Investigating the Role of Central Pain Hypersensitivity in Skeletal Muscle Neural Drive

NCT07281651 | Recruiting

• 1 other identifier: FMHS 36-1124 / FMHS 128-0425
• Study Type: observational
• Target: 135
• Locations: 1 country
• Sites: 1

Brief Summary

Background: pain lasting for 12 weeks or beyond, which is often referred to as chronic pain, is common for people living with musculoskeletal conditions (e.g. arthritis, low back pain and fibromyalgia). Pain is often not directly related to the degree of muscle or joint damage. Adaptations of the central nervous system (brain, spinal cord and nerves) often occur in chronic musculoskeletal conditions and can influence how we feel pain (central pain hypersensitivity). Pain can impact on muscle activity and movement. Muscle activity is also governed by nerve signals from the central nervous system (neural drive). The goal of this cross-sectional observational study is to investigate whether chronic musculoskeletal pain is associated with altered nerve signalling (neural drive) to skeletal muscles in adults 40 years or over with chronic knee pain, fibromyalgia and healthy pain free volunteers. The main questions it aims to answer are:-

• Is central pain hypersensitivity associated with altered nerve signalling to skeletal muscles in adults 40 years or over with chronic pain (knee pain and for fibromyalgia) as well as healthy volunteers?
• Is altered nerve signalling to skeletal muscles associated with physical function and disability? Participants will be asked to:-
• Have sensory testing to determine how they feel pain
• Complete static leg and arm muscle contractions with electrodes on the skin to measure muscle electrical activity
• Complete questionnaires
• Perform a short set of mobility tasks including walking, rising from a chair and balancing.

Conditions

Chronic Knee Pain; Fibromyalgia

Keywords

Chronic Pain; Musculoskeletal Conditions; Fibromyalgia; Muscle Function; Physical Functioning; Disability; Central Aspects of Pain

Outcome Measures

Primary Outcomes (5)

• Pressure Pain Threshold

  Pressure Pain Threshold as an index of central pain hypersensitivity. Pressure Pain Threshold (PPT) performed with digital algometer, applied at proximal forearm. A gradually increasing pressure is applied, and participants indicate when the sensation of pressure turns to pain. PPDT measured in Kilopascals (kPa). Three tests applied, which are then mean averaged. Lower PPT indicates greater pain sensitivity.

  Once at baseline

• Temporal Summation

  Temporal Summation as an index of central pain hypersensitivity. Temporal Summation (TS) assessed using a puncate stimulator (designed not to puncture the skin). Participants rate their experience of sharpness during the stimulus on a 10 cm visual analogue scale, first following one application, and second following 10 repeated applications. TS is calculated by subtracting first score from second (in cm). Higher positive scores indicate higher sensitivity.

  Once at baseline

• Conditioned Pain Modulation

  Conditioned Pain Modulation as an index of central pain hypersensitivity. Conditioned pain modulation (CPM) involves temporary ischaemic pain at one arm by way of blood pressure cuff. PPT simultaneously applied to opposite forearm. CPM calculated as conditioned PPT minus non-conditioned PPT in kilopascals (kPa). Lower positive or negative CPM indicates higher sensitivity.

  Once at baseline

• Short Physical Performance Battery Test

  A measure of physical performance of basic physical tasks, which is made up of for tasks:- Standing balance: participants are timed as to how long they can maintain standing balance unassisted without walking aids. First with feet side by side, second in semi-tandem stance, third in full tandem-stance. Points are awarded if balance is maintained for 10 seconds. Walking speed: participants are timed to walk a short distance (3 or 4 meters) at their usual walking pace. Allowed to use their usual walking aids. Points are awarded based on pre-set time scales for completing the walk. Repeated sit to stand: participants timed as to how many times they can sit to stand 5 times from an average height chair. Points awarded based on pre-set durations. Points are combined to give an overall score ranging from 0 - 12. A higher overall score = higher physical performance.

  Once at baseline

• Motor Unit Firing Characteristics of skeletal muscles via High Density Surface Electromyography (HDsEMG)

  Motor unit firing characteristics will be captured using HDsEMG during a range of sub-maximal skeletal muscle contractions. HDsEMG sensor will be placed on the skin over the muscles tibialis anterior and biceps brachii bilaterally to record muscle activation. Established methods will allow analysis of motor unit firing characteristics in terms of size, number, complexity, reliability and firing rate.

  Once at baseline

Secondary Outcomes (8)

• Central Aspects of Pain Questionnaire

  Once at baseline

• Neuromuscular control

  Once at baseline

• Neuromuscular functioning alongside remote pain stimulus

  Once at baseline

• Pain Intensity

  Once via questionnaire prior to objective testing, however current pain level also completed on day of objective testing. Both are at baseline.

• RAND 36 Item Survey 1.0 - Physical Performance sub-scale (SF-36 PF)

  Once at baseline.

Study Arms (3)

Chronic Knee Pain

Adults with knee pain lasting over 3 months

Other: Central Pain Hypersensitivity

Fibromyalgia

Adults with Fibromyalgia

Other: Central Pain Hypersensitivity

Control Group

Adults without chronic pain conditions

Other: Central Pain Hypersensitivity

Interventions

Central Pain Hypersensitivity OTHER

No intervention carried out

Chronic Knee Pain; Control Group; Fibromyalgia

Eligibility Criteria

• Age: 40 Years+
• Sex: all
• Healthy Volunteers: Yes
• Age Groups: Adult (18-64), Older Adult (65+)
• Sampling Method: Non-Probability Sample

Study Population

Participants may be recruited via various routes. Recruitment will primarily be through the Investigating Musculoskeletal Health and Wellbeing (IMH\&W) cohort, which comprises over 7610 people with and without a range of musculoskeletal conditions. Participants with knee pain or fibromyalgia or healthy pain free individuals may be recruited via word of mouth, via University of Nottingham intranet and posters. Participant with fibromyalgia may be recruited to take part via local community support groups.

You may qualify if:

• Knee pain group
• History of knee pain with an intensity level of 4 out of 10 or greater (where 0 is no pain and 10 is the worst pain imaginable) for most days in the past 3 months
• Fibromyalgia group
• Fibromyalgia diagnosis (participant self-reporting a previous diagnosis by a clinician)
• Pain with an intensity level of 4 out of 10 or greater (where 0 is no pain and 10 is the worst pain imaginable) for most days in the past 3 months
• Control group
• \- Pain free individuals without known osteoarthritis

You may not qualify if:

• BMI\>35
• Body weight of 250kg or higher
• Pregnancy (women)
• Inability to give consent
• Inability to meet the requirements of clinical assessment
• Performed strenuous physical exercise in the past 24 hours prior to testing
• Consumed alcohol on day of testing
• Consumed caffeine on day of testing

Sponsors & Collaborators

• University of Nottingham: lead

Study Sites (1)

University of Nottingham Graduate Entry Medicine and Health, Royal Derby Hospital, Uttoxeter Road, Derby

Derby, Derbyshire, DE22 3DT, United Kingdom

RECRUITING

MeSH Terms

Conditions

Fibromyalgia; Chronic Pain

Condition Hierarchy (Ancestors)

Muscular Diseases; Musculoskeletal Diseases; Rheumatic Diseases; Neuromuscular Diseases; Nervous System Diseases; Pain; Neurologic Manifestations; Signs and Symptoms; Pathological Conditions, Signs and Symptoms

Study Officials

• Stephanie Smith, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

• Mathew Piasecki, PhD

  University of Nottingham

  PRINCIPAL INVESTIGATOR

Central Study Contacts

Ben Lightowler, MSc

CONTACT

+44 (0)115 7484098; benjamin.lightowler@nottingham.ac.uk

Stephanie Smith, PhD

CONTACT

+44 (0) 115 823 1942; Stephanie.Smith2@nottingham.ac.uk

Study Design

• Study Type: observational
• Observational Model: CASE CONTROL
• Time Perspective: CROSS SECTIONAL
• Sponsor Type: OTHER
• Responsible Party: PRINCIPAL INVESTIGATOR
• PI Title: Dr Stephanie Smith

Study Record Dates

• First Submitted: November 17, 2025
• First Posted: December 15, 2025
• Study Start: November 24, 2025
• Primary Completion (Estimated): September 1, 2026
• Study Completion (Estimated): September 1, 2026
• Last Updated: December 15, 2025

Record last verified: 2025-12

Data Sharing

• IPD Sharing: Will not share

Locations

GB (1)