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

Trial statusRecruiting
Trial phaseNot listed
Trial typeObservational
Biological sexAll
Age40+
SponsorUniversity of Nottingham

About this trial

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.

Eligibility criteria

This trial accepts healthy volunteers

Qualifiers

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 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

Disqualifiers

BMI>35

Body weight of 250kg or higher

Pregnancy (women)

Inability to give consent

Trial 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.

Trial design

Design model

Case-control

Time perspective

Cross-sectional

Treatments tested in this trial

  • Central Pain Hypersensitivity

    Other intervention

    No intervention carried out

Treatment groups

135 Participants
are divided into 3 treatment groups
Group A: Chronic Knee Pain1 intervention
Group B: Fibromyalgia1 intervention
Group C: Control Group1 intervention

Trial outcomes

Primary outcomes

1

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.

Time frame
Once at baseline
2

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.

Time frame
Once at baseline
3

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.

Time frame
Once at baseline
4

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.

Time frame
Once at baseline

Secondary outcomes

1

Central Aspects of Pain Questionnaire

A self completed questionnaire giving a central aspects of pain factor, an index of central nervous system aspects of pain. The questionnaire includes 8 items covering neuropathic-like pain, fatigue, cognitive difficulty, catastrophizing, anxiety, sleep disturbance, depression and widespread pain. For the former 7 items, respondents rate the frequency of experiencing symptoms over the past week with four options "never", "sometimes", "often", "always". The widespread pain item involves shading areas of a manakin relating to painful areas of the body experienced on most days in the last four weeks. All items are combined to give an overall score. Scores can range from 0 to 16. The higher the score, the greater the central aspects of pain factor.

Time frame
Once at baseline
2

Neuromuscular control

A range of isometric muscle contraction patterns will be performed (tibialis anterior and biceps brachii) in terms of contraction strength, duration and rate of force generation. Neuromuscular control metrics will include force steadiness, and force accuracy.

Time frame
Once at baseline
3

Neuromuscular functioning alongside remote pain stimulus

To test whether experimental remote pain has an influence on neuromuscular functioning, a temporary pain stimulus will be applied to the arm via blood pressure cuff to a subjective level of 4/10 where '0' no pain and '10' worse pain or discomfort imaginable. A series of isometric (static) muscle contractions will be carried out during the remote discomfort stimulus lasting approximately 2 minutes. If discomfort becomes too much at any time the cuff will be removed immediately. The effect of remote pain stimulus on neuromuscular functioning will be analysed in terms of neuromuscular control (including force steadiness, and force accuracy) and motor unit firing characteristics (using HDsEMG).

Time frame
Once at baseline
4

Pain Intensity

Pain intensity measured by self-report using an 11 point numerical rating scale from 0-10, where 0 is no pain and 10 is the worst pain imaginable. Three items will be administered, using the 11 point scale detailed above:- * Over the past 4 weeks, how strong was your strongest pain? * Over the past 4 weeks, how strong was your pain on average? * How would you assess your pain now, at this moment?

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

Other outcomes

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