The Effect of Capsaicin-induced Pain on Homeostatic Plasticity in Healthy Human Participants

People suffering from chronic pain exhibit changes in the way the central nervous system processes pain. Some of the changes in the central nervous system are associated with how the brain adapts to the process of different stimuli. There are several physiological mechanisms that regulates how the brain adapts to changes and one of these mechanisms is called homeostatic plasticity (or equilibrium plasticity ). In healthy participants homeostatic plasticity mechanisms have been tested and considered normal, whereas in patients with chronic conditions, such as low back pain, this mechanism was shown to be dysfunctional. However, it is unknown when this difference in the pain system develops. It is possible that homeostatic mechanism becomes impaired during early stages of pain. This experiment will investigate the effect of capsaicin-induced pain on homeostatic plasticity in healthy participants.

Study Overview

• Status: Unknown
• Conditions: Healthy
• Intervention / Treatment: Drug: Capsaicin Topical - alone; Drug: Placebo - alone; Drug: Capsaicin Topical - ice; Drug: Placebo - ice

Detailed Description

The aim of this study is to investigate the effect of capsaicin-induced pain on homeostatic plasticity.

A randomised crossover design will be used to evaluate the effect of capsaicin-induced pain on homeostatic plasticity using cathodal transcranial direct current stimulation (tDCS). Each participant will take part in four experimental sessions during which homeostatic plasticity and corticomotor excitability will be induced and measured in the left primary motor cortex. Participants will receive - in randomised order - capsaicin or placebo patch placed on the dorsal part of the right hand.

Each participant will attend four sessions, being two consecutive sessions separated by two weeks (i.e. wash-out period). During the experiment, participants will be seated comfortably with hands and arms at rest. First, the electromyography electrodes will be placed at the right first dorsal interosseous muscle to be used for assessing the corticomotor excitability by recordings of motor evoked potentials by transcranial magnetic stimulation (TMS) on the left primary motor cortex. Then, the cap for tDCS on the left primary motor cortex will be mounted. The optimal scalp position (hot spot) for TMS stimulation will be identified and marked with a pen on the cap for standardisation. A 5 x 7 cm capsaicin/placebo patch will be placed on participants' right hand. After 30 minutes of patch application, baseline measures of pain and motor-evoked potentials will be taken. Then, the homeostatic plasticity induction process will take place followed by motor-evoked potentials recordings every 15 minutes up to 45 minutes post protocol. Participants will be divided in 2 groups, one group will receive ice over the patch as to reduce pain intensity to minimum of 1 in a numeric rating scale; the other group will proceed without ice. Homeostatic plasticity will be induced and measured as previously described. The patch will be left in place for 24 hours, at which point participants will return to the laboratory and homeostatic plasticity will once again be induced and measured. After a wash-out period of two weeks, participants will go through an identical process but at this time with a different patch.

Homeostatic plasticity will be induced in the left primary motor cortex using tDCS applied for 7 minutes followed by an interval of 3 minutes and another block of 5 minutes of stimulation. A constant current of 2mA will be transmitted through the tDCS system, using two 25 cm2 electrodes placed into holes of a cap over the hot spot and right supraorbital area.

A sample size calculation was conducted using α of 0.05, β of 0.80 and effect size of 0.29 based on motor evoked potential (MEP) analysis of previous studies resulting in a target of 22 participants. To account for differences in designs 24 participants will be included, being 12 in each group.

Data distribution will be assessed using the Shapiro-Wilk test. A mixed analysis of variance (ANOVA) will be conducted on mean MEPs: within factors Intervention (Capsaicin and Placebo), Time (baseline, 0 min, 15 min, min, 30 min, 45 min), Time with pain (immediate, post pain relief post prolonged pain); and between factor (ice , no ice). A Greenhouse-Geisser correction will be used if Mauchly's test shows that sphericity cannot be assumed. Adjustments will be made for multiple post-hoc comparisons using the Bonferroni correction. Results will be interpreted according to the level of statistical significance p≤0.05.

• Study Type: Interventional
• Enrollment (Anticipated): 24
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9220
    • Recruiting
    • Aalborg University
    • Contact: Priscilla G Wittkopf, PhD; Phone Number: +4531539979; Email: pgw@hst.aau.dk

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 60 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy, aged between 18-60 years, right-handed and can speak and understand English.

Exclusion Criteria:

• Lack of ability to cooperate
• Chili allergy
• History or present chronic pain or current acute pain
• Pregnancy
• Drug addiction defined as the use of cannabis, opioids or other drugs
• Present and previous neurological disorders such as epilepsy, Alzheimer's disease,
• dementia, stroke, migraine and other headache disorders, multiple sclerosis,
• Parkinson's disease, neuroinfections, brain tumors and head trauma.
• Present or previous musculoskeletal disorders such as tendonitis, degenerative disc disease, mechanical back syndrome, and ruptured/herniated disc.
• Present or previous mental illnesses such as depression, bipolar disorder, and schizophrenia.
• Current use of medications that may affect the trial (e.g. analgesics, anti- inflammatories, anti-depressives)
• Contraindications to TMS application (history of epilepsy, metal implants in head or jaw, etc.)
• Failure to pass the tDCS screening questionnaire
• Failure to pass the "TASS questionnaire"

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Non-Randomized
• Interventional Model: Parallel Assignment
• Masking: Single

Number of Arms

4

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Capsaicin - alone; 5x7 cm2 capsaicin patch	Drug: Capsaicin Topical - alone; 5x7 cm2 capsaicin patch applied on the dorsal area of the hand and left in place for 24 hours
Placebo Comparator: Placebo - alone; 5x7 cm2 placebo patch alone	Drug: Placebo - alone; 5x7 cm2 patch applied on the dorsal area of the hand and left in place for 24 hours
Experimental: Capsaicin - ice; 5x7 cm2 capsaicin patch - plus ice	Drug: Capsaicin Topical - ice; 5x7 cm2 capsaicin patch applied on the dorsal area of the hand and left in place for 24 hours. Ice will be applied on top of the patch 1.5 hrs post patch application and left in place for 1 hr.
Placebo Comparator: Placebo - ice; 5x7 cm2 placebo patch - plus ice	Drug: Placebo - ice; 5x7 cm2 patch applied on the dorsal area of the hand and left in place for 24 hours. Ice will be applied on top of the patch 1.5 hrs post patch application and left in place for 1 hr.

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Conspiratorial excitability	Corticospinal excitability measured as motor evoked potentials amplitude induced by transcranial magnetic stimulation.	[Time Frame: 0 minutes post homeostatic plasticity induction]
Conspiratorial excitability	Corticospinal excitability measured as motor evoked potentials amplitude induced by transcranial magnetic stimulation.	[Time Frame: 15 minutes post homeostatic plasticity induction]
Conspiratorial excitability	Corticospinal excitability measured as motor evoked potentials amplitude induced by transcranial magnetic stimulation.	[Time Frame: 30 minutes post homeostatic plasticity induction]
Conspiratorial excitability	Corticospinal excitability measured as motor evoked potentials amplitude induced by transcranial magnetic stimulation.	[Time Frame: 45 minutes post homeostatic plasticity induction]

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pain intensity	Pain intensity measured using an 11-point numeric rating scale where 0= no pain and 10 = worst imaginable pain.	Every 10 minutes post capsaicin application

Collaborators and Investigators

• Sponsor: Aalborg University

Publications and helpful links

General Publications

• Rossini PM, Burke D, Chen R, Cohen LG, Daskalakis Z, Di Iorio R, Di Lazzaro V, Ferreri F, Fitzgerald PB, George MS, Hallett M, Lefaucheur JP, Langguth B, Matsumoto H, Miniussi C, Nitsche MA, Pascual-Leone A, Paulus W, Rossi S, Rothwell JC, Siebner HR, Ugawa Y, Walsh V, Ziemann U. Non-invasive electrical and magnetic stimulation of the brain, spinal cord, roots and peripheral nerves: Basic principles and procedures for routine clinical and research application. An updated report from an I.F.C.N. Committee. Clin Neurophysiol. 2015 Jun;126(6):1071-1107. doi: 10.1016/j.clinph.2015.02.001. Epub 2015 Feb 10.
• Fricke K, Seeber AA, Thirugnanasambandam N, Paulus W, Nitsche MA, Rothwell JC. Time course of the induction of homeostatic plasticity generated by repeated transcranial direct current stimulation of the human motor cortex. J Neurophysiol. 2011 Mar;105(3):1141-9. doi: 10.1152/jn.00608.2009. Epub 2010 Dec 22.
• Thapa T, Graven-Nielsen T, Chipchase LS, Schabrun SM. Disruption of cortical synaptic homeostasis in individuals with chronic low back pain. Clin Neurophysiol. 2018 May;129(5):1090-1096. doi: 10.1016/j.clinph.2018.01.060. Epub 2018 Feb 9.
• Thapa T, Schabrun SM. Test-Retest Reliability of Homeostatic Plasticity in the Human Primary Motor Cortex. Neural Plast. 2018 Jun 10;2018:6207508. doi: 10.1155/2018/6207508. eCollection 2018.
• Karabanov A, Ziemann U, Hamada M, George MS, Quartarone A, Classen J, Massimini M, Rothwell J, Siebner HR. Consensus Paper: Probing Homeostatic Plasticity of Human Cortex With Non-invasive Transcranial Brain Stimulation. Brain Stimul. 2015 May-Jun;8(3):442-54. doi: 10.1016/j.brs.2015.01.404. Epub 2015 Apr 1.

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2020
• Primary Completion (Anticipated): December 1, 2020
• Study Completion (Anticipated): December 1, 2020

Study Registration Dates

• First Submitted: July 13, 2020
• First Submitted That Met QC Criteria: July 23, 2020
• First Posted (Actual): July 24, 2020

Study Record Updates

• Last Update Posted (Actual): August 31, 2020
• Last Update Submitted That Met QC Criteria: August 28, 2020
• Last Verified: August 1, 2020

More Information

Terms related to this study

• Additional Relevant MeSH Terms: Physiological Effects of Drugs; Peripheral Nervous System Agents; Sensory System Agents; Dermatologic Agents; Antipruritics; Capsaicin
• Other Study ID Numbers: N-20190069/2

Plan for Individual participant data (IPD)

• Plan to Share Individual Participant Data (IPD)?: No

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No