Pathomechanism of pain-related behavior produced by allografts of intervertebral disc in the rat

Mamoru Kawakami*, Tetsuya Tamaki, James Neil Weinstein, Hiroshi Hashizume, Hideto Nishi, Stephen T. Meller

*Corresponding author for this work

    Research output: Contribution to journalArticlepeer-review

    160 Scopus citations


    Study Design. This study was designed to evaluate whether allografts of intervertebral disc materials produce hyperalgesia in the rat and whether an immune response, pH, or chemicals correlate with the induced hyperalgesia. Objective. To elucidate the pathomechanisms of radicular pain secondary to lumbar disc herniation. Summary of Background Data. It has been reported that a low pH, an autoimmune reaction, or chemical radiculitis is likely responsible for radicular pain associated with lumbar disc herniation. In animal studies, it has been shown that hyperalgesia (an increased sensitivity to painful stimuli) involves activation of phospholipase A2 and nitric oxide synthase. Methods. Fat, nucleus pulposus, and anulus fibrosus were allografted into the epidural space at L6 in the rat. Withdrawal response thresholds to mechanical stimuli and withdrawal response latencies to thermal stimuli on the tail and pH in the applied tissues were measured after surgery. Interleukin-1, phospholipase A2, and nitric oxide synthase were examined in the applied tissues using immunohistochemistry, nicotineamide adenine dinucleotide phosphate-diaphorase histochemistry, and in situ hybridization. Results. Allografted fat did not produce hyperalgesia. Allografts of nucleus pulposus and nucleus pulposus plus anulus fibrosis showed evidence of mechanical and thermal hyperalgesia, respectively. There were no observed changes in pH over time. Although interleukin-1 was demonstrated in all applied tissues, phospholipase A2 was only observed around the applied nucleus pulposus and nucleus pulposus plus anulus fibrosus. Nitric oxide synthase was only markedly increased around the applied tissues. Conclusion. The nucleus pulposus and anulus fibrosus produce different forms of hyperalgesia (mechanical vs. thermal) associated with different and distinct immunohistochemical changes. It is possible that radicular pain of a lumber disc herniation results from chemicals, such as phospholipase A2 and nitric oxide.

    Original languageEnglish (US)
    Pages (from-to)2101-2107
    Number of pages7
    Issue number18
    StatePublished - Sep 15 1996


    • hyperalgesia
    • interleukin
    • intervertebral disc
    • nitric oxide (NO)
    • pH
    • phospholipase A (PLA)

    ASJC Scopus subject areas

    • Orthopedics and Sports Medicine
    • Clinical Neurology


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