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THE EFFECT OF NEUROTROPIN® ON PROTEOGLYCAN AND COLLAGEN SYNTHESIS BY INTERVERTEBRAL DISC CELLS: GP36.

Yoshikawa, Tomoaki1; Hemmad, Aseem1; Naiki, Mitsuru2; Uchida, Atsumasa3; Masuda, Koichi1

Spine Journal Meeting Abstracts: October 2011 - Volume - Issue - [no page #]
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1University of California, San Diego, Orthopaedic Surgery, La Jolla, US; 2Nippon Zoki Pharmaceutical Company, Institute of Bio‐Active Science, Katoh‐shi, Hyogo, Japan;

3Mie University Graduate school of Medicine, Tsu, Mie, Japan

INTRODUCTION: Neurotropin® (NTP) is a nonprotein extract from the inflamed skin of rabbits following inoculation with vaccinia virus and has been widely used to treat neuropathic pain, including post‐herpetic neuralgia and low back pain in Japan [1]. Animal models have shown that the anti‐nociceptive effect of NTP was derived from the activation of the descending monoaminergic pain inhibitory system. The purpose of this study was to assess the effects of NTP on proteoglycan (PG) and collagen synthesis using bovine nucleus pulposus (NP) and anulus fibrosus (AF) cells cultured under normoxic and hypoxic conditions.

METHODS: Bovine NP and AF cells in alginate beads were treated with three different concentrations (0.001‐0.1 NU/mL) of NTP for three days under normoxic (21%O2) or hypoxic (5%O2) conditions; PG and collagen synthesis and cell proliferation were assessed. (cont'd)

RESULTS: PG synthesis was significantly increased with NTP treatment in NP cells under culture at 5% O2 (at 0.1 NU/ml, +66%, p<0.05, Figure ). Collagen synthesis in AF cells under 21%O2 was increased by treatment with NTP in a dose‐dependent manner (at 0.1 NU/ml: +47%, p<0.05, Figure).

DISCUSSION: NTP stimulated extracellular matrix synthesis of intervertebral disc cells to different degrees in normoxia and hypoxia; NP cells responded better under hypoxic conditions while AF cells responded better under normoxic conditions. Because oxygen tension is different in the AF and the NP, these differential responses by two different cell types may reflect optimal culture conditions. The mechanism of increased extracellular matrix production by NTP is not clear at this point; further studies on the mechanism are warranted. Our results suggest that NTP may have beneficial effects, not only on pain relief, but also on maintaining intervertebral disc homeostasis. An in vivo study on this aspect of treatment with NTP is of clinical interest.

© 2011 Lippincott Williams & Wilkins, Inc.