Summary

Cytokines produced within the degenerate disc induce expression of neurotrophic factors and pain related peptides which could be important in nerve ingrowth and pain sensitisation leading to low back pain.

The intervertebral disc (IVD) is considered the largest aneural and avascular structure within the human body, yet during degeneration vascularisation of the IVD is seen to be accompanied by nociceptive nerves. Low back pain is a highly debilitating condition affecting around 80% of the population, 40% of which are attributed to IVD degeneration. Discogenic pain was largely thought to be a result of irritation and compression of the nerve root, yet recent data suggests that pain may be attributed to the sensitisation of sensory nerves by the synthesis of pain related peptides, calcitonin gene related peptide (CGRP) and substance P. It is known that cytokines and chemokines produced by nucleus pulposus cells elicit various effects including the production of matrix degrading enzymes, and decreased matrix molecules. Here, we investigate the hypothesis that cytokines regulate both neurotrophic factor and pain related peptide synthesis within nucleus pulposus and nerve cells which may elicit algesic effects.

Real-Time PCR was performed to investigate gene expression of the neurotrophic factors NGF, BDNF, NT3 and their receptors Trk A, B and C along with Substance P and CGRP on directly extracted RNA from human NP cells and NP cells cultured in alginate for 2 weeks prior to treatment for 48hours with IL-1, IL-6 or TNFα at 0–100ng/mL. Similarly SH-SY5Y neuroblastoma cells were differentiated in retinoic acid for 7 days prior to stimulation with IL-1, IL-6 or TNFα at 0ng/mL and 10ng/mL for 48hours. Immunohistochemistry was used to localise neurotrophic factor receptors Trk A, B and C in both degenerate discs and neuronal cells.

NGF expression was present in normal and degenerate disc samples, however only degenerate discs expressed the high affinity receptor TrkA. Similarly Trk B was present in 22% of normal samples increasing to 100% expression within degenerate disc samples. All cytokines increased expression of NGF in NP cells (P≤0.05). TNFα also increased BDNF significantly, whereas no significant affects were seen in NT3 expression in NP cells. Trk B expression was significantly increased by IL-1 and TNFα treatment of NP cells. Conversely Trk C was down regulated by IL-6. Substance P was significantly increased by IL-1 and TNFα treatments whilst IL-6 and TNFα increased CGRP expression in NP cells. In SH-SY5Y cells, IL-1 significantly increased BDNF whilst IL-6 and TNFα failed to induce significant differences in neurotrophic factors. All cytokines increased Trk expression in the nerve cell line; however this failed to reach significance. Immunohistochemistry confirmed the presence of Trk receptors within the neuronal cell line.

Here we have demonstrated that a number of cytokines known to be up regulated during disc degeneration and disc prolapse, induce expression of various neurotrophic factors, their receptors and pain related peptides within human NP cells, as well as SH-SY5Y cells. This data suggests that the presence and production of cytokines within the degenerate disc may be responsible for nerve ingrowth and sensitisation of nerves which may result in discogenic pain.

Spinal disc infection is associated with a significant morbidity and mortality in the acute setting. On long term review it leads to significant moribidity due to the deformity and secondary osteoarthritic changes in the surrounding vertebral segments.

Prospective collection of data of 21 patients suffering from discitis was collected over the span of last 10 years. The age group ranged between 21 -67 yrs. The male: female ratio was 1.2:1. The minimum delay in presentation since the onset of symptoms was 8 weeks. The detection of the micro-organism was either by needle/open biopsy or indirectly via blood cultures. Serial records were maintained of inflammatory markers. All patients received plain radiographs, gadolinium-enhanced magnetic resonance imaging scans, and bone/gallium radionuclide studies

Operative decompression was performed in 7 patients. Infection elsewhere was the most common predisposing factor. Leukocyte counts were elevated in 54% of spondylodiscitis cases. The erythrocyte sedimentation rate and CRP were elevated in all cases of epidural abscess. The most common organism was Staph Aureus. Antibiotics were administered for duration of at least 6 weeks. On long term, all patients developed deformity at the level of the infection, with half of them being symptomatic.

Spinal infections are extremely morbid conditions demanding prompt diagnosis and urgent treatment to prevent complications.

Ethics approval: Audit Committee Interest statement: No conflict of interest

Lumbar decompression-fusion surgery involves extensive surgery in prone position and is associated with significant post-op ileus. We compared the post-operative oral intake regimes of our two spinal firms over a 6 months period.

The post operative oral intake was commenced as soon as the bowel sounds started in one firm. In the other firm, the oral intake was started only after the patient passed wind. There were 28 patients in the first group (bowel sounds) and 27 patients in the second group (passage of wind). The two groups were comparable for age and sex distribution. The average age was 69 yrs, and the male: female ratio was 1.2:1.

The bowel sounds were found to start on an average of 8.5 hours (6-16 hours) post-operatively. The average time between the operation and the patient passing wind was 26 hours (18-73 hours). The patients who were on Patient Controlled Analgesia (PCA) were found to have a delayed passage of wind. There was no significant correlation between the number of fusion levels or the operative time and commencement of bowel sounds/ passage of wind

The patient satisfaction rate was much better when the oral intake was commenced as soon as the bowel sounds start. The incidence of nausea/vomiting was significantly less in the group in which the oral intake was commenced following patient passing wind. The bloating of the abdomen was found in the first group.

Audit Committee Interest statement: No conflict of interest