A while back I did a PhD in neuroscience. My work was focused mostly on the molecular mechanisms of nociception in the peripheral nervous system. At that time it was not clear which receptors would be a good clinical target for pain treatments. In the meantime it looks like the pharmaceutical companies had good results with two targets: CGRP (calcitonin gene-related peptide) for the treatment of migraines and NGF (nerve growth factor) for the treatment of pain due to osteoarthritis.
The CGRP antibodies and the CGRP receptor antibodies are on the market already (an overview here). One of the CGRP receptor antibodies is erenumab. The clinical studies are really good. In the STRIVE trial “a 50% or greater reduction in the mean number of migraine days per month was achieved for 43.3% of patients in the 70-mg erenumab group and 50.0% of patients in the 140-mg erenumab group, as compared with 26.6% in the placebo group (P<0.001 for each dose vs. placebo)” . You can read The New England Journal of Medicine article on STRIVE trial here. But also there are concerns about safety: see articles here and here. It is really interesting how we got to CGRP as a target for the treatment of migraines (see this article). The mechanism of migraines is not clearly understood, but it seems that one cause is a seizure like activity called cortical spreading depression (CSD) that starts in the occipital lobe. The CSD triggers the clinical migraines by irritating the trigeminovascular system. Initially, substance P was thought to be important in causing migraines, but targeting substance P failed. Then, the attention moved to CGRP because it was found to be elevated in the blood during severe migraine attacks.
The NGF antibodies for the treatment of pain due to osteoarthritis are still under study in clinical trials. One NGF antibody is tanezumab. Concerns about safety abound: articles here and here. As the name nerve growth factor suggests, NGF is important for neuronal survival but also for the pancreas and the immune system. Maybe it will be a matter of finding a dose that has benefit and minimal side effects.