Ignite Creation Date:
2024-05-06 @ 11:08 AM
Last Modification Date:
2024-10-26 @ 12:41 PM
Study NCT ID:
NCT03446456
Status:
RECRUITING
Last Update Posted:
2024-03-28
First Post:
2018-01-16
Brief Title:
Vasopressin and Pain Perception in the Brain
Sponsor:
University of Maryland Baltimore
Organization:
University of Maryland Baltimore
Study Overview
Official Title:
The Influence of Vasopressin on Observational Learning of Placebo Analgesia
Status:
RECRUITING
Status Verified Date:
2024-01
Last Known Status:
None
Delayed Posting:
No
If Stopped, Why?:
Not Stopped
Has Expanded Access:
False
If Expanded Access, NCT#:
N/A
Has Expanded Access, NCT# Status:
N/A
Acronym:
None
Brief Summary:
The feeling of pain is not just a sensory experience but is also influenced by emotions beliefs and expectations making pain a highly subjective experience This is evident in clinical practice where the behavior of the physician and the treatment context can strongly influence the pain experience of patients Research has shown that patients expectation that a treatment will reduce pain influences individual perception of pain even if the treatment has no active ingredient The expectancy-induced analgesia emerges due to a modulation of the individual pain experience of patients by an engagement of endogenous inhibitory systems in the central nervous system
The development of expectancy-induced analgesia can be generated in several ways The investigators have previously demonstrated that social information and observational learning eg the patient observes analgesia in another person receiving a treatment can lead to expectancy-induced analgesia and pain reduction However the neural mechanisms mechanisms in the brain of how these expectancies are acquired and the neural mechanisms of analgesia induced by observational learning are unknown
The investigators recently established a procedure to investigate neural mechanisms of observational learning in placebo analgesia Here the investigators propose to investigate the influence of vasopressin a neurotransmitter that is important for social interaction on observational learning
The investigators will use functional magnetic resonance imaging fMRI a non-invasive method to investigate neural activity in humans Participants will either receive vasopressin or saline with a nasal spray During fMRI scanning participants will then undergo an observational learning phase where the study participants will learn the experience of analgesia in another person through a video and a testing phase where participants will perceive painful stimulations with the same cues as the observational phase The comparison of the vasopressin group and the saline group will allow us to investigate how vasopressin influences behavioral effects of observational learning on pain perception as well as its effect on the neural processing of observational learning
A better understanding of how the human brain processes observationally-induced analgesia would allow us to improve the therapeutic context of pain treatments by increasing the contextual factors which help patients cope with pain
The development of expectancy-induced analgesia can be generated in several ways The investigators have previously demonstrated that social information and observational learning eg the patient observes analgesia in another person receiving a treatment can lead to expectancy-induced analgesia and pain reduction However the neural mechanisms mechanisms in the brain of how these expectancies are acquired and the neural mechanisms of analgesia induced by observational learning are unknown
The investigators recently established a procedure to investigate neural mechanisms of observational learning in placebo analgesia Here the investigators propose to investigate the influence of vasopressin a neurotransmitter that is important for social interaction on observational learning
The investigators will use functional magnetic resonance imaging fMRI a non-invasive method to investigate neural activity in humans Participants will either receive vasopressin or saline with a nasal spray During fMRI scanning participants will then undergo an observational learning phase where the study participants will learn the experience of analgesia in another person through a video and a testing phase where participants will perceive painful stimulations with the same cues as the observational phase The comparison of the vasopressin group and the saline group will allow us to investigate how vasopressin influences behavioral effects of observational learning on pain perception as well as its effect on the neural processing of observational learning
A better understanding of how the human brain processes observationally-induced analgesia would allow us to improve the therapeutic context of pain treatments by increasing the contextual factors which help patients cope with pain
Detailed Description:
The purpose of this research is to investigate how vasopressin AVP influences the neural mechanisms associated with observationally-induced analgesia More specifically the investigators will determine how observing another person experiencing analgesia shapes subsequent behavioral and neural responses to painful stimulations
Aim 1 To investigate how AVP influences the neural mechanisms associated with observationally-induced analgesia
Hypothesis 1 The investigators expect that AVP will boost activation in brain regions involved in social cognition
The overall objective is to determine the effect of AVP on brain mechanisms associated with observationally-induced analgesia This experiment has a between-subject study design Participants will be randomized into an AVP group and a control group The experimenter as well as the participant will be blinded regarding the allocation of the participant Participants in the AVP group will receive intranasal AVP and the participants in the control group will receive intranasal saline before the fMRI experiment Participants have 50 chance of being placed in either group The experiment in the fMRI scanner is divided into two phases an observational phase in which participants will observe a video of a demonstrator experiencing analgesia and a testing phase in which study participants will receive heat pain to investigate how pain perception was influenced During both phases there will be a placebo condition pain with the expectation of having received a treatment and a control condition pain without the expectation of having received a treatment All participants will complete both phases including the observational and testing phase
Expectancy of analgesia related to the act of receiving a treatment eg a painkiller can reduce pain perception even if this treatment is in fact an inert substance eg placebo Expectancies about analgesic treatments can be acquired in several different ways including direct experience of analgesia ie the patient learns that after taking a specific drug pain will decrease verbal instructions ie the doctor tells the patient that a specific drug will reduce pain or social observation ie the patient observes pain relief in another patient after this patient took a specific drug
The direct experience of pain relief in the context of treatment cues ie conditioning reduces subsequent pain perception when the same treatment cues are present The neural underpinnings of how treatment expectancies are acquired during conditioning have been investigated previously These studies indicate that the prefrontal cortex is involved in learning treatment expectations in the context of conditioned analgesic effects
However these expectancies can also be acquired by observing others Our group was the first to demonstrate that analgesia can be triggered by observing another person that experiences analgesia This finding has been corroborated with additional studies by our group and other groups In these experiments participants acquire expectancies of analgesia not by experiencing pain relief themselves but rather by observing another person the demonstrator experiencing analgesia after receiving a certain analgesic treatment actually a sham treatment These placebo manipulations generate expectancies which lead to placebo effects of similar sizes that those shown through direct experience via conditioning paradigms
Even though previous research has focused on the direct experience of pain relief within a treatment context social psychology suggests that most human behaviors are in fact modulated by sociality and learned by observing others The investigators recently established a paradigm to investigate neural mechanisms of observational learning in placebo analgesia The preliminary data analysis unpublished data suggests that while participants are observing someone else experiencing less pain due to an analgesic treatment brain regions associated with mentalizing processes such as left and right temporoparietal junction TPJ and medial prefrontal cortex mPFC show increased activation However the underlying neurotransmitter systems are unknown Here the investigators aim to investigate how AVP modulates this network of brain regions AVP is a likely candidate system because recently it has been associated with placebo analgesia by my current mentors lab is involved in controlling a wide variety of social behaviors and has been shown to critically modulate TPJ activity The investigators expect that AVP will lead to increased activation of the mentalizing network during observational learning and therefore to increased placebo analgesia as a result of the observational learning In order to investigate this the investigators will perform a similar observational learning study in a group receiving intranasal AVP and a control group receiving intranasal saline
Background Clinical outcomes are not just related to pharmacological substances but also to the context in which a treatment is given as well as expectancies fears desires and beliefs of the patient The beneficial effects on health related outcome changes due to the treatment context and not due to specific actions of a drug are known as placebo effects In the field of pain the reduction of pain perception due to placebo effects is called placebo analgesia or expectancy-induced analgesia
Previous research shows that in placebo analgesia informational cues of the treatment context generate the expectancy of pain relief due to a treatment These expectations can be acquired through several ways including learning through direct experience ie conditioning verbal instruction or observation of others
Several studies investigated the influence of direct experience of analgesia using conditioning paradigms on placebo effects These studies show that conditioning creates more robust placebo effects than verbal suggestions alone and that the magnitude of experienced pain relief and the duration influence subsequent placebo effects
On the neural level placebo effects on pain perception are mediated by the descending pain modulatory system Endogenous opioids are involved in the pain descending modulation systems and placebo analgesia can be substantially reduced by opioid antagonists Several studies implicate functional connectivity between the rostral anterior cingulate and the periaqueductal gray a region critical for descending pain modulation and placebo analgesia Additionally there is considerable evidence that prefrontal regions especially the dorsolateral prefrontal cortex DLPFC are critically involved in placebo analgesia The prefrontal cortex consistently shows higher activations related to the anticipation of analgesia and experience of pain relief induced by a placebo manipulation and is involved in the acquisition of expectancies during conditioning of placebo analgesia
Therefore the current understanding is that the prefrontal cortex maintains and updates expectancies regarding pain and that these prefrontal regions influence the experience of pain by activating the descending pain modulatory system
The influence of social learning on placebo analgesia has been investigated to a lesser degree Recent research suggests that placebo analgesia can also be induced by observational learning however the neural neurotransmitter systems underpinning observationally-induced placebo analgesia have not yet been investigated
Rationale To harness the placebo effects in clinical contexts it is important to understand how placebo effects arise and are maintained Previous neuroscience research has primarily focused on conditioning paradigms however human behaviors are affected by social learning Social learning refers to learning about the environment due to information gained by observing others Our overall hypothesis is that AVP will increase neural activation in regions related to social cognition during observational learning Our objective is to determine the interplay of AVP and observationally-induced analgesia using an fMRI approach fMRI is a noninvasive technique to measure changes in blood oxygenation in the brain enabling us to draw inferences about the localization and extend of neural activation associated with specific events and cues including the perception of experimental painful stimulations and modulation The investigators designed an experiment to be performed behaviorally and with fMRI measurements in order to determine the interplay of AVP and observationally-induced analgesia
Significance This experiment will advance our understanding of endogenous processes associated with observationally-induced analgesia and the factors that influences pain processing A better understanding of how treatment expectancies formed through social observation influence the individual experience of pain is significant in several ways First it will allow a better understanding of the contextual factors shaping pain and responses to treatments in clinical settings Second knowledge about the neural processes associated with endogenous pain relief might lead to novel developments in pain therapeutic strategies Third the investigators anticipate generating findings that will advance our knowledge of how cognitive processes ie expectancy are represented in the brain and how these factors influence human social behaviors
Aim 1 To investigate how AVP influences the neural mechanisms associated with observationally-induced analgesia
Hypothesis 1 The investigators expect that AVP will boost activation in brain regions involved in social cognition
The overall objective is to determine the effect of AVP on brain mechanisms associated with observationally-induced analgesia This experiment has a between-subject study design Participants will be randomized into an AVP group and a control group The experimenter as well as the participant will be blinded regarding the allocation of the participant Participants in the AVP group will receive intranasal AVP and the participants in the control group will receive intranasal saline before the fMRI experiment Participants have 50 chance of being placed in either group The experiment in the fMRI scanner is divided into two phases an observational phase in which participants will observe a video of a demonstrator experiencing analgesia and a testing phase in which study participants will receive heat pain to investigate how pain perception was influenced During both phases there will be a placebo condition pain with the expectation of having received a treatment and a control condition pain without the expectation of having received a treatment All participants will complete both phases including the observational and testing phase
Expectancy of analgesia related to the act of receiving a treatment eg a painkiller can reduce pain perception even if this treatment is in fact an inert substance eg placebo Expectancies about analgesic treatments can be acquired in several different ways including direct experience of analgesia ie the patient learns that after taking a specific drug pain will decrease verbal instructions ie the doctor tells the patient that a specific drug will reduce pain or social observation ie the patient observes pain relief in another patient after this patient took a specific drug
The direct experience of pain relief in the context of treatment cues ie conditioning reduces subsequent pain perception when the same treatment cues are present The neural underpinnings of how treatment expectancies are acquired during conditioning have been investigated previously These studies indicate that the prefrontal cortex is involved in learning treatment expectations in the context of conditioned analgesic effects
However these expectancies can also be acquired by observing others Our group was the first to demonstrate that analgesia can be triggered by observing another person that experiences analgesia This finding has been corroborated with additional studies by our group and other groups In these experiments participants acquire expectancies of analgesia not by experiencing pain relief themselves but rather by observing another person the demonstrator experiencing analgesia after receiving a certain analgesic treatment actually a sham treatment These placebo manipulations generate expectancies which lead to placebo effects of similar sizes that those shown through direct experience via conditioning paradigms
Even though previous research has focused on the direct experience of pain relief within a treatment context social psychology suggests that most human behaviors are in fact modulated by sociality and learned by observing others The investigators recently established a paradigm to investigate neural mechanisms of observational learning in placebo analgesia The preliminary data analysis unpublished data suggests that while participants are observing someone else experiencing less pain due to an analgesic treatment brain regions associated with mentalizing processes such as left and right temporoparietal junction TPJ and medial prefrontal cortex mPFC show increased activation However the underlying neurotransmitter systems are unknown Here the investigators aim to investigate how AVP modulates this network of brain regions AVP is a likely candidate system because recently it has been associated with placebo analgesia by my current mentors lab is involved in controlling a wide variety of social behaviors and has been shown to critically modulate TPJ activity The investigators expect that AVP will lead to increased activation of the mentalizing network during observational learning and therefore to increased placebo analgesia as a result of the observational learning In order to investigate this the investigators will perform a similar observational learning study in a group receiving intranasal AVP and a control group receiving intranasal saline
Background Clinical outcomes are not just related to pharmacological substances but also to the context in which a treatment is given as well as expectancies fears desires and beliefs of the patient The beneficial effects on health related outcome changes due to the treatment context and not due to specific actions of a drug are known as placebo effects In the field of pain the reduction of pain perception due to placebo effects is called placebo analgesia or expectancy-induced analgesia
Previous research shows that in placebo analgesia informational cues of the treatment context generate the expectancy of pain relief due to a treatment These expectations can be acquired through several ways including learning through direct experience ie conditioning verbal instruction or observation of others
Several studies investigated the influence of direct experience of analgesia using conditioning paradigms on placebo effects These studies show that conditioning creates more robust placebo effects than verbal suggestions alone and that the magnitude of experienced pain relief and the duration influence subsequent placebo effects
On the neural level placebo effects on pain perception are mediated by the descending pain modulatory system Endogenous opioids are involved in the pain descending modulation systems and placebo analgesia can be substantially reduced by opioid antagonists Several studies implicate functional connectivity between the rostral anterior cingulate and the periaqueductal gray a region critical for descending pain modulation and placebo analgesia Additionally there is considerable evidence that prefrontal regions especially the dorsolateral prefrontal cortex DLPFC are critically involved in placebo analgesia The prefrontal cortex consistently shows higher activations related to the anticipation of analgesia and experience of pain relief induced by a placebo manipulation and is involved in the acquisition of expectancies during conditioning of placebo analgesia
Therefore the current understanding is that the prefrontal cortex maintains and updates expectancies regarding pain and that these prefrontal regions influence the experience of pain by activating the descending pain modulatory system
The influence of social learning on placebo analgesia has been investigated to a lesser degree Recent research suggests that placebo analgesia can also be induced by observational learning however the neural neurotransmitter systems underpinning observationally-induced placebo analgesia have not yet been investigated
Rationale To harness the placebo effects in clinical contexts it is important to understand how placebo effects arise and are maintained Previous neuroscience research has primarily focused on conditioning paradigms however human behaviors are affected by social learning Social learning refers to learning about the environment due to information gained by observing others Our overall hypothesis is that AVP will increase neural activation in regions related to social cognition during observational learning Our objective is to determine the interplay of AVP and observationally-induced analgesia using an fMRI approach fMRI is a noninvasive technique to measure changes in blood oxygenation in the brain enabling us to draw inferences about the localization and extend of neural activation associated with specific events and cues including the perception of experimental painful stimulations and modulation The investigators designed an experiment to be performed behaviorally and with fMRI measurements in order to determine the interplay of AVP and observationally-induced analgesia
Significance This experiment will advance our understanding of endogenous processes associated with observationally-induced analgesia and the factors that influences pain processing A better understanding of how treatment expectancies formed through social observation influence the individual experience of pain is significant in several ways First it will allow a better understanding of the contextual factors shaping pain and responses to treatments in clinical settings Second knowledge about the neural processes associated with endogenous pain relief might lead to novel developments in pain therapeutic strategies Third the investigators anticipate generating findings that will advance our knowledge of how cognitive processes ie expectancy are represented in the brain and how these factors influence human social behaviors
Study Oversight
Has Oversight DMC:
None
Is a FDA Regulated Drug?:
True
Is a FDA Regulated Device?:
False
Is an Unapproved Device?:
None
Is a PPSD?:
None
Is a US Export?:
True
Is an FDA AA801 Violation?:
None