Activity-dependent central sensitization (CS)

Description

Neuroscience of Pain (Sensitization) Mind Map on Activity-dependent central sensitization (CS), created by Cher Bachar on 16/04/2013.
Cher Bachar
Mind Map by Cher Bachar, updated more than 1 year ago
Cher Bachar
Created by Cher Bachar over 11 years ago
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Resource summary

Activity-dependent central sensitization (CS)
  1. Induction/ maintenance

    Attachments:

    1. Glutamate
      1. NMDR
        1. Induction
          1. antagonists

            Annotations:

            • blocking NMDRs by non-competitive/ competitive anta>> prevents and reverses hyperexcitability of nociceptive neurons
            1. subunit deletion

              Annotations:

              • abolishes NMDA synaptic inputs and acute activity-dependent central sensitization
            2. Maintenance

              Annotations:

              •    o   SP and CGRP>> remove the Mg block by depolarisation o   Glutamate>> generates an inward Ca current  o   >> activates intracellular pathways>> Contributes to maintenance of CS   
            3. mGluRs
              1. Group I

                Annotations:

                • mGluR1 and 5) are coupled with Gαq-proteins (whose activation causes an increase of [Ca2+]
                1. Induction
                2. Group II

                  Annotations:

                  • mGluR 2 and 3
                  1. blocks induction
                  2. Group III

                    Annotations:

                    • mGluR4, 6, 7 and 8) are coupled with Gαi/o-proteins
                    1. Lamina

                      Annotations:

                      • There is a lamina-specific pattern of expression has been characterized for mGluR1α (lamina V), mGluR5 (laminas I-II), mGluR2/3 (lamina II inner),suggesting precise and distinct physiological roles for the different subtypes
                    2. Kainate (KA)
                      1. AMPAR
                      2. NMDR
                        1. Substance P (SP)
                          1. Neurokinin 1 (NK1)
                            1. Induction

                              Annotations:

                              • Ablation of NK1-positive neurons in the spinal cord leads to a reduction in capsaicin-evoked central sensitization   
                          2. CGRP

                            Annotations:

                            • Calcitonin gene-related peptide  Enhances the release of BDNF
                              1. CGRP1 receptor

                                Annotations:

                                • participates in central sensitization through postsynaptic CGRP1 receptors, which activate PKA and PKC
                                1. Annotations:

                                  • potentiates the effects of SP
                                2. BDNF

                                  Annotations:

                                  • brain-derived neurotrophic factor  may contribute to its involvement in migraine and other primary headaches
                                  • release in enhanced by CGRP
                                  1. trkB receptor
                                    1. Annotations:

                                      • BDNF enhances NMDAR-mediated C-fiber–evoked responses and causes activation of several signaling pathways in spinothalamic track neurons, including ERK,and PKC
                                  2. Signalling pathways
                                    1. Induction

                                      Attachments:

                                      1. Role for Ca
                                        1. NMDAR Phosphorylation (P)
                                          1. AMPAR (P)
                                            1. activates PKC/ CAMKII
                                            2. Maintenance

                                              Attachments:

                                              1. multiple pathways

                                                Attachments:

                                              2. NO
                                              3. Synaptic plasticity
                                                1. Homosynaptic
                                                  1. Heterosynaptic
                                                  2. Pathology
                                                    1. Inflammatory
                                                      1. Neuropathic
                                                      2. Phases
                                                        1. Early
                                                          1. Late
                                                          2. Features
                                                            1. Induced by short latency (seconds)
                                                              1. intense, repeated, or sustained nociceptor inputs
                                                                1. Long-lasting
                                                                  1. Multiple pathways for induction

                                                                    Attachments:

                                                                    1. NMDAR
                                                                      1. AMPAR
                                                                        1. Why?
                                                                          1. Interaction needed
                                                                            1. Parallel inputs
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