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Human Behaviors Related to the Expectation of Pain

Physiological Studies in Healthy Subjects, Chronic Pain Patients and in Patients Undergoing Neurosurgical Procedures of Human Forebrain Mechanisms Mediating Somatic Sensation, Motor Control and Neurological Disorders

Status
Terminated
Phases
NA
Study type
Interventional
Source
ClinicalTrials.gov
Registry ID
NCT03739645
Enrollment
32
Registered
2018-11-14
Start date
2020-08-01
Completion date
2023-10-01
Last updated
2025-05-25

For informational purposes only — not medical advice. Sourced from public registries and may not reflect the latest updates. Terms

Conditions

Fear Pain

Keywords

fear, pain, conditioning, skin conductance response, Ratings of Pain and Conditioning, Eye position metrics

Brief summary

The conditioned expectation of pain is an important aspect of pain-related disability produced by environments and stimuli associated with a painful injury on the job, although the neuroscience of this expectation is unclear. We will develop and use novel objective methods for measurement of expectation and threat related attention. The results of this study may lead to testable hypotheses regarding the psychological basis of the fear of pain, threat and task related attention. We will also use these results, and development of novel autonomic and ratings metrics for state and trait anxiety as well as threat and task related attention which could be used as an instrumented test for diagnosis and management of PTSD and anxiety disorders. .

Detailed description

The conditioned expectation or fear of pain often results in disability produced by stimuli related to a painful injury on the job, although there are questions about attentional and anxiety related expectation. Conditioned expectation in humans can be produced by a protocol that consists of a train of two visual conditioning stimuli, one of which is paired (CS+) with a painful laser pulse unconditioned stimulus (US), while the other is not. This protocol will be used to study the expectation of pain in this study, and its relationship to task and threat related attention measured by eye position and to anxiety, task directed sustained attention, and scalp EEG metrics. These results may also be used in an instrumented test for the diagnosis and management of PTSD and anxiety disorders. EEG studies may clarify the relationship of unpleasantness (valence) and the ability of stimuli to command attention (salience) of the conditioned and unconditioned stimuli which which are significant but under studied aspects of the fear of the pain. Studies of scalp EEG activation and functional connectivity will be used to estimate global properties of the forebrain networks involved in the fear of pain, as well as the valence and the salience) of the conditioned and unconditioned stimuli. Activations are measured by the proportion of electrodes over a quadrant or lobe of the scalp a significant ratio of electrical power following an event over baseline (event related spectral perturbation, ERSP). Functional connectivity will be measured by causal interactions following an event over baseline. The approach of this protocol is that causal interactions are based upon causal influences by an approach based upon the concept of linear predictability. Briefly, a signal Y is said to exert an influence upon signal X when the predication error of the X is reduced by adding the past information of Y (causal interaction). The signals from any two quadrants or lobes will be analyzed by event related causality to determine the magnitude and direction of causal interactions between the two to determine fear and pain related directed interactions related to aversive conditioning. Our Preliminary Data shows EEG activations in global distributed forebrain networks for the expectation of pain are consistent with the evidence of studies of anatomic projections and functional MRI (fMRI) signals. These models including our Preliminary Data from intracranial recordings identify structures in the medial temporal lobe (amygdala and hippocampus) which are involved in expectation of pain, while EEG suggests global activations related to valence and salience of conditioned and unconditioned stimuli. The premise of this study is that novel autonomic and eye position metrics will measure state and trait anxiety as well as threat and task related attention to parse out the experience and anticipation of pain.

Interventions

BEHAVIORALSkin conductance levels and slopes over time in conditioned fear as metrics.as metrics for anxiety

After fear conditioning the cue induces autonomic responses like skin conductance and cognitive ratings like expectancy of the unconditioned stimulus after cueing or conditioning. Activity across blocks in the conditioning stage shows that the skin conductance can be described by levels, and slopes which might be related to state anxiety and trait anxiety (Spielberger trait and state anxiety inventory or questionnaire). These skin conductance measures may be concrete metrics for psychological processes in healthy subjects. We will carry out a partial correlation analysis of levels, state anxiety and trait anxiety, and then a similar analysis of slopes, state anxiety and trait anxiety. These results may show that concrete skin conductance levels and slopes are related to metrics of subjective self report measures of state and trait anxiety.

Sponsors

University of Maryland
CollaboratorOTHER
National Institute of Neurological Disorders and Stroke (NINDS)
CollaboratorNIH
Johns Hopkins University
Lead SponsorOTHER

Study design

Allocation
NA
Intervention model
SINGLE_GROUP
Primary purpose
BASIC_SCIENCE
Masking
NONE

Intervention model description

Analysis of eye position and skin conductance levels will be examined to identify attentional and anxiety related processes for the fear of pain during the conditioned stage. Correlation of skin conductance levels versus slopes during the conditioning stage with state versus trait anxiety will be taken as confirmatory evidence. Power analysis for a two-way ANOVA was conducted to determine a sufficient sample size using an alpha of 0.05, power 0.80, a high effect size (pilot data indicate η2 values for main effects \> 0.5). Based on these assumptions, we conservatively use a sample size of 40.

Eligibility

Sex/Gender
ALL
Age
16 Years to 88 Years
Healthy volunteers
Yes

Inclusion criteria

* Man or woman between 18 and 80 years of age. * Fluent speaker of English. * Undergoing seizure monitoring at Hopkins Hospital through intracranial electrodes. * Possess ability to understand study procedures and comply with them for the entire length of the study; * Women of childbearing age must use pharmacological contraception (oral or patch) for the duration of the study follow-up.

Exclusion criteria

* Inability or unwillingness of individual to give written informed consent. Presence of any neurological disease other than epilepsy which is unstable or is not optimally treated. * Presence of a significant abnormality on routine neuropsychological testing. * Presence of any medical or psychiatric disease which is unstable or is not optimally treated. Presence of an abnormal MRI scan except for Normal variants or Medial Temporal Sclerosis (altered pathology and MRI signal in temporal lobe). * Women who are pregnant or women of childbearing capacity who may become pregnant (i.e. not using contraception). * Presence of generalized seizures, or reflex seizures i.e. triggered by a sensory stimulus. * Presence of a language or hearing impairment. * Non-English speakers.

Design outcomes

Primary

MeasureTime frameDescription
Skin Conductance Response5 seconds post conditioned stimulusConcrete metric is skin conductance response to painful laser pulse stimulus measured in microSiemens. Higher values mean more emotional arousal or stress. All participants experienced two types of conditioned stimuli, one stimulus signaled danger and the other safety. Only during the danger stimulus would the participant receive a laser pulse.
State Anxiety as Assessed by the Spielberger State-Trait Anxiety InventoryBaseline, post conditioning up to 6 minutesThe Spielberger State-Trait Anxiety Inventory (STAI) is a 40-item self-report questionnaire with 20 items designed to assess State anxiety (temporary feelings of anxiety). The State anxiety score range is between 20 and 80 with higher scores representing higher anxiety. State anxiety was measured and is reported.
Experimental Pain as Assessed by a Pain Rating ScalePost conditioning approximately 6 minutesPain Rating for Unpleasantness on a scale of 0 - 10 where 10 is the worst imaginable. All participants experienced two types of conditioned stimuli, one stimulus signaled danger and the other safety. Only during the danger stimulus would the participant receive a laser pulse.

Countries

United States

Participant flow

Pre-assignment details

A total of 32 participants were consented. 1 participant didn't meet criteria and was not randomized.

Participants by arm

ArmCount
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.
Skin conductance levels and slopes over time in conditioned fear as metrics.as metrics for anxiety: After fear conditioning the cue induces autonomic responses like skin conductance and cognitive ratings like expectancy of the unconditioned stimulus after cueing or conditioning. Activity across blocks in the conditioning stage shows that the skin conductance can be described by levels, and slopes which might be related to state anxiety and trait anxiety (Spielberger trait and state anxiety inventory or questionnaire). These skin conductance measures may be concrete metrics for psychological processes in healthy subjects. We will carry out a partial correlation analysis of levels, state anxiety and trait anxiety, and then a similar analysis of slopes, state anxiety and trait anxiety. These results may show that concrete skin conductance levels and slopes are related to metrics of subjective self report measures of state and trait anxiety.
31
Total31

Baseline characteristics

CharacteristicEye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.
Age, Continuous26.8 years
STANDARD_DEVIATION 13.2
Ethnicity (NIH/OMB)
Hispanic or Latino
2 Participants
Ethnicity (NIH/OMB)
Not Hispanic or Latino
29 Participants
Ethnicity (NIH/OMB)
Unknown or Not Reported
0 Participants
Race (NIH/OMB)
American Indian or Alaska Native
0 Participants
Race (NIH/OMB)
Asian
9 Participants
Race (NIH/OMB)
Black or African American
2 Participants
Race (NIH/OMB)
More than one race
2 Participants
Race (NIH/OMB)
Native Hawaiian or Other Pacific Islander
0 Participants
Race (NIH/OMB)
Unknown or Not Reported
1 Participants
Race (NIH/OMB)
White
17 Participants
Sex: Female, Male
Female
14 Participants
Sex: Female, Male
Male
17 Participants

Adverse events

Event typeEG000
affected / at risk
deaths
Total, all-cause mortality
0 / 31
other
Total, other adverse events
1 / 31
serious
Total, serious adverse events
0 / 31

Outcome results

Primary

Experimental Pain as Assessed by a Pain Rating Scale

Pain Rating for Unpleasantness on a scale of 0 - 10 where 10 is the worst imaginable. All participants experienced two types of conditioned stimuli, one stimulus signaled danger and the other safety. Only during the danger stimulus would the participant receive a laser pulse.

Time frame: Post conditioning approximately 6 minutes

ArmMeasureGroupValue (MEAN)Dispersion
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.Experimental Pain as Assessed by a Pain Rating ScaleDanger Stimulus3.43 score on a scaleStandard Error 0.59
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.Experimental Pain as Assessed by a Pain Rating ScaleSafety Stimulus.82 score on a scaleStandard Error 0.27
Primary

Skin Conductance Response

Concrete metric is skin conductance response to painful laser pulse stimulus measured in microSiemens. Higher values mean more emotional arousal or stress. All participants experienced two types of conditioned stimuli, one stimulus signaled danger and the other safety. Only during the danger stimulus would the participant receive a laser pulse.

Time frame: 5 seconds post conditioned stimulus

ArmMeasureGroupValue (MEAN)Dispersion
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.Skin Conductance ResponseDanger Stimulus.19 micro SiemensStandard Error 0.037
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.Skin Conductance ResponseSafety Stimulus.016 micro SiemensStandard Error 0.0068
Primary

State Anxiety as Assessed by the Spielberger State-Trait Anxiety Inventory

The Spielberger State-Trait Anxiety Inventory (STAI) is a 40-item self-report questionnaire with 20 items designed to assess State anxiety (temporary feelings of anxiety). The State anxiety score range is between 20 and 80 with higher scores representing higher anxiety. State anxiety was measured and is reported.

Time frame: Baseline, post conditioning up to 6 minutes

ArmMeasureGroupValue (MEAN)Dispersion
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.State Anxiety as Assessed by the Spielberger State-Trait Anxiety InventoryBaseline36.28 score on a scaleStandard Error 1.56
Eye Position and Tense Arousal Over Time a Metrics for Sustained Attention in Conditioned Fear.State Anxiety as Assessed by the Spielberger State-Trait Anxiety InventoryPost Conditioning39.59 score on a scaleStandard Error 2.22

Source: ClinicalTrials.gov · Data processed: Feb 4, 2026