Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies
The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modul...
| Principais autores: | , , , , , , , |
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| Formato: | Journal article |
| Idioma: | English |
| Publicado em: |
BMJ
2018
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| _version_ | 1826298450762792960 |
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| author | Xu, M Bennett, D Querol, L Wu, L Irani, S Watson, J Pittock, S Klein, C |
| author_facet | Xu, M Bennett, D Querol, L Wu, L Irani, S Watson, J Pittock, S Klein, C |
| author_sort | Xu, M |
| collection | OXFORD |
| description | The immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways. Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness. Other pain disorders, like complex regional pain disorder, have been associated with IgGs against β2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response. Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches. Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed. |
| first_indexed | 2024-03-07T04:47:02Z |
| format | Journal article |
| id | oxford-uuid:d3a27a39-91d7-4aae-ae4a-af5b4b1f7e6f |
| institution | University of Oxford |
| language | English |
| last_indexed | 2024-03-07T04:47:02Z |
| publishDate | 2018 |
| publisher | BMJ |
| record_format | dspace |
| spelling | oxford-uuid:d3a27a39-91d7-4aae-ae4a-af5b4b1f7e6f2022-03-27T08:12:50ZPain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapiesJournal articlehttp://purl.org/coar/resource_type/c_dcae04bcuuid:d3a27a39-91d7-4aae-ae4a-af5b4b1f7e6fEnglishSymplectic Elements at OxfordBMJ2018Xu, MBennett, DQuerol, LWu, LIrani, SWatson, JPittock, SKlein, CThe immune system has long been recognised important in pain regulation through inflammatory cytokine modulation of peripheral nociceptive fibres. Recently, cytokine interactions in brain and spinal cord glia as well as dorsal root ganglia satellite glia have been identified important- in pain modulation. The result of these interactions is central and peripheral sensitisation of nociceptive processing. Additionally, new insights and the term 'autoimmune pain' have emerged through discovery of specific IgGs targeting the extracellular domains of antigens at nodal and synaptic structures, causing pain directly without inflammation by enhancing neuronal excitability. Other discovered IgGs heighten pain indirectly by T-cell-mediated inflammation or destruction of targets within the nociceptive pathways. Notable identified IgGs in pain include those against the components of channels and receptors involved in inhibitory or excitatory somatosensory synapses or their pathways: nodal and paranodal proteins (LGI1, CASPR1, CASPR2); glutamate detection (AMPA-R); GABA regulation and release (GAD65, amphiphysin); glycine receptors (GLY-R); water channels (AQP4). These disorders have other neurological manifestations of central/peripheral hyperexcitabability including seizures, encephalopathy, myoclonus, tremor and spasticity, with immunotherapy responsiveness. Other pain disorders, like complex regional pain disorder, have been associated with IgGs against β2-adrenergic receptor, muscarinic-2 receptors, AChR-nicotinic ganglionic α-3 receptors and calcium channels (N and P/Q types), but less consistently with immune treatment response. Here, we outline how the immune system contributes to development and regulation of pain, review specific IgG-mediated pain disorders and summarise recent development in therapy approaches. Biological agents to treat pain (anti-calcitonin gene-related peptide and anti-nerve growth factor) are also discussed. |
| spellingShingle | Xu, M Bennett, D Querol, L Wu, L Irani, S Watson, J Pittock, S Klein, C Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies |
| title | Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies |
| title_full | Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies |
| title_fullStr | Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies |
| title_full_unstemmed | Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies |
| title_short | Pain and the immune system: Emerging concepts of IgG-mediated autoimmune pain and immunotherapies |
| title_sort | pain and the immune system emerging concepts of igg mediated autoimmune pain and immunotherapies |
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