The Science Behind Librela

Librela acts by binding to a substance the body makes called nerve growth factor(NGF), making it biologically inactive. NGF does many things for the nervous system from pain signaling to repair and maintenance of homeostasis. And there are many things it does that we are most likley unaware of.

Here is a summary of the physiological mechanisms involved with NGF from Curtis Dewey, a board certified neurologist, including references:

“The nerve growth factor (NGF) pathway is a major (perhaps the major) pain conducting pathway for joints and bones. Osteoarthritis (OA) is very common in dogs and cats, especially as they grow older. Painful signals are transmitted through sensory nerves associated with various regions of the affected joint(s) (e.g., periosteum, synovium, articular cartilage, subchondral bone, etc.). Several damaging events occur in OA, including loss of articular cartilage and microfractures in the bone beneath the cartilage (subchondral bone). As OA progresses, NGF levels increase in the affected joint(s) and sensory nerve endings and their receptors proliferate. These structural changes lead to progressive amplification of pain signals. This is why the pain of OA progresses over time. It is well established that most of these painful stimuli are transmitted by NGF interacting with its receptors (primarily the TrkA receptors) in sensory nerve endings. So far, it should make sense that blocking NGF with an injectable monoclonal anti-NGF antibody drug (Librela for dogs, Solensia for cats) relieves OA-associated pain in many pets with arthritis. There is a potential downside to this inhibition, and it is not simply that the pain relief afforded by the drug may lead to excessive forces being placed on compromised joints. Those same sensory nerves transmitting pain signals to the spinal cord following NGF interaction with its TrkA receptors also release several protective factors into the area of the joint that are necessary for repair/healing of the affected joint. In other words, the same NGF/TrkA mediated nerve stimulation responsible for transmitting pain signals is necessary for maintenance and healing of the OA joint. In addition to this neural protective mechanism, there are local NGF-mediated non-neural pathways (in the region of the joint) that limit inflammation and promote healing of damaged joint structures (e.g., cartilage, subchondral bone). Most of these local pathways are mediated via the other main NGF receptor, the p75NTR receptor, which is also blocked by Librela/Solensia. Theoretically, blocking all the NGF-mediated pathways with a monoclonal antibody, though likely to provide pain relief, could predispose some patients with OA to experience accelerated joint damage. This is what happened to some human patients during clinical trials of the anti-NGF drug tanezumab (the human version of Librela/Solensia) and it is the main reason that the drug was not approved for human use. This catastrophic breakdown of joint structures is termed rapidly progressive osteoarthritis (RPOA) and something very similar has been observed in dogs and cats treated with Librela and Solensia, respectively. The pathways mediated by NGF are not theoretical. I am working on a review article that is much more technical than this description. So far, I have found (via an extensive literature search) 10 major joint anabolic/protective signaling pathways that are promoted by NGF and 2 catabolic/destructive signaling pathways that are inhibited by NGF I added a table I made, listing these signaling pathways. I have listed a few key references below.”

1. Rosen V, Gori F. Not just a pain in the bone: growth factors secreted by sensory nerves promote fracture healing. Science, 2026.

2. Zhao L, Lai Y, Jiao H, Huang J. Nerve growth factor receptor limits inflammation to promote remodeling and repair of osteoarthritic joints Nature Communications, 2024.

3. Li Z, Meyers CA, Chang L, et al. Fracture repair requires TrkA signaling by skeletal sensory nerves. J Clin Investig, 2019.

4. Rivera KO, Cuylear DL, Duke VR, et al. Encapsulation of β-NGF in injectable microrods for localized delivery accelerates endochondral fracture repair. Front Bioeng Biotech, 2023.

5. Wang M, Lian J, Ye M, An B. Pain mediator NGF improves chondrocyte extracellular matrix synthesis via P13K/AKT signaling pathway. J Orthop Surg Res, 2025.