Neuropathic pain is a chronic pain condition initiated or caused by a primary lesion or dysfunction of the nervous system. The prevalence of neuropathic pain is estimated to be 6-8% in the adult population and accounts for up to 25% of all individuals with chronic pain.
A major reason for the failure to develop effective drug therapy for neuropathic pain has been the difficulty in identifying targets that were truly related to neuropathic pain. The novel approach developed by Dr Okuse and Prof. Rice, disrupting TLPQ-21/ gC1qR interaction by neutralising antibodies, may have promise as a drug target for controlling neuropathic pain.
The team identified gC1qR as the receptor of TLQP-21, a VGF-derived neuropeptide, and found that their direct interaction induces an increase of intracellular calcium in rat macrophages which finally leads to mechanical hypersensitivity in rats. The team then used blocking antibodies against gC1qR which successfully inhibited the response of macrophages to TLPQ-21 and resulted in a delayed onset of nerve injury-associated mechanical hypersensitivity in vivo.
- Our approach focuses on activation of macrophages, previously not studied in the context of neuropathic pain
- VGF has been shown to be upregulated in almost all neuropathic pain models, thus it is the key molecule in neuropathic pain development, unlike many other molecules involved in a specific type of neuropathic pain
- This approach is effective on two points, blocking 1) infiltration of macrophages to sensory nerves and 2) activation of macrophages which leads to secretion of a specific cytokine and hypersensitisation of nociceptive sensory neurons
- Antibodies are specific to targets and tend to show less side effects compared to small molecules
Intellectual property information
Patents: US9718879, EP2807191
Link to published paper
Chen, Y. C., Pristerá, A., Ayub, M., Swanwick, R. S., Karu, K., Hamada, Y., Rice A.C. & Okuse, K. (2013). Identification of a receptor for neuropeptide VGF and its role in neuropathic pain. Journal of Biological Chemistry, 288(48), 34638-34646.