On the contrary, the same dose of hNGFp administered intranasally, which was rather widely biodistributed in the brain and did not induce pain sensitization, blocked APP processing into amyloid and restored synaptic plasticity and memory in this aggressive neurodegeneration model.
Furthermore, PAF remained stable following NGF injection, indicating that the presence of NGFpain for multiple weeks is not sufficient to induce the PAF slowing reported in chronic pain.
Moreover, the NGF antibody tanezumab has provided clinical proof of concept for inhibition of the TrkA kinase pathway in pain leading to significant interest in the development of small molecule inhibitors of TrkA.
This double-blinded, randomized study assessed pain and muscle hypersensitivity after a single-site bolus NGF injection (5 µg) compared with 5 spatially distributed, low-dose NGF injections (1 µg, 4 cm distance) into the tibialis anterior (TA) muscles in 20 healthy subjects.
A variety of pharmacological options have been investigated in treating OA, including existing therapies previously used for treating other arthritides (such as colchicine and hydroxychloroquine) and new therapies targeting pain (including monoclonal antibodies to nerve growth factor and intra-articular trans-capsaicin).
Higher NRS pain scores of ischaemic-contractions were seen when contracting the muscle injected with NGF compared to baseline (p = .003) and control (p = .012).
Together, this provides evidence that PPS may act to suppress the release of NGF in the subchondral bone to ameliorate pain associated with knee osteoarthritis.
A point mutation (R100W) in the NGFB gene was found in patients with Hereditary Sensory and Autonomic Neuropathy type V (HSAN V), which leads to pain insensitivity.
Nerve growth factor antibody for the treatment of osteoarthritis pain and chronic low-back pain: mechanism of action in the context of efficacy and safety.
Results suggest that anti-NGF agents may prove to be novel additions in helping to optimize pain relief in cancer patients who fail to respond adequately to opioids and other common co-analgesics.
The up-stream activator of mechanoflammation remains unknown, but it results in rapid activation of NFkB and the inflammatory mitogen activated protein (MAP) kinases and this controls the bioavailability of aggrecanase and regulation of nerve growth factor (NGF), causing pain.
Intramuscular administration of nerve growth factor into masseter muscle causes inhibitory corticomotor plasticity, which likely occurs to prevent further damage and seems associated with lower pain intensity on function.
The physiological function of NGF as a pain mediator is altered in patients with Hereditary Sensory and Autonomic Neuropathy type V (HSAN V), caused by the 661C>T transition in the <i>Ngf</i> gene, resulting in the R100W missense mutation in mature NGF.
The significance of these findings is at least two folds: 1) the NGF<sup>R100W</sup> mutation can be used as an alternative to the wildtype NGF to treat human conditions without eliciting pain; and 2) the 75 kDa neurotrophic factor may serve as a novel target for pain management.
Sustained release of TAA locally in the IVD appeared safe and reduced NGF expression, suggesting its potential applicability for pain relief, although beneficial effects were absent on tissue degeneration.