Interaction Between NGF and Acute Exercise-induced Ischemia

The Interaction Between NGF-induced Muscle Sensitivity and Acute Exercise-induced Ischemia

The purpose of this study is to investigate pain evoked responses and facilitation of NGF-induced mechanical muscle hyperalgesia over time following an acute exercised-induced ischemic condition in a NGF-sensitized muscle.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Hyperalgesia; Pain Response
• Intervention / Treatment: Drug: NGF; Drug: Isotonic saline

Detailed Description

Assessing evoked pain responses and muscle hyperalgesia following contractions during acute ischemia in a NGF-sensitized muscle may clarify whether an interaction between NGF sensitization and acidic stimulation exist.

It is hypothesized that acute ischemic exercise with the NGF-sensitized TA muscle, in contrast to ischemic exercise in a non-sensitized would: 1) potentiate pain-evoked responses, and 2) facilitate NGF-induced muscle hyperalgesia.

• Study Type: Interventional
• Enrollment (Actual): 21
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9220
    • Aalborg University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 16 years to 53 years (Adult)
• Accepts Healthy Volunteers: No
• Genders Eligible for Study: All

Description

Inclusion Criteria:

• Healthy and pain free volunteers

Exclusion Criteria:

• Pregnancy
• Drug addiction defined as the use of cannabis, opioids or other drugs
• Previous neurologic, mental illnesses, or psychiatric diseases.
• Past history of chronic pain in the musculoskeletal system (muscle, joint, cartilage, connective tissue)
• Participation in other pain trials throughout the study period
• Lack of ability to cooperate
• Taking any analgesic 24 hours before the injections
• Performing any strenuous leg exercise through out the study period causing sore muscles

Study Plan

How is the study designed?

Design Details

• Primary Purpose: Basic Science
• Allocation: Randomized
• Interventional Model: Crossover Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: NGF condition + Control condition; All participants will receive five injections with NGF (1ug/0.5ml) into the tibialis anterior muscle in their non-dominant leg After 4 weeks: All participants will receive five injections with isotonic saline (9%/0.5ml) into the tibialis anterior muscle in their non-dominant leg	Drug: NGF; Intramuscular injection; Other Names: Beta-Nerve Growth Factor, Human; Drug: Isotonic saline; Intramuscular injection; Other Names: Control
Experimental: Control condition + NGF condition; All participants will receive five injections with isotonic saline (9%/0.5ml) into the tibialis anterior muscle in their non-dominant leg After 4 weeks: All participants will receive five injections with NGF (1ug/0.5ml) into the tibialis anterior muscle in their non-dominant leg	Drug: NGF; Intramuscular injection; Other Names: Beta-Nerve Growth Factor, Human; Drug: Isotonic saline; Intramuscular injection; Other Names: Control

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle sensitivity	Pressure pain thresholds (PPTs) are assessed over the non-dominant tibialis anterior muscle using a handhold pressure algometer.	Change from baseline at 1 week

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Ischemic-induced pain intensity	Subjects perform 45 dorsiflexions with their non-dominant leg while a cuff is mounted over the knee to occlude the blodflow from the muscle (ischemia) Subjects subsequently rate their perceived pain intensity verbally on a numeric rating scale (NRS)	Assessed right after the dorsiflexions have been performed
Functional muscle pain	Subjects evaluate their muscle pain during movement using a Likert Scale for lower limp	Change from baseline at 1 week
Muscle pain diary	Subjects evaluate their muscle pain during movement using a Likert Scale for lower limp and perceived pain intensity at rest on a numeric rating scale (NRS). The diary is filled out at home on days between sessions	Change from baseline at 1 week

Collaborators and Investigators

• Sponsor: Aalborg University
• Investigators: Principal Investigator: Line Bay Sørensen, Ph.d stud., Aalborg University

Publications and helpful links

General Publications

• Sorensen LB, Gazerani P, Graven-Nielsen T. Nerve growth factor-induced muscle hyperalgesia facilitates ischaemic contraction-evoked pain. Eur J Pain. 2019 Nov;23(10):1814-1825. doi: 10.1002/ejp.1455. Epub 2019 Aug 5. Erratum In: Eur J Pain. 2020 Feb;24(2):470-472.

Study record dates

Study Major Dates

• Study Start (Actual): March 15, 2018
• Primary Completion (Actual): May 15, 2018
• Study Completion (Actual): June 15, 2018

Study Registration Dates

• First Submitted: March 13, 2018
• First Submitted That Met QC Criteria: March 13, 2018
• First Posted (Actual): March 19, 2018

Study Record Updates

• Last Update Posted (Actual): February 15, 2019
• Last Update Submitted That Met QC Criteria: February 14, 2019
• Last Verified: February 1, 2019

More Information

Terms related to this study

• Keywords: Hyperalgesia; NGF pain model; NGF-induced pain; Ischemia-induced pain
• Additional Relevant MeSH Terms: Pathologic Processes; Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Ischemia; Hyperalgesia; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: N-2017-0007_S2

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