-J., Yang, Y.-P., Xia, K.-L., Liu, J.-Y., Wang, F., Hu, L.-F., et al.. (2017). Attenuation of hyperalgesia responses via the modulation of 5-hydroxytryptamine signalings in the rostral ventromedial medulla and spinal cord in a 6-hydroxydopamine-induced rat model of Parkinson’s disease. Mol. Pain 13, https://doi.org/10.1177/1744806917691525.Search in Google Scholar

Wang, W., Zhong, X., Li, Y., Guo, R., Du, S., Wen, L., Ying, Y., Yang, T., and Wei, X.-H. (2019). Rostral ventromedial medulla-mediated descending facilitation following P2X7 receptor activation is involved in the development of chronic post-operative pain. J. Neurochem. 149(6): 760–780, https://doi.org/10.1111/jnc.14650.Search in Google Scholar

Wei, F., Guo, W., Zou, S., Ren, K., and Dubner, R. (2008). Supraspinal glial-neuronal interactions contribute to descending pain facilitation. J. Neurosci. 28: 10482–10495, https://doi.org/10.1523/jneurosci.3593-08.2008.Search in Google Scholar

Wilson-Poe, A.R., Pocius, E., Herschbach, M., and Morgan, M.M. (2013). The periaqueductal gray contributes to bidirectional enhancement of antinociception between morphine and cannabinoids. Pharmacol. Biochem. Behav. 103: 444–449, https://doi.org/10.1016/j.pbb.2012.10.002.Search in Google Scholar

Yang, K., Ma, W.L., Feng, Y.P., Dong, Y.X., and Li, Y.Q. (2002). Origins of GABA(B) receptor-like immunoreactive terminals in the rat spinal dorsal horn. Brain Res. Bull. 58: 499–507, https://doi.org/10.1016/s0361-9230(02)00824-9.Search in Google Scholar

Yasuda, S., Yoshida, M., Yamagata, H., Iwanaga, Y., Suenaga, H., Ishikawa, K., Nakano, M., Okuyama, S., Furukawa, Y., Furukawa, S., and Ishikawa, T. (2014). Imipramine ameliorates pain-related negative emotion via induction of brain-derived neurotrophic factor. Cell Mol. Neurobiol. 34(8): 1199–1208, https://doi.org/10.1007/s10571-014-0097-y.Search in Google Scholar

Yesilyurt, O., Seyrek, M., Tasdemir, S., Kahraman, S., Deveci, M.S., Karakus, E., Halici, Z., and Dogrul, A. (2015). The critical role of spinal 5-HT7 receptors in opioid and non-opioid type stress-induced analgesia. Eur. J. Pharmacol. 762: 402–410, https://doi.org/10.1016/j.ejphar.2015.04.020.Search in Google Scholar

Yin, J.B., Wu, H.H., Dong, Y.L., Zhang, T., Wang, J., Zhang, Y., Wei, Y.Y., Lu, Y.C., Wu, S.X., Wang, W., et al.. (2014). Neurochemical properties of BDNF-containing neurons projecting to rostral ventromedial medulla in the ventrolateral periaqueductal gray. Front. Neural. Circuits 8: 137, https://doi.org/10.3389/fncir.2014.00137.Search in Google Scholar

Zapata, A., Pontis, S., Schepers, R.J., Wang, R., Oh, E., Stein, A., Backman, C.M., Worley, P., Enguita, M., Abad, M.A., et al.. (2012). Alleviation of neuropathic pain hypersensitivity by inhibiting neuronal pentraxin 1 in the rostral ventromedial medulla. J. Neurosci. 32: 12431–12436, https://doi.org/10.1523/jneurosci.2730-12.2012.Search in Google Scholar

Zeilhofer, H.U., Wildner, H., and Yevenes, G.E. (2012). Fast synaptic inhibition in spinal sensory processing and pain control. Physiol. Rev. 92: 193–235, https://doi.org/10.1152/physrev.00043.2010.Search in Google Scholar

Zhang, Q., Wang, J., Duan, M.T., Han, S.P., Zeng, X.Y., and Wang, J.Y. (2013). NF-kappaB, ERK, p38 MAPK and JNK contribute to the initiation and/or maintenance of mechanical allodynia induced by tumor necrosis factor-alpha in the red nucleus. Brain Res. Bull. 99: 132–139, https://doi.org/10.1016/j.brainresbull.2013.10.008.Search in Google Scholar

Zhang, C., Xia, C., Zhang, X., Li, W., Miao, X., and Zhou, Q. (2020). Wrist-ankle acupuncture attenuates cancer-induced bone pain by regulating descending pain-modulating system in a rat model. Chin. Med. 15: 13, https://doi.org/10.4103/1673-5374.272620.Search in Google Scholar

Zhang, Y., Zhao, S., Rodriguez, E., Takatoh, J., Han, B.X., Zhou, X., and Wang, F. (2015). Identifying local and descending inputs for primary sensory neurons. J. Clin. Invest. 125: 3782–3794, https://doi.org/10.1172/jci81156.Search in Google Scholar

Zhu, J.J., Qin, Y., Zhao, M., Aelst, L.V., and Malinow, R.J.C. (2002). Ras and Rap control AMPA receptor trafficking during synaptic plasticity. Cell 110: 443–455, https://doi.org/10.1016/s0092-8674(02)00897-8.Search in Google Scholar

Zhuo, M. (2017). Ionotropic glutamate receptors contribute to pain transmission and chronic pain. Neuropharmacology 112: 228–234, https://doi.org/10.1016/j.neuropharm.2016.08.014.Search in Google Scholar