Factors predicting the transition from acute to persistent pain in people with 'sciatica' - the FORECAST study

Sciatica is a term used to describe painful symptoms affecting the hips, buttocks and legs. It is caused by injured or irritated nerves in the lower back. Sciatica pain can feel hot, sharp, or electrical in nature. Sciatica can also cause weakness and pins and needles. Sciatica is a complex condition and the pain may be caused by different mechanisms in different patients. We still do not fully understand the exact mechanisms of sciatica pain.

Sciatica is a very common condition and can have a devastating effect on everyday life. For example, some patients lose their independence and need help with day-to-day tasks such as dressing. Sadly, approximately one in three patients with sciatica develop persistent sciatica pain.
We currently do not understand why some patients develop persistent sciatica pain and why some recover. Previous research has demonstrated that usual clinical findings (e.g., presence of depression or changes on a standard MRI scan) cannot predict persistent sciatica pain. Therefore a different approach is required to identify patients who may develop persistent sciatica pain. This is the goal of the FORECAST study.

Previous studies only included a short clinical examination. Our study is different. We will perform a detailed set of tests (see below). Our ambition is that the detailed tests can predict who will develop persistent sciatica pain. The questions we plan to answer in the FORECAST study are:
1. Can the detailed tests identify patients with similar mechanisms causing their sciatica pain?
2. Which of these detailed tests predict persistent sciatica pain?

The FORECAST study is performed by a team of medical doctors, neuroscientists, statisticians and magnetic resonance imaging (MRI) specialists at Oxford University. The team also includes patient partners. They help us to make sure our study is useful for patients.

We will invite 180 patients with recent onset of sciatica pain (<3 months) to participate in the FORECAST study. At their initial assessment, we will perform the detailed tests. This includes detailed sensory nerve testing (quantitative sensory testing). Quantitative sensory testing evaluates how well patients can feel different stimulations such as cold, warm or pressure. This tells us how well the nerve is working and how sensitive it has become. We will also include a precise set of questionnaires to evaluate the types of pain (e.g., burning or electric shock or achy) and emotional wellbeing. Emotional wellbeing can be affected when a patient has sciatica. For instance, some patients may be anxious or angry, and others may feel lonely and detach themselves from friends and family. We will also take a blood sample to look for signs of inflammation. In some patients we will use specialised MRI scans. These images are much more detailed and specialised than standard MRI scans. They allow us to evaluate the microscopic structure of the small nerves in the back, which is not possible with standard MRI scans. These detailed tests will provide us with a good picture of the starting point of a patient's experience of sciatica.

We will then contact patients again three months and one year later, to ask whether they still have sciatica pain. We will use statistics to identify patients with similar mechanisms causing their sciatica pain. We will also examine which tests predict persistent sciatica pain.

The results of the FORECAST study will help us better understand the complexity of sciatica and who will develop persistent pain. Our findings will also help future research. For example, future studies can examine whether we can prevent or reduce persistent pain by giving more specific treatment to patients who the FORECAST study shows are likely to develop persistent sciatica pain. We hope that the results of the FORECAST study will help reduce suffering and improve quality of life for patients with sciatica.

Sciatica is a common condition (43% lifetime prevalence) and is associated with higher levels of pain, disability, poorer quality of life, and increased use of health resources compared to low back pain alone. Although many patients recover, a third develop persistent sciatica symptoms. Unfortunately, it remains unclear, why some patients develop persistent sciatica as none of the traditionally considered clinical parameters (e.g., symptom severity, routine magnetic resonance imaging, depression) are consistent prognostic factors. Given the failure of traditional variables as prognostic factors, a novel approach is required to understand who may develop persistent pain.

FORECAST includes a prospective prognostic cohort study that aims to:
1. Explore mechanism-based subgroups in patients with sciatica, using deep phenotyping.
2. Investigate whether a mechanism-based approach can identify factors that predict pain persistence in patients with sciatica.

We will evaluate prognostic factors for pain persistence in n=180 patients with acute/subacute sciatica. Prognostic variables will be assessed at baseline and outcome at 3 and 12 months. This will include self-reported sensory and psychosocial profiles, quantitative sensory testing, blood inflammatory markers and advanced neuroimaging. We will use principal component analysis followed by clustering methods to identify subgroups. Univariate associations and machine learning methods optimised for high dimensional small datasets will be used to identify the most powerful predictors and model selection/accuracy.
This project is based on our strong feasibility data and has been shaped by in-depth patient involvement. The results will provide crucial information about the pathophysiological drivers of sciatica symptoms and identify prognostic factors of pain persistence. This will ultimately facilitate patient stratification and streamline management pathways to increase quality of life for patients with sciatica.