Intra- and Inter-individual Differences of Pain

NCT05616091 | Completed

• 1 other identifier: 11/2019
• Study Type: interventional
• Target: 162
• Locations: 1 country
• Sites: 1

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.

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

Outcome Measures

Primary Outcomes (2)

• Verbal pain rating (NRS; 0: 'no pain' to 100: 'maximal tolerable pain')

  Eighty painful stimuli will be applied to the participants' left hand. Participants will be instructed to verbally rate the perceived pain intensity of each stimulus on a numerical rating scale (see above).

  During procedure (15 min experimental paradigm in each session)

• Pain-associated brain responses

  A 64-channel electroencephalogram (EEG) will be recorded. In offline analyses, Laser-evoked potentials (LEPs) will be quantified with regard to amplitudes and latencies. In addition, power of oscillatory brain activity will be quantified in the alpha (8-13 Hz), beta (14-30 Hz) and gamma (30-100 Hz) frequency bands.

  During procedure (15 min experimental paradigm in each session)

Secondary Outcomes (6)

• skin conductance response (µS)

  During procedure (15 min experimental paradigm in each session)

• Customized protocol

  At the beginning of each session

• German version of the Pittsburgh Sleep Quality Index (PSQI)

  At the beginning of each session

• German version of the Hospital Anxiety and Depression Scale (HADS)

  At the beginning of each session

• German version of the Positive and Negative Affect Scale (PANAS)

  At the beginning of each session

Interventions

painful stimulation by using a laser device (DEKA Stimul 1340, Calenzano, Italy) DEVICE

In each of the two sessions, 80 experimental painful stimuli of different intensities (2.5 J, 3 J, 3.5 J, 4 J) will be applied using the laser device listed above.

Eligibility Criteria

• Age: 18 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)

You may qualify if:

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

You may not qualify if:

• 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

Sponsors & Collaborators

• Technical University of Munich: lead
• German Research Foundation: collaborator

Study Sites (1)

Department of Neurology, Klinikum rechts der Isar, Technical University of Munich

Munich, Bavaria, 81675, Germany

Location

Related Publications (1)

• May ES, Tiemann L, Gil Avila C, Bott FS, Hohn VD, Gross J, Ploner M. Assessing the predictive value of peak alpha frequency for the sensitivity to pain. Pain. 2025 Mar 11;166(9):2076-2090. doi: 10.1097/j.pain.0000000000003571.

  PMID: 40085759 DERIVED

MeSH Terms

Conditions

Pain

Condition Hierarchy (Ancestors)

Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Markus Ploner, Prof. Dr. med.

  Department of Neurology, Klinikum rechts der Isar, Technische Universität München

  PRINCIPAL INVESTIGATOR

Study Design

• Study Type: interventional
• Phase: not applicable
• Allocation: NA
• Masking: SINGLE
• Who Masked: PARTICIPANT
• Masking Details: Participants will not be informed about the intensities of the nociceptive stimuli administered during the experimental paradigm.
• Purpose: BASIC SCIENCE
• Intervention Model: SINGLE GROUP
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Professor of Human Pain Research

Model Details: 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).

Study Record Dates

• First Submitted: November 7, 2022
• First Posted: November 15, 2022
• Study Start: December 10, 2019
• Primary Completion: December 15, 2022
• Study Completion: December 15, 2022
• Last Updated: January 25, 2023

Record last verified: 2023-01

Data Sharing

• IPD Sharing: Will share

Locations

DE (1)