SBP Lecture 5

What are the nuclei of the spinal trigeminal nuclei?
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Nociception is not the _________ for everyone.same. We all have our own specific threshold and it can be due to sensitization.In the medullary dorsal horn. 2nd order Nociceptive specific neurons respond only to _________ stimuli.painful. They would not receive info from nerves that are not nociceptive. This is how we can have pain and another sensation at the same time. An example would be scrapping your arm against a sharp object. You will feel the mechanoreceptors and the pain from nociceptive.Another cell type in the Medullary dorsal horn (2nd order neuron) can respond to both painful and non-painful stimuli.wide dynamic range neurons.Wide dynamic range neurons neurons in the medullary dorsal horn have ___________ receptive fields.LargeNociceptive specific neurons in the medullary dorsal horn also have __________ receptive fields.largeSeven different afferent inputs to MDH neurons. This input from several primary/presynaptic neurons to an individual neuron is called __________.convergence.The medullary dorsal horn is a layered structure. Nociceptive specific terminate mostly in the ___________ layers. Non-nociceptive terminate mostly in ________ layers. Overlap in layers ____ and ____.superficial (1, 2) Deep (3, 4, 5) layers 2 and 5How many different types of neurons are there in the dorsal horn of the CNS (medulla)?2The medullary dorsal horn has a high degree of _______________.convergenceConvergence of peripheral afferents have different receptive fields all over the _________.head. cutaneous, joints, muscle, tooth pulp, and other nerves like superior laryngeal nerve.Can referred pain be explained by convergence in the MDH?yes, partially. Pain and non-pain afferents converge in the "pain signaling" neuron but referred pain only occurs under pathological conditions and is not a normal sensation. Perhaps something is preventing the activation of convergent input in the MDH under normal conditions.Does peripheral sensitization explain referred pain?Not entirely, peripheral sensitization mostly increases C-fiber sensitivity. It does not explain large areas of pain (increased receptive fields). Following sever nerve injury, there could be ephaptic connections between pain and non-pain fibers that could enlarge receptive fields)So referred pain is simply _______ fully understood.not fully understood.Central sensitization can occur in 2 ways:hyperalgesia and allodynia. These are the same as PNS but happens in completely different way.Hyperalgesia in the CNS happens when a __________neuron sends signals that is capture as more pain than there should be.nociceptiveAllodynia happens when a __________ neuron is synapsing/converging with a wide dynamic range neuron and there is pain when there shouldn't be.mechanoreceptor, like a Abeta fiber. This is like a really bad sunburn where mechanoreceptors can send signals and cause pain.C-fibers in the PNS can be sensitized by ___________. These can respond to the inflammation and send signals to the medullary dorsal horn and cause ___________.inflammation. depolarization.LTP (long term potentiation) can cause hyperalgesia because _______ fibers can then release glutamate onto the WDR neuron in the MDH and cause pain.AbetaAnother method of central sensitization is that we can also increase the number of _________ that receive the signal on the 2nd order neurons. This is known as ___________ translational change in ion channels.receptors. post-translationalThis peripherally induced central sensitization also allows GluR1 ________ entry into the 2nd order neuron.Ca2+Referred pain is explained by a single afferent innervating _________ areas.multipleMore of referred pain is explained by afferents converging in the ________.medullary dorsal horn.PNS inflammation can sensitize the ___________. This can cause __________ side pain due to crossing over of the sensitization.CNS. Contralateral__________ cells can also contribute to central sensitization. They can become activated by injury or _________. Recall that they are like immune cells in the body. They can secrete _________ that can also stimulate more glia in a feedback mechanism.Glial cells inflammation neurotransmittersFor central sensitization, ________ can increase the presynaptic release of glutamate( in the actual presynaptic neuron). Suppression of astrocytic _________ reuptake. Release of glutamate from astrocytes, is capable of increasing the excitability of nearby __________.IL1B from the neuron glutamate neurons as well.__________ from the astrocytes can also increase Ca+ influx via binding to glycine sites (excitatory like glutamate) on NMDA receptors on postsynaptic neurons.D-serineAstrocytic release of _______ can also increase postsynaptic excitability via activation of _________-gated purinergic receptors (P2x4R and P2X7R).ATP. Ligand.TNFalpha and IL1B increase the translocation of _______ receptors to the postsynaptic membrane and increase their conductance via and ERK-dependent pathway.NMDAProinflammatory cytokines have been linked to increased expression and activation of ____ receptors at he excitatory synapses.AMPA.Reactive _______ have increased expression of receptors for various neurotransmitters and chemokines, which can induce the further release of proinflammatory cytokines upon stimulation, thereby perpetuating neuronal excitation.microglia.Take aways from glial driven central sensitization. Microglial cells are sensitive to neurotranmitter/modulators which can bind to __________ and ___________ receptors.ionotropic and metabotropic receptors.Glial cells secrete pro-inflammatory mediators that have an ______ feedback. Can affect release of neurotranmsitters in the presynaptic neuron. Can affect 2nd messenger cascades to open/translocate metabotropic channels. Can increase expression and activation of ionotropic receptors.autocrine.Glia can increase the amount of synaptic neurotransmitters in the clefts, thereby increasing neuron ___________.excitability.Glial cells can attenuate nociceptive inhibition. Within inhibitory synapses of the spinal cord dorsal horn, the effects of these mediators ultimately lead to a reduction in __________ neurotransmission, which further facilitates central sensitization.inhibitoryExample of this is IL-1B can mediate a decrese in the astrocytic uptake of ___________. Which can lead to decreased availability of glutamine for GABA synthesis.glutamatePNS and CNS sensitization can lead to ___________ pain which involves the brain's interpretation.chronicThe brain's interpretation of pain depends on such things like: context, cognitive set (hypervigilance), __________, chemical and structure, injury.moodThe ________ is the primary relay center for transmission to brain areas for processing.thalamusThe anterior cingulate cortex (limibic) processes the _______ component and initiates coping behavior.emotional/afferentThe prefrontal cortex processes the meaning of pain and what we should ____.doThe insular cortex is responsible for triggering the ________ instinct. Only present in the threat of pain, lack of oxygen, etc.survivalHippocampus enables us toremember.The amygdala helps usmake a decision.Dental anxiety can _______ a patient's sense of pain.hightenEmpathy for pain activates the anterior cingulate and the __________.insulaThere is an anatomical difference between emotional component of pain (empathy) and __________ component of pain.somatosensory component. Empathy does not activate SI or SII (somatosensory)We do a lot of testing to rule out the placebo effect and we look specifically at the _________ cortex.anterior cingulate cortex.Desending control of pain: what sites help modulate pain?forebrain (anterior cingulate cortex) midbrain (periaquaductal grey) rostral ventromedial medullaThese 3 sites in the descending control of pain, release ____________.endogenous opioids.The PAG is normally inhibited by the neurotransmitter __________. Opioids prevent it's release.GABA.After activation, PAG neurons activate serotonergic neurons in the forebrain and noradrenergic neurons in the medulla. This stimulates enkepthalinergic interneurons, which inhibits _______ perception.pain