NERVE INGROWTH INTO DISEASED INTERVERTEBRAL DISC IN CHRONIC BACK PAIN

Background In the healthy back only the outer third of the annulus fib rosus of the intervertebral disc is innervated. Nerve ingrowth deeper into diseased intervertebral disc has been reported, but how common th is feature is and whether it is associated with chronic pain are unkno wn. We examined nerve growth into the intervertebral disc in the patho genesis of chronic low back pain. Methods We collected 46 samples of i ntervertebral discs from 38 patients during spinal fusion for chronic back pain. 30 samples were from pain levels clinically established by discography and 16 samples were from adjacent vertebral levels with no pain. We obtained 34 control samples of intervertebral disc from prev iously healthy individuals with normal histology within 8 h of recorde d death. We used standard immunohistochemical techniques to test for a general nerve marker, a nociceptive neurotransmitter (substance P), a nd a protein expressed during axonogenesis (growth-associated protein 43 [GAP43]). Findings We identified nerve fibres in the outer third of the annulus fibrosus in 48 (60%) of the 80 samples of intervertebral discs. Nerves were restricted to the outer or middle third of the annu lus fibrosus in the 34 control samples. Among the patients with chroni c low back pain, nerves extended into the inner third of the annulus f ibrosus and into the nucleus pulposus in 21 (46%) and ten (22%) sample s, respectively. Nerves usually accompanied blood vessels, but in 14 o f the samples from back-pain patients, isolated nerve fibres were seen in the discal matrix. Both types of nerve fibres expressed substance P, but only non-vessel-associated fibres expressed GAP43, Deep nerve i ngrowth into the inner third of the annulus fibrosus, the nucleus pulp osus, or both was seen in four (25%) of 16 biopsy samples from non-pai n levels and in 17 (57%) samples from pain levels. Of the 16 paired sa mples from both pain and non-pain levels, five pain-level samples and one non-pain-level sample showed deep nerve ingrowth. Interpretation O ur finding of isolated nerve fibres that express substance P deep with in diseased intervertebral discs and their association with pain sugge sts an important role for nerve growth into the intervertebral disc in the pathogenesis of chronic low back pain.