Influence of Pain on Exercise-induced Hypoalgesia

The Influence of Pain on Exercise-Induced Hypoalgesia in Healthy Subjects: A Randomized Controlled Trial

The purpose of this study is to investigate how acute pain induced by hypertonic saline prior to exercise influence the magnitude of exercise-induced hypoalgesia after a 3 min isometric wallsquat exercise in healthy subjects. The study is a single blinded (investigator) randomized cross-over trial The results from the study may be of great importance to the understanding of exercise-induced hypoalgesia, and whether the presence of pain affects the effects of exercise.

Study Overview

• Status: Completed
• Conditions: Pain
• Intervention / Treatment: Behavioral: Pain (hypertonic saline); Behavioral: No pain (Hypotonic saline)

Detailed Description

Exercise is recommended to promote and maintain health and as treatment for more than 25 chronic diseases and pain conditions.

The mechanisms underlying pain relief of exercise are largely unknown but may be related to the modulation of central descending pain inhibitory pathways after acute exercise bouts. Exercise-induced hypoalgesia (EIH) is typically assessed as the temporary change in PPTs after a short acute exercise bout and EIH is seen as a proxy of descending pain inhibitory control. In general, EIH seems hypoalgesic (functional) in asymptomatic subjects. A hyperalgesic (impaired) EIH response has been reported in different chronic pain populations, although a functional EIH response also has been reported in subgroups of knee osteoarthritis patients. This implies differences in the acute response to exercise between healthy (pain-free) subjects and chronic pain patients, but it is still unknown whether the presence of pain itself affects the pain alleviating response (i.e. the EIH response) to acute exercise.

It is hypothesized that acute pain will decrease the EIH response magnitude following hypertonic saline injection compared with the control injection. This study will increase the insight into the EIH mechanisms in healthy subjects in general, and how the presence of pain affects the body's own ability to modulate pain during exercise.

• Study Type: Interventional
• Enrollment (Actual): 35
• Phase: Not Applicable

Contacts and Locations

Study Locations

• Denmark
  • Funen
    • Odense, Funen, Denmark, 5000
      • Pain Center, University Hospital Odense

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 50 years (ADULT)
• Accepts Healthy Volunteers: Yes
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Pain-free
• Understands and writes Danish

Exclusion Criteria:

• Pregnancy
• Previous addictive behavior defined as abuse of hash, opioids or other euphoric substances.
• Previous painful or mental illnesses, neurological or circulatory diseases in the form of heart or lung disease.
• Surgery within last 3 months
• Pain on the days of testing
• Pain for more than 2 weeks within the last 3 months

Study Plan

How is the study designed?

Design Details

• Primary Purpose: BASIC_SCIENCE
• Allocation: RANDOMIZED
• Interventional Model: CROSSOVER
• Masking: SINGLE

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
EXPERIMENTAL: Pain (hypertonic saline); Injection (1 ml) of painful hypertonic saline (5.8%) prior to performance of the 3 min wall squat exercise	Behavioral: Pain (hypertonic saline); A bolus injection (1 ml) of hypertonic saline (5.8%) is injected into the right quadriceps femoris of the quadriceps femoris muscle 1 minute before performance of the 3 min wall squat exercise
PLACEBO_COMPARATOR: No pain (Hypotonic saline); Injection (1 ml) of non-painful isotonic saline (0.9%) prior to performance of the 3 min wall squat exercise	Behavioral: No pain (Hypotonic saline); A bolus injection (1 ml) of isotonic saline (0.9%) is injected into the right quadriceps femoris of the quadriceps femoris muscle 1 minute before performance of the 3 min wall squat exercise

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure pain threshold at the right quadriceps muscle where injection is performed.	Between group comparison of the primary outcome, which is change in pressure pain threshold at the right quadriceps muscle from before wall squat to after wall squat. Pressure pain threshold is measured with a hand held pressure algometer.	Before and after the 3 minutes wall squat

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure pain threshold at the non-dominant trapezius muscle	Between group comparison of the secondary outcome, which is change in pressure pain threshold at the left trapezius muscle from before wall squat to after wall squat. Pressure pain threshold is measured with a hand held pressure algometer.	Before and after the 3 minutes wall squat
Pressure pain threshold at the left quadriceps muscle where injection is not performed.	Between group comparison of the secondary outcome, which is change in pressure pain threshold at the left quadriceps muscle from before wall squat to after wall squat. Pressure pain threshold is measured with a hand held pressure algometer.	Before and after the 3 minutes wall squat
Pain Intensity in thighs	Pain intensity in both thighs are assessed with numerical rating scales with 0 = no pain and 10 = maximal pain.	Assessed before and immediately after hypertonic and isotonic saline injection as well as after 1, 2 and 3 min of wall squat, and immediately after the end of wall squat

Other Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure pain threshold	Cuff pressure pain threshold (cPPT) is assessed using a computer-controlled cuff pressure algometer (CPAR, NociTech, Denmark,). A 13-cm wide silicone tourniquet cuff is wrapped around the right lower leg with an 8-cm distance to the tibial tuberosity. The cuff pressure is increased with a rate of 1 kPa/s and the maximal pressure limit is 100 kPa. The participants use an electronic visual analog scale (VAS) to rate the pressure-induced pain intensity and a button to release the pressure. Zero- and 10-cm extremes on the VAS were defined as "no pain" and as "maximal pain," respectively. The participants are instructed to rate the pain intensity continuously on the electronic VAS from when the pressure was defined as first sensation of pain and to press the pressure release button when the pain was intolerable. The pressure value when the subject rated the sensation of pain as 1 cm on the VAS was defined as the cPPT.	At baseline on both days before saline injections
Pressure pain tolerance	Cuff pressure pain tolerance (cPTT) is assessed using a computer-controlled cuff pressure algometer (CPAR, NociTech, Denmark,). A 13-cm wide silicone tourniquet cuff is wrapped around the right lower leg with an 8-cm distance to the tibial tuberosity. The cuff pressure is increased with a rate of 1 kPa/s and the maximal pressure limit is 100 kPa. The participants use an electronic visual analog scale (VAS) to rate the pressure-induced pain intensity and a button to release the pressure. Zero- and 10-cm extremes on the VAS were defined as "no pain" and as "maximal pain," respectively. The participants are instructed to rate the pain intensity continuously on the electronic VAS from when the pressure was defined as first sensation of pain and to press the pressure release button when the pain was intolerable. The pressure value when the subject terminates the pressure inflation is defined as the cPTT.	At baseline on both days before saline injections
Temporal summation of pain	Temporal summation of pain (TSP) is assessed at the right lower leg with computer-controlled cuff algometry. Ten repeated cuff pressure stimulations lasting 1 second each (1 sec breaks in between) are induced to assess TSP. Stimulations are delivered by rapid inflation of the cuff with an intensity equivalent to the pressure pain tolerance. Subjects rate the pain intensity on an electronic VAS continuously during the sequential stimulation without returning the VAS to zero between stimulations. VAS scores immediately after each stimulus are extracted, and TSP is calculated as the ratio of the last 3 stimulations to the first four stimulations, with positive values indicating an increase in pain intensity ratings during the repeated stimulation.	At baseline on both days before saline injections
International Physical Activity Questionnaire (IPAQ)	The IPAQ is suitable for adults between 15 and 69 years of age and is used for sample surveillance of physical activity levels.	Baseline of first session

Collaborators and Investigators

• Sponsor: Odense University Hospital
• Collaborators: Aalborg University

Publications and helpful links

General Publications

• Hansen S, Petersen KK, Sloth E, Manum LA, McDonald AK, Andersen PG, Vaegter HB. Hypoalgesia after exercises with painful vs. non-painful muscles in healthy subjects - a randomized cross-over study. Scand J Pain. 2021 Dec 27;22(3):614-621. doi: 10.1515/sjpain-2021-0161. Print 2022 Jul 26.

Study record dates

Study Major Dates

• Study Start (ACTUAL): June 19, 2020
• Primary Completion (ACTUAL): September 14, 2020
• Study Completion (ACTUAL): September 14, 2020

Study Registration Dates

• First Submitted: April 17, 2020
• First Submitted That Met QC Criteria: April 17, 2020
• First Posted (ACTUAL): April 21, 2020

Study Record Updates

• Last Update Posted (ACTUAL): September 22, 2020
• Last Update Submitted That Met QC Criteria: September 21, 2020
• Last Verified: September 1, 2020

More Information

Terms related to this study

• Keywords: hypertonic saline; Pressure pain threshold; Exercise-induced hypoalgesia
• Other Study ID Numbers: S-20190081

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