Spread of Muscle Hyperalgesia and Pain in a Low Dose NGF-induced Pain Model

The purpose of this study is to investigate and determine the time course and distribution on muscle hyperalgesia and muscle pain in a repeated, low dose NGF model. It is hypothesized that low dosages i.m injections of NGF are able to induce mechanical hyperalgesia and muscle soreness in a same manner (effect of duration) as for dosages previously used in NGF studies. Furthermore, it is also speculated if several injections of low dose NGF into the muscle combined are able to course immediate pain sensation and spreading of muscle hypersensitivity.

Study Overview

• Status: Completed
• Conditions: Healthy Subjects; Hyperalgesia
• Intervention / Treatment: Drug: NGF

Detailed Description

Effects of pain responses, symptom development and pattern (time course and distribution) following 5 i.m low dose injections of NGF injected into the tibialis anterior muscle will be compared to a high dose i.m injection of NGF injected into the contralateral side in healthy pain-free subjects.

• Study Type: Interventional
• Enrollment (Actual): 20
• Phase: Early Phase 1

Contacts and Locations

Study Locations

• Denmark
  • Aalborg, Denmark, 9220
    • Aalborg University

Participation Criteria

Eligibility Criteria

• Ages Eligible for Study: 18 years to 55 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: Single Group Assignment
• Masking: Double

Number of Arms

2

Arms and Interventions

Participant Group / Arm	Intervention / Treatment
Experimental: Low dose; All participants will receive 5 i.m injections of NGF (1 ug/0.5ml) into the tibialis anterior muscle (either left or right leg)	Drug: NGF; Intramuscular injection; Other Names: Beta-Nerve Growth Factor, Human
Experimental: High dose; All participants will receive 1 high dose i.m bolus injection of NGF (5 ug/0.5ml) and 4 injections of saline (control/same volume) into the tibialis anterior muscle (either left or right leg)	Drug: NGF; Intramuscular injection; Other Names: Beta-Nerve Growth Factor, Human

What is the study measuring?

Primary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Muscle sensitivity	Pressure pain thresholds (PPTs) are assessed over the tibialis anterior muscles using a handhold pressure algometer.	Change from baseline at 3 weeks

Secondary Outcome Measures

Outcome Measure	Measure Description	Time Frame
Pressure-induced referred pain	At three predetermined sites within the tibialis anterior muscle, a constant pressure stimulation (120% of PPT) is evoked by use of the pressure algometer. Subjects color their perceived sensation of pain on an electronic schematic of the lower legs using Navigate Pain.	Change from baseline at 3 weeks
Activity-induced muscle soreness	Subjects perform 10 dorsiflexions with each leg. The perceived muscle soreness is reported using a numeric rating scale (NRS) and the area of soreness is colored on an electronic schematic of the lower legs (Navigate Pain).	Change from baseline at 3 weeks
Pain intensity	Subjects rate their perceived pain intensity on a visual analogue scale (VAS) App (Aalborg University) as displayed on a tablet computer with a sample rate of 1 Hz.	Assessed continuously at 0-5 min during the injections at each leg
Muscle soreness Diary	Two times a day subjects evaluate their muscle soreness using a Likert Scale of muscle soreness for lower limp	Change from baseline at 3 weeks
Activity-induced muscle soreness Diary	Subjects perform 10 dorsiflexions with each leg. The perceived muscle soreness is reported using a numeric rating scale (NRS) and the area of soreness is colored on an electronic schematic of the lower legs (Navigate Pain). The activity is performed at home on days in between the sessions	Change from baseline at 1 week

Collaborators and Investigators

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

Study record dates

Study Major Dates

• Study Start (Actual): July 1, 2017
• Primary Completion (Actual): October 1, 2017
• Study Completion (Actual): October 1, 2017

Study Registration Dates

• First Submitted: July 10, 2017
• First Submitted That Met QC Criteria: July 12, 2017
• First Posted (Actual): July 14, 2017

Study Record Updates

• Last Update Posted (Actual): January 11, 2018
• Last Update Submitted That Met QC Criteria: January 10, 2018
• Last Verified: January 1, 2018

More Information

Terms related to this study

• Keywords: Muscle soreness; NGF-induced pain; Pain model; Long-lasting sensitization
• Additional Relevant MeSH Terms: Nervous System Diseases; Neurologic Manifestations; Sensation Disorders; Somatosensory Disorders; Hyperalgesia; Molecular Mechanisms of Pharmacological Action; Mitosis Modulators; Mitogens
• Other Study ID Numbers: N-2017-0007

Drug and device information, study documents

• Studies a U.S. FDA-regulated drug product: No
• Studies a U.S. FDA-regulated device product: No
• product manufactured in and exported from the U.S.: No