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

Investigating the Role of Central Pain Hypersensitivity in Skeletal Muscle Neural Drive, in People With Knee Pain, and in People With Fibromyalgia Syndrome (Pain-Neural Drive)

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.

Participants will be required to attend two visits to Derby Medical School.

Screening and eligibility assessment:- Prior to booking an appointment to attend the study, potential participants will be given the opportunity to ask questions and be pre-screened for eligibility for the study.

Participation involves two study visits:- Visit 1 involves screening for eligibility, and providing informed consent. A brief history of pain condition and clinical knee assessment will be carried out. Familiarisation with the muscle testing protocol (practicing a set of muscle contractions) a questionnaire booklet will be provided at this visit. Visit 1 will last between 30 and 45 minutes.

Visit 2 is the test session. Body weight and height will be taken. Pain sensitivity testing (quantitative sensory testing) will be followed by neuromuscular testing while sitting in a specially designed chair. Isometric muscle contractions will be measured using an isometric dynamometer. One muscle will be tested in the lower legs and one muscle in the upper arms (on both sides).

Electrodes will be placed on a muscle at the front of the leg (tibialis anterior) and at the front of the upper arm (biceps brachii). A battery of isometric (static) muscle contractions will be performed following a force trace visual feedback on a monitor. 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 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.

Physical performance and self-reported physical functioning and disability will be measured with a simple performance measure and questionnaires respectively. A pre-test questionnaire will be used to collect relevant data, including: pain severity, duration of pain condition, duration of pain, other medical conditions, gender, ethnicity, smoking status, employment status, use of pain medications. The questionnaire also includes validated questionnaires on quality of life, central aspects of pain, disability, physical functioning, fatigue and physical activity.

Inclusion Criteria:

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

Exclusion Criteria:

• 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