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Placebos and Painkillers: Is Mind as Real as Matter? Luana Colloca and Fabrizio Benedetti 2005 in Nature Reviews Neuros

Placebos and Painkillers: Is Mind as Real as Matter? Luana Colloca and Fabrizio Benedetti 2005 in Nature Reviews Neuroscience. Jess Benjamin Steele Taylor Celeste Parot January 30, 2008. http://www.annkullberg.com/Shows/2003/Hild.jpg.

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Placebos and Painkillers: Is Mind as Real as Matter? Luana Colloca and Fabrizio Benedetti 2005 in Nature Reviews Neuros

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  1. Placebos and Painkillers: Is Mind as Real as Matter?Luana Colloca and Fabrizio Benedetti2005 in Nature Reviews Neuroscience Jess Benjamin Steele Taylor Celeste Parot January 30, 2008 http://www.annkullberg.com/Shows/2003/Hild.jpg

  2. Nociceptive neuron stimulated through compression, heat, or chemical irritation in periphery Nociceptive neuron synapses on projection neurons and interneuron networks in the dorsal horn Myelinated neospinothalamic axons project fine information to thalamic relay nucleus Thalamus relays to primary and associative somatonsensory cortices Ultimately these regions project back to brainstem, prefrontal, limbic system, and thalamus Slow unmyelinated paleospinothalamic axon collaterals project crude information to multiple targets in brainstem and limbic system Emotional and behavioral responses to painful stimuli Vaguely localized throbbing pain http://www.scripps.edu/cb/patapoutian/nocisensor.jpg Pain Overview http://www.laesieworks.com/spinal/pict/SpinalCord.jpg

  3. Nociceptive neuron stimulated through compression, heat, or chemical irritation in periphery Nociceptive neuron synapses on projection neurons and interneuron networks in the dorsal horn Myelinated neospinothalamic axons project fine information to thalamic relay nucleus Thalamus relays to primary and associative somatonsensory cortices Ultimately these regions project back to brainstem, prefrontal, limbic system, and thalamus Slow unmyelinated paleospinothalamic axon collaterals project crude information to multiple targets in brainstem and limbic system Emotional and behavioral responses to painful stimuli Vaguely localized throbbing pain Pain Overview www.nursece.com/onlinecourses/imagesPain/Fig2.gif

  4. Nociceptive neuron stimulated through compression, heat, or chemical irritation in periphery Nociceptive neuron synapses on projection neurons and interneuron networks in the dorsal horn Myelinated neospinothalamic axons project fine information to thalamic relay nucleus Thalamus relays to primary and associative somatonsensory cortices Ultimately these regions project back to brainstem, prefrontal, limbic system, and thalamus Slow unmyelinated paleospinothalamic axon collaterals project crude information to multiple targets in brainstem and limbic system Emotional and behavioral responses to painful stimuli Vaguely localized throbbing pain Pain Overview www.doctordeluca.com/Library/Pain/CP1NewDisease2K.htm

  5. Nociceptive neuron stimulated through compression, heat, or chemical irritation in periphery Nociceptive neuron synapses on projection neurons and interneuron networks in the dorsal horn Myelinated neospinothalamic axons project fine information to thalamic relay nucleus Thalamus relays to primary and associative somatonsensory cortices Ultimately these regions project back to brainstem, prefrontal, limbic system, and thalamus Slow unmyelinated paleospinothalamic axon collaterals project crude information to multiple targets in brainstem and limbic system Emotional and behavioral responses to painful stimuli Vaguely localized throbbing pain Pain Overview www.doctordeluca.com/Library/Pain/CP1NewDisease2K.htm

  6. Centrally Mediated Pain Regulation • Appropriate activation of periaqueductal grey matter (PAG) in mesencephalon and opioid networks in thalamus http://www.sciencemag.org/cgi/content/full/288/5472/1769 • Some Psychobiological Stimuli Associated With Internally Generated Analgesia: • Conditioned Anticipation of Pain Relief • Pain in Other Areas • Emotional Well Being • Concentration/Meditation • Hypnosis • Gate-Mediated Mechanical Stimuli http://www.doctordeluca.com/Library/Pain/Graphics/CP1NewDis-F2.bmp

  7. Centrally Mediated Pain Regulation • Appropriate activation of periaqueductal grey matter (PAG) in mesencephalon occurs • PAG projects into nucleus raphe magnus (serotonergic) and locus ceruleus (noradrenergic) in rostral ventral medulla (RVM) • Serotonergic innervation of inhibitory opiodergic neurons • Dorsal Horn Interneurons • Central Pain Processing Regions (notice the inhibition of retrograde substance p release into the periphery!) http://www.mona.uwi.edu/fpas/courses/physiology/neurophysiology/PainRapheFeedback.jpg • Opiod-Mediated Inhibition Occurs Via: • 1) K+ channel Activation • (Hyperpolarization) • 2) Ca2+ channel Deactivation • (Reduced NT Release) • 3) Other Mechanisms

  8. Opioid Reinforcement Through Dopamine Signaling • Reinforcement/addiction may be associated with impact on dopamine signaling • Opiod mediated inhibition of GABAergic neurons tonically inhibiting DAergic neurons in ventral tegmental area (VTA) of mesencephalon (off + off = on) • DA release into nucleus accumbens (reward center) and cognitive cortices thebrain.mcgill.ca/.../i_03_cr_que_1a.jpg

  9. Remfentanil is an opioid agonist Comparison of brain imaging during remfentanil exposure and placebo-analgesia reveals similarities in the activated pathways This supports the opioid hypothesis of the placebo-analgesic response Isolating the Placebo Analgesia Pathways:The Chemical Players Functional MRI www.ym.edu.tw/rcinn/images/cp1-fg3.png Positron Emission Tomography http://www.nida.nih.gov/NIDA_notes/NNVol16N2/Positron.jpg

  10. Proglutamide: a CCK antagonist that enhances placebo analgesia due to the facilitation of expectation pathways Based on double-blind paradigm one can erroneously conclude that Proglutamide has intrinsic analgesic activity PET imaging and open-hidden paradigm provides more accuracy Therefore, Proglutamide IS the disturbance in double-blind studies Isolating the Placebo Analgesia Pathways:The Chemical Players http://www.nature.com/nrn/journal/v6/n7/fig_tab/nrn1705_F1.html

  11. Naloxone is the prototypical opioid antagonist (and OD antidote) Naloxone reliably blocks placebo induced analgesia But, only through conditioning with previous opioid-analgesic responses Non-opiod associated placebo effects are naloxone insensitive Sumatriptan (5-HT agonist) Therefore, naloxone also blocks side-effects accompanying opioid-operating placebo responses Respiratory depression Cardiac depression Disturbance: In a double-blind study, naloxone appears to have a hyperalgesic effect (but not in open-hidden paradigms) Isolating the Placebo Analgesia Pathways:The Chemical Players

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