Exercise-induced Ischemia and the Influence of Pain Modulation in a Nerve Growth Factor (NGF) Model

Early Phase 1

• Conditions: Pain Response; Hyperalgesia; Healthy Subjects
• Interventions: Drug: NGF; Drug: Isotonic-saline

• Registration Number: NCT03844243
• Lead Sponsor: Aalborg University

Brief Summary

The purpose of this study is to investigate responses of pain and the maintenance of mechanical muscle hypersensitivity following an acute exercise-induced ischemic condition repeated over time in a prolonged NGF-sensitized muscle. Additionally, the influence of the pain modulating system on prolonged NGF muscle hypersensitivity caused by peripheral mechanisms and central mechanisms will also be investigated.

Detailed Description

The hypothesis is that an ischemic conditioning in a NGF-sensitized muscle is able to facilitate pain responses and that over time the pain modulation system is responsible for a subsequent reduction in muscle sensitivity towards mechanical pressure and a decrease in pain intensity following a period of NGF-induced muscle hypersensitivity.

Study Timeline

• Status Verified: 2019-02
• Study First Submitted: 2019-02-14
• Study First Submitted QC: 2019-02-15
• Last Update Submitted: 2019-02-15
• Study Start: 2019-02-18
• Study First Posted: 2019-02-18
• Last Update Posted: 2019-02-18
• Primary Completion: 2019-06-30
• Study Completion: 2019-06-30

Recruitment & Eligibility

• Status: UNKNOWN
• Sex: All
• Target Recruitment: 20

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 & Design

• Study Type: INTERVENTIONAL
• Study Design: CROSSOVER

Arm && Interventions

Group	Intervention	Description
NGF condition + Control condition	NGF	All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle.
NGF condition + Control condition	Isotonic-saline	All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle.
Control condition + NGF condition	Isotonic-saline	All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle.
Control condition + NGF condition	NGF	All participants will receive 3 single injection of isotonic-saline (9%/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle. After 4 weeks: All participants will receive 3 single injection of NGF (1ug/0.5ml) repeated over 3 separate days in their dominant tibialis anterior muscle.

Primary Outcome Measures

Name	Time	Method
Muscle pain sensitivity (PPTs values) assessed by pressure algometer	Change from baseline at 3 week	Pressure pain thresholds (PPTs) are assessed over the dominant tibialis anterior muscle using a handhold pressure algometer.

Secondary Outcome Measures

Name	Time	Method
Functional muscle pain	Change from baseline at 3 weeks	Subjects evaluate their muscle pain during movement using a 7-point Likert Scale for lower limp rating from 0 (a complete absence of pain) to 6 (a severe pain that limits my ability to move).
Conditioning pain modulation (CPM) efficacy	Change from baseline at 3 weeks	A test stimuli will be applied and compared with a test stimuli simultaneous a condition stimuli.
Ischemic-induced pain intensity	Assessed right after the exercise has been performed, change from baseline at 3 weeks	Subjects perform a repeated static exercise with their 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 11-point numeric rating scale (NRS) rating from 0 (no pain) to 10 (worst pain imaginable).
Temporal summation of pain	Change from baseline at 3 weeks	10 repeated stimuli will be applied and subjects will be asked to rate the pain for each individual stimuli on a 11-point visual analogue scale (VAS) rating from 0 (no pain) to 10 (worst pain imaginable)

Trial Locations

Locations (1)

Aalborg University; 🇩🇰 Aalborg, Denmark