1 / 29

How the number of learning trials affects placebo and nocebo responses

tilly
Download Presentation

How the number of learning trials affects placebo and nocebo responses

An Image/Link below is provided (as is) to download presentation Download Policy: Content on the Website is provided to you AS IS for your information and personal use and may not be sold / licensed / shared on other websites without getting consent from its author. Content is provided to you AS IS for your information and personal use only. Download presentation by click this link. While downloading, if for some reason you are not able to download a presentation, the publisher may have deleted the file from their server. During download, if you can't get a presentation, the file might be deleted by the publisher.

E N D

Presentation Transcript

    1. How the number of learning trials affects placebo and nocebo responses Luana Colloca, Predrag Petrovic, Tor D. Wager, Martin Ingvar, Fabrizio Benedetti

    2. Terms Placebo - is a sham or simulated medical intervention that can produce a (perceived or actual) improvement Nocebo – unpleasant response or reaction caused by a placebo drug or condition.

    3. Review! http://www.youtube.com/watch?v=n8y04SrkEZU&feature=related

    4. Analgesic Pathway

    5. Responses to pain induce activity in antinociceptive pathways.  This activity begins when pain information transmitted by the spinothalamic tract reaches the brainstem and thalamus (A above).  Activation of periaqueductal gray and the nucleus raphe magnus induces endorphin and enkephalin release and binding to "opioid" receptor systems.  Sympathetic and parasympathetic influences within the spinal cord facilitate inactivation of antinociceptive pathways.  Most of the endorphin and enkephalin receptors (70%) are localized presynaptically, substantial pain signal attenuation occurs before information reaches the dorsal horn (B above).  Such information may be further attenuated by enkephalin-induced dynorphin activity at the level the cord (C above).   Dynorphin activates -type opioid receptors localized on inhibitory interneurons, activation of which induces release of the inhibitory neurotransmitter GABA. The mechanism by which -opioid receptor activation limits spinal cord cellular activity may be by means of closure of  N-type Ca2+ channels.  Interaction of GABA with its receptor results in dorsal horn neuronal hyperpolarization thus impeding transmission of the pain information.  Reduction of visceral pain may occur particularly by this approach. Enkephalin binds to -type opioid receptors which appear on nociceptive neurons when they actively transmit pain information.  Furthermore, these receptors are often localized on presynaptic vesicles that contain neurotransmitter and following release receptor protein is incorporated into presynaptic membrane.  Active nociceptors, because of preferential binding, are therefore more sensitive than inactive nociceptive receptors to endogenous opiates.  This idea may be relevant in explaining how opioid analgesics appear to relieve ongoing pain but do not prevent sensing of pain subsequent to new injuries.Responses to pain induce activity in antinociceptive pathways.  This activity begins when pain information transmitted by the spinothalamic tract reaches the brainstem and thalamus (A above).  Activation of periaqueductal gray and the nucleus raphe magnus induces endorphin and enkephalin release and binding to "opioid" receptor systems.  Sympathetic and parasympathetic influences within the spinal cord facilitate inactivation of antinociceptive pathways.  Most of the endorphin and enkephalin receptors (70%) are localized presynaptically, substantial pain signal attenuation occurs before information reaches the dorsal horn (B above).  Such information may be further attenuated by enkephalin-induced dynorphin activity at the level the cord (C above).   Dynorphin activates -type opioid receptors localized on inhibitory interneurons, activation of which induces release of the inhibitory neurotransmitter GABA. The mechanism by which -opioid receptor activation limits spinal cord cellular activity may be by means of closure of  N-type Ca2+ channels.  Interaction of GABA with its receptor results in dorsal horn neuronal hyperpolarization thus impeding transmission of the pain information.  Reduction of visceral pain may occur particularly by this approach. Enkephalin binds to -type opioid receptors which appear on nociceptive neurons when they actively transmit pain information.  Furthermore, these receptors are often localized on presynaptic vesicles that contain neurotransmitter and following release receptor protein is incorporated into presynaptic membrane.  Active nociceptors, because of preferential binding, are therefore more sensitive than inactive nociceptive receptors to endogenous opiates.  This idea may be relevant in explaining how opioid analgesics appear to relieve ongoing pain but do not prevent sensing of pain subsequent to new injuries.

    6. Placebo analgesia Some placebo analgesia blocked by naloxone Placebo affect = opioid modulated pathway ACC may control placebo response ACC activity increased by acute pain, opioid analgesia, and placebo analgesia ACC ? PAG Anterior cingulate cortex Anterior cingulate cortex

    7. A model neuronal network explaining placebo analgesia-related activation of ACC neurons. Placebo leads to activation of inhibitory neurons within the ACC. These inhibitory neurons then release an inhibitory neurotransmitter, GABA. GABA acts on postsynaptic GABA receptors to inhibit ACC neurons that are involved in pain perception. In some neurons, endogenous neuropeptides such as enkaphalin (Enk) may also be released to produce similar inhibitory effects (a). Inhibitory neurons may also affect ACC neurons that form descending facilitatory innervations with the spinal cord dorsal horn. Activation of inhibitory neurons within the ACC causes the reduction of descending facilitatory influences. The reduced facilitatory influence on spinal nociceptive transmission therefore produces analgesic effects.A model neuronal network explaining placebo analgesia-related activation of ACC neurons. Placebo leads to activation of inhibitory neurons within the ACC. These inhibitory neurons then release an inhibitory neurotransmitter, GABA. GABA acts on postsynaptic GABA receptors to inhibit ACC neurons that are involved in pain perception. In some neurons, endogenous neuropeptides such as enkaphalin (Enk) may also be released to produce similar inhibitory effects (a). Inhibitory neurons may also affect ACC neurons that form descending facilitatory innervations with the spinal cord dorsal horn. Activation of inhibitory neurons within the ACC causes the reduction of descending facilitatory influences. The reduced facilitatory influence on spinal nociceptive transmission therefore produces analgesic effects.

    8. ACC Nociceptive and Analgesic Effects

    9. Expectation and Placebo Analgesia

    10. Expectation and Placebo Analgesia

    11. Factors Influencing Placebo Cognitive Factors Expectation of pain relief trigger opioids in CNS Classical Conditioning Associations between active analgesics, pain relief, and therapeutic surroundings Responders and Non-responders

    12. Materials Electric stimulation to foot randomized which foot 100 microseconds Yellow, green, or red light before shock

    13. Methods Group 1: one session of conditioning Group 2: four sessions of conditioning Both groups: Non-painful stimuli test Painful stimuli test

    14. Test Types Non-painful Intensity of stimulation above Aß fiber threshold but below nociceptive Ad and C fiber threshold Painful Above nociceptive Ad and C fiber threshold levels

    15. VAS Scoring Subjects scored perception and pain (0-10 VAS) T and t levels prior to testing Pain rated after conditioning and test (which convey non-painful tactile information) Visual analogue scale(which convey non-painful tactile information) Visual analogue scale

    18. Testing Procedure

    19. Results (group 1)

    20. Results (group 1)

    21. Results (group 2)

    22. Results (group 2) Speculate that there is ACC inhibition occuring to modify perception of Green Light placebo… Speculate that there is ACC inhibition occuring to modify perception of Green Light placebo…

    23. Placebo/Nocebo relationship Correlation for group 1 pain conditionCorrelation for group 1 pain condition

    24. Placebo/Nocebo relationship Negative correlation for group 2 no pain conditionNegative correlation for group 2 no pain condition

    25. Placebo/Nocebo relationship No correlation for pain conditionNo correlation for pain condition

    26. Average VAS Response

    27. Results Summery Short conditioning period No lasting effects for non-painful condition Only painful nocebo effect endured Long conditioning period Both placebo and nocebo effects endured

    28. Discussion Conditioning is needed for placebo and nocebo effects Both conscious and subconscious learning shape behavior Past experience with pain relief effect the efficacy of treatment Clinical usage of placebo and avoidance of nocebo

    29. Unrelated… http://www.youtube.com/watch?v=qIoG4PlEPtY

More Related