Short summary

Patients with lumbar disc herniation suffer from pain and morbidity. Surgical intervetion can be a quick and effective relief, however some individuals experience less favorable outcome.

This study tries to investigate and test the differences in pain perception and pain modulation between individuals. Using PET/CT scans we try to visualize pain perception and -modulation in the CNS. This is subsequently correlated with a battery of pain tests and the surgical outcome of disc herniation surgery.

Rationale

Low back pain (LBP), defined as pain and discomfort located below the costal margin and above the inferior gluteal folds, with or without leg pain, is associated with great morbidity and significant socio-economic impact in many parts of the world. The lifetime prevalence of LBP is reported to be as high as 60-85% and an incidence of 5% per year for adults. 

The underlying pathophysiologies of LBP are many, diverse and often obscure, including: spinal stenosis, infections, inflammation, tumors, fractures, etc. Intervertebral disc herniation (IDH), more specifically lumbar disc herniation (LDH), is a common cause of LBP, irrespective of whether the disc protrudes into the spinal canal and exerts pressure on the lumbar nerve roots or not. It is hypothesized that IDH causes a combination of nerve root ischemia and inflammatory processes leading to neoinnervation and neovascularization, which in turn leads to LBP.

Studies have shown that most LDH can be treated effectively with conservative management and the passage of time. However for the group of patients where pain and disability is of such magnitude or recovery is unacceptably slow, surgical intervention provides effective clinical relief in many cases. Despite the immediate and effective relief often provided by surgery, the literature indicates that it has limited superiority over conservative regimes on the long-term outcome of 1-2 years. Furthermore, as many as 10-40% of patients report unsatisfactory results of lumbar disc surgery, depending on outcome measures. 

Due to this relative high number of unsatisfactory operative outcomes, great emphasis should be put on pre-operative investigation and diagnostics in order to find the candidates who will most likely benefit from surgery and simultaneously identify those where other interventions would lead to greater gain. Currently, magnetic resonance imaging (MRI) is considered the imaging procedure of choice for patients suspected of LDH. However, due to inter-observer variations and the inability to determine the relevance of a pathoanatomical abnormality in relation to clinical symptoms, the need for novel diagnostic tools, in particular imaging, in the selection of operative candidates with IDH remains.

It has been hypothesized that chronic LBP may lead to persistent hyperalgesia, which may in turn adversely affect the efficacy of surgery. Several studies have been performed to investigate the nature and extend of hyperalgesia in relation to LBP. The findings have previously been of conflicting character, however more recent research indicate that hyperalgesia is a common finding in chronic LBP, but does not constitute a separate risk factor. With the increasing availability of functional imaging equipment and novel techniques for monitoring cerebral activity (fMRI, PET, SPECT), new diagnostic opportunities may help shed light on the mechanisms leading to chronic pain, subsequent development of generalized hyperalgesia and affecting the outcome of spinal surgery. 

Unfortunately, structural imaging alone, due to its non-specificity and low sensitivity, is of limited value in this setting. Therefore, there is a dire need for newer approaches that are based on hardcore sciences such as molecular and cellular imaging with PET. The utilization of fMRI-based analysis of pain have been tried and the published data are fairly indefensible, and therefore, new frontiers have to be explored for defining the role of functional imaging in this complicated and disabling source of pain in these patients. Currently there is a lack of data in the literature regarding applications of PET in musculoskeletal disorders, in particular spinal diseases, however previous studies have generated data about the role of PET in assessing the effects of pain in the thalamus.

The objective of this study is to investigate whether quantitative sensory testing (QST) of experimental pain responses and cerebral PET/CT scanning can predict surgical outcome in patients with LDH.

Description of the cohort

Study subjects will be recruited from patients assessed and found eligible for LDH surgery at Spine Center of Southern Denmark, Middelfart, Sygehus Lillebælt. 

Data and biological material

The first 30 individuals participating in the study will undergo a PET/CT scans of their cerebrum and lumbar spine at baseline, 6 weeks and 6 months after surgery. Furthermore, all individuals will undergo a battery of sensory testing to quantify their response to experimental pain stimuli.

All subjects will be followed-up with questionaires regarding their clinical status at both baseline and 1-year after surgery.

Collaborating researchers and departments

Spine Center of Southern Denmark, Lillebælt Hospital

• Associate professor, Senior Consultant Mikkel Ø. Andersen
• Associate professor, chiropractor Søren O'Neill, PhD

Department of Nuclear Medicine, Odense University Hospital

• Professor Poul Flemming Høilund-Carlsen, Dr.Med.

Department of Radiology, Division of Nuclear Medicine, Hospital of the University of Pennsylvania

• Professor Abass Alavi, MD (Hon), PhD (Hon), DSc (Hon)