Clinical trial NCT05616091: Intra- and Inter-individual Differences of Pain
Official title: Brain Mechanisms of Intra- and Inter-individual Differences in the Perception of Pain
Study type: INTERVENTIONAL
Overall status: COMPLETED
Phase: NA
Conditions: Experimental Pain in Healthy Human Subjects
Keywords: pain
variability
intra-individual
inter-individual
inter-session
electroencephalography
laser-evoked potentials
neuronal oscillations
alpha
gamma
brain
EEG
Lead sponsor: Technical University of Munich
Sponsor class: OTHER
Collaborators: name: German Research Foundation
First posted: 2022-11-15
Enrollment: 162
Sex: ALL
Minimum age (years): 18
Standard ages: ADULT
OLDER_ADULT
Accepts healthy volunteers: yes
Allocation: NA
Intervention model: SINGLE_GROUP
Intervention model description: Each participant will participate in two identical experimental sessions. Sessions will be separated from each other by one month. During each session, participants will undergo an experimental paradigm of about 15 min duration. In this paradigm, 80 experimental painful stimuli of different intensities will be applied using a laser device (DEKA Stimul 1340, Calenzano, Italy). Participants will be asked to verbally rate the intensity of every stimulus on a scale ranging from 0 ('no pain') to 100 ('maximally tolerable pain'). At the same time, brain responses will be recorded by using electroencephalography (EEG). Autonomic responses will be operationalized by the recording of skin conductance responses (SCRs).
Primary purpose: BASIC_SCIENCE

Brief summary: Pain is a highly subjective and variable phenomenon. Different persons perceive objectively identical nociceptive stimuli differently. Moreover, the same person may perceive objectively identical stimuli differently in different situations, or even from one moment to another. In the brain, the processing of pain is associated with different neuronal responses originating from an extended network of brain areas. These responses include evoked activity as well as neuronal oscillations at alpha (8-13 Hz), beta (14-30 Hz) and gamma (30-100 Hz) frequencies. All these responses covary with moment-to-moment variations of pain within subjects (intra-subject variability). However, only the gamma response correlates with variations of pain between subjects (inter-subject variability). To date, it has remained unknown whether these relationships remain stable and reproducible across longer periods of time (inter-session-variability). Thus, the current project aims to systematically characterize how different pain-associated brain responses encode intra-individual, inter-individual, and inter-session variations of pain perception. To this end, the investigators will record pain-associated brain responses of 155 healthy participants at two different points in time. Each time, short painful stimuli will be applied to the participants' hand and they will be asked to verbally rate the perceived pain intensity, while pain-associated brain responses will be recorded using electroencephalography (EEG). This will allow to investigate the relationships between pain-associated brain responses and intra-individual and inter-individual variations of pain and to compare these measures and their relationships between sessions. In order to quantify the influence of demographic and psychological factors, i.e. age, mood and sleep quality / quantity on pain variability, established questionnaires will be used. In order to compare the functional significance of brain responses to other pain-associated neuronal responses, pain-associated responses of the autonomic system will be recorded and related to pain variability. Results of the project promise to elucidate the neuronal mechanisms underlying intra-individual, inter-individual and inter-session variability of pain. Such knowledge provides the basis for the development of a biomarker for pain, which might reasonably complement the self-assessment of pain. Moreover, as pain perception and objective stimulation tend to dissociate in pathological pain, the current project promises insights into the neuronal mechanisms of chronic pain.


Eligibility criteria: Inclusion Criteria:

* aged 18 years or above
* Right-handedness
* Written informed consent

Exclusion Criteria:

* Pregnancy
* Neurological or psychiatric diseases (e.g. epilepsy, stroke, depression, anxiety disorders)
* Severe general illnesses (e.g. tumors, diabetes)
* Skin diseases (e.g. dermatitis, psoriasis or eczema)
* Current or recurrent pain
* (Regular) intake of centrally acting, antibiotic or analgesic medication
* Surgical procedures involving the brain or spinal cord
* Head trauma followed by impairment of consciousness
* Past fainting spells or syncopes
* Side-effects following previous electrical or magnetic stimulation
* Side-effects following previous thermal stimulation

Primary outcomes:
measure: Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximal tolerable pain')
timeFrame: During procedure (15 min experimental paradigm in each session)
measure: Pain-associated brain responses
timeFrame: During procedure (15 min experimental paradigm in each session)
Secondary outcomes:
measure: skin conductance response (µS)
timeFrame: During procedure (15 min experimental paradigm in each session)
measure: Customized protocol
timeFrame: At the beginning of each session
measure: German version of the Pittsburgh Sleep Quality Index (PSQI)
timeFrame: At the beginning of each session
measure: German version of the Hospital Anxiety and Depression Scale (HADS)
timeFrame: At the beginning of each session
measure: German version of the Positive and Negative Affect Scale (PANAS)
timeFrame: At the beginning of each session
measure: German version of the Pain Sensitivity Questionnaire (PSQ)
timeFrame: At the beginning of each session
Other outcomes:
Locations:
city: Munich
country: Germany
facility: Department of Neurology, Klinikum rechts der Isar, Technical University of Munich
state: Bavaria
Study officials:
affiliation: Department of Neurology, Klinikum rechts der Isar, Technische Universität München
name: Markus Ploner, Prof. Dr. med.
role: PRINCIPAL_INVESTIGATOR
References: