Study of Nerve Injuries and Physical Exercise

This study will explore if combining exercise with sensory training can help improve sensory function and reduce pain after an injury to the nerves in the arm and hand. The study will look at how exercise affects the BDNF protein (which helps nerves grow), how it impacts sensation, and how it might help manage pain. Research has shown that exercise is good for brain health, enhancing abilities such as focus, memory, and the ability to cope with stress. It also helps the brain release BDNF, which helps nerve cell growth and plasticity. Higher levels of BDNF might improve sensory function, but no previous study has investigated the combination of exercise and sensory training.

Study aims to investigate:

* if it is possible to use a physical exercise program (using an exercise bike) for people with nerve injuries.
* how easy it is to recruit participants, how well they stick to the program
* if exercise can change BDNF levels and VO2max (a measure of fitness), and how these changes might relate to pain and sensory.
* if it's possible to run a bigger, more detailed study in the future and check if it could be helpful for patients.

The researchers believe that combining exercise with sensory training could help reduce pain and improve sensation compared to traditional sensory training methods.

Participants will:

* perform 30 minutes of exercise on a stationary bike, twice a week, for 6 weeks at a moderate level of effort. After the exercise, they will do 5-10 minutes of sensory training, with additional exercises to practice at home. The sensory training will follow a standard program designed to help retrain the brain to process sensory information.
* be subject to a blood sample Results will include sensory function, pain evaluation, patient reported outcome measures.

Hypothesis The hypothesis posits that integrating physical exercise with sensory relearning may lead to a reduction in pain and an improvement in sensory interpretation. Potentially, adding physical activity both during the early and later stages of rehabilitation following PNI in the arm and hand could be beneficial, in comparison to only conventional sensory relearning. This study is planned as a feasibility study to investigate the possibility of using physical activity. The results, knowledge and insights from this study will be used in the design of a future RCT study at our clinic.

Aim The primary aim of this study is to evaluate the feasibility of implementing a structured physical activity program, using an exercise bike, after PNI in the arm and hand in a rehabilitation setting at the hand surgery department at Sodersjukhuset. The study is set out to assess the recruitment, retention rates and possible outcome measures, prior to design of a RCT. Further, the study will explore the responsiveness in pre- and post-intervention testing and the acceptability in the outcome measures. It will explore potential trends in BNDF and Vo2max changes and its potential correlation with pain and sensory function.

Study population

Recruitment of study population Patients with pain and/or decreased sensory function after a PNI in the arm and hand will be included. Health care practitioners at the department of Hand Surgery at Sodersjukhuset will identify potential participants that meet the study inclusion criteria either through search of medical journals or during visits at the hand surgery unit. An invitational letter with a description of study including a letter of consent will be handed to the patient personally or by mail and we will follow up with a telephone call. Intervention The participants will perform supervised physical exercise on a stationary exercise bike, 30 minutes, 2 times a week, for 6 weeks. The exercise will be at moderate intensity (40-59 % VO2max). The exercise will be held at the department of hand surgery at Sodersjukhuset, supervised by a physiotherapist. The intervention will be modified according to the physical ability of the participant. Immediately after the exercise, sensory relearning exercises will be performed for about 5-10 minutes. In addition, the participants will perform the sensory relearning at home. To conduct sensory relearning in brief periods at home, 4-5 times a day has been shown to be effective in previous studies following median nerve injuries (25). Multisensory early sensory relearning is carried out according to standardized sensory relearning protocol, appendix 1, (Kansletraningsinformation). Organization of the work The intervention starts with a familiarization session and introduction to the testing procedures and equipment. Oral and written information regarding the study will be provided by the treating therapist and a written consent will be obtained before the familiarization session starts. The questionnaires will be sent out before the first study visit. Baseline measures will be taken during session number two and will be conducted by the physiotherapist and co-researcher. The same procedure with measurements will be conducted after 6 weeks and a follow up at 12 weeks, see timeline (appendix 2 Flowchart). Baseline measures for BDNF will be measured before and after the first bike session at 3, 6, and 12 weeks. At each time point, a nurse will draw 10 mL blood sample and divide it into two separate containers (a heparinixed tube for plasma and a clot activator tube for serum analysis). The blood collected for plasma will be centrifuged at 6000 rpm (revolutions per minute) for 3 min, to separate the plasma while the tube for serum analysis will be left for at least 30 min to clot at room temperature, before being centrifuged at 6000 rpm for 15 min to separate the serum. Thereafter, both separated plasma and serum samples will be transferred to Eppendorf tubes, pseudonymized and provided with a code at the hand surgery department Södersjukhuset. The samples will then be transported to The Swedish School of Sport and Health Sciences where they will be stored at -80°C until analysis. Neurotrohic factors will be analysed using ELISA kits following the manufacturer´s instructions.

All the questionnaires will be sent out prior to the study by mail or electronically. All tests will be performed: Before intervention, 3 weeks, 6 weeks and 12 weeks.

Drop out and study adherence will be investigated with open-ended questions e.g. describe in your own words why you decided to end/continue the study participation.

Eligibility Criteria:
Inclusion Criteria:

* Patients with peripheral nerve in the arm and hand, treated at the rehabilitation unit at Södersjukhuset, between 2010-2025
* 14 days to 15 years after injury.
* Age above 18.

Exclusion Criteria:

* Psychiatric illness or substance addiction severe enough to make intervention impossible.
* Severe neurological disease.
* Severe diabetes mellitus with nerve complications.
* Severe cardiovascular disease where aerobic exercise is contraindicated.
* Unwillingness or medical inability to undergo the intervention.
* Insufficient knowledge of the Swedish or English language, which makes examination with patient-reported questionnaires impossible.