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27 Cards in this Set
- Front
- Back
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What are the 4 main mechanisms of spinal sensitization to pain? |
1. Windup 2. Phosphorylation 3. Microglia 4. Axon sprouting |
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What causes windup? |
1. Increased secondary nociceptor activation induced by repeated or continuous primary nociceptor activity |
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What is the development of windup? |
1. Relative rapid (days) |
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What receptors are involved in windup? |
1. NMDA 2. Allow Ca to enter secondary nociceptors |
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How are TRP channels involved in windup? |
1. Activated by Ca to further enhance secondary nociceptor depolarization 2. Leads to higher frequency APs=more intense perceived pain |
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What is the consequence of long-term primary nociceptor activity? |
1. High Ca levels in secondary nociceptors 2. Kinase activation--- long-term potentiation of nociceptive synapses
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What kinases are activated in long-term potentiation? What is their subsequent action? |
1. PKC 2. Ca-calmodulin kinase II 3. Phosphorylate AMPA and NMDA channels to enhance activity 4. Transcription increased to increase AMPA and NMDA receptors at the postsynaptic site |
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What is the effect of microglia-secreted BDNF? |
1. Exacerbates secondary nociceptor excitability by blocking GABA |
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How does BDNF block GABA? |
1. Alteration of gene expression |
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What can chronic high levels of BDNF lead to? |
1. Sprouting of non-nociceptor AB fibers in the dorsal horn 2. New axons make excitatory contacts with secondary nociceptors 3. Permanent allodyina induced |
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What NT activates microglia to release BDNF? |
1. ATP |
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What forms the descending pain control pathway? |
1. Rostral ventromedial medulla 2. Pariqueductal grey matter 3. Hypothalamus 4. Amygdala 5. Anterior cingulate cortex |
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What is the order of the descending pain pathway? |
1. ACC, hypothalamus, and amygdala send axons to the PAG 2. PAG sends axons to RVM 3. RVM sends axons to dorsal horn of spinal cord |
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What is the pain enhancement pathway? |
1. Neurons in amygdala send axons to PAG to activate "on-cells" in RVM |
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What is the role of on-cells? |
1. Increase activity in response to noxious stimuli 2. Enhance pain transmission, leading to hyepralgesia |
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What is the pain inhibition pathway? |
1. Neurons in ACC and hypothalamus send axons to the PAG 2. PAG sends axons to off-cells in RVM |
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What is the role of off-cells? |
1. Inhibits pain transmission in the dorsal horn
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What activates off-cells? |
1. Opioid neurotransmitters 2. Subsequently release opioid NTs onto primary nociceptor afferents and secondary nociceptors 3. Pain transmission blocked to dorsal horn |
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What are the opioid receptor types? |
1. MOR 2. d 3. k 4. ORL1 |
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What is the main target of opioid analgesics? |
1. MOR |
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How does MOR work? |
1. Inhibits AP generation using both presynaptic and postsynaptic mechanisms 2. Postsynaptic involves GIRK 3. Presynaptic involves CaV inhibition
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What is the end result of MOR function? |
1. Glutamate release inhibited 2. Off-cells in RVM inhibited |
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What is the effect of MOR activation on on-cells and secondary nociceptors? |
1. On-cells-- inhibition 2. Secondary nociceptors-- inhibition by GIRK |
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How does MOR activation disinhibit off-cells? |
1. Results from presynaptic inhibition of tonic GABA release by MOR-induced inhibition of CaV channels 2. Reduced GABA release 3. Off-cells depolarized--- increased release of opioid peptides |
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What is the effect of activation of pre-synaptic MOR on glutamate release? |
1. Inhibits glutamate releaser form primary nociceptors by inhibiting CaV |
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How does the placebo effect work in pain? |
1. Engages the body's built-in analgesia pathway to block pain 2. Neurons in hypothalamus, PAG, and RVM activated--- inhibition of pain |
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What drug blocks the placebo effect? |
1. Naloxone--- inhibits MOR |
