The origin of
pain in
osteoarthritis is poorly understood, but it is generally thought to arise from
inflammation within the innervated structures of the joint, such as the synovium,
capsule and bone. We investigated the role of
nerve growth factor (
NGF) in
pain development in murine OA, and the
analgesic efficacy of the soluble
NGF receptor, TrkAD5. OA was induced in mice by destabilisation of the medial meniscus and
pain was assessed by measuring hind-limb weight distribution.
RNA was extracted from joints, and
NGF and TNF expressions were quantified. The effect of tumour
necrosis factor (TNF) and neutrophil blockade on
NGF expression and
pain were also assessed.
NGF was induced in the joints during both post-operative (day 3) and OA (16weeks)
pain, but not in the non-painful stage of disease (8weeks post-surgery). TrkAd5 was highly effective at suppressing
pain in both phases. Induction of
NGF in the post-operative phase of
pain was TNF-dependent as anti-TNF reduced
NGF expression in the joint and abrogated
pain. However, TNF was not regulated in the late OA joints, and
pain was not affected by anti-TNF
therapy.
Fucoidan, by suppressing cellular infiltration into the joint, was able to suppress post-operative, but not late OA
pain. These results indicate that
NGF is an important mediator of OA
pain and that TrkAd5 represents a potent novel
analgesic in this condition. They also suggest that, unlike
post-operative pain, induction of
pain in OA may not necessarily be driven by classical inflammatory processes.