Dogs with bone cancer suffer with severe pain due to widespread somatosensory sensitivity. Through a combination of peripheral sensitisation, central sensitisation and deficiencies in the endogenous analgesic system this severe pain is refractory to conventional therapy and palliative analgesia (Monteiro et al 2018). Endogenous levels of nerve growth factor (NGF) are increased in a range of painful conditions, including cancer (Enomoto et al 2019).
In a murine model of bone cancer it was demonstrated that osteosarcoma cells induce sprouting of sensory and sympathetic nerve fibres in the periosteum under the influence of NGF (Mantyh et al 2010). Administration of an anti-NGF therapy reduced this pathological sprouting and inhibited the generation and maintenance of cancer pain in this study. Further work shows that preventive use of an anti-NGF antibody blocks ectopic sprouting and significantly attenuates the genesis and severity of cancer pain in mice (Jimenez-Andrade et al 2010).
Bedinvetmab is a canine specific monoclonal antibody which targets nerve growth factor, with a license for the treatment of pain of osteoarthritis (OA) in dogs. Efficacy for reduction of OA pain has been demonstrated versus placebo (Summary of Product Characteristics) using the Canine Brief Pain Inventory, a pain score validated for assessment of OA pain in dogs (Brown et al 2008).
Over 50% of sensory nerve fibres which innervate bone are CGRP+ fibres, meaning they co-express the TrKA receptor. Therefore therapies that target NGF or TrKA are expected to be particularly efficacious (Mantyh 2010). The majority of canine osteosarcoma tumours express the TrkA protein, therefore anti-NGF could provide significant relief against bone cancer pain and potential slow rate of tumour growth (Demir et al 2016).
In recent cases we have included bedinvetmab as part of our analgesic plan for cases of osseous neoplasia. Typically these cases are incredibly painful and the pain is difficult to control. Our experience to date is to include anti-NGFs, NSAIDs where possible, gabapentinoids, ketamine and nerve blocks. We recently presented this work as a poster (Vigevani et al 2022) at the ESVONC conference. Further work is required in a prospective study and we believe there is justification for the use of anti-NGFs in osseous neoplasia.
This post was written by Matt Gurney.
Matt sees referrals in the pain clinic at Anderson Moores Veterinary Specialists. You can also receive telemedicine advice from us here if you have a pain case where you need a helping hand.
Matt & Carl established Zero Pain Philosophy to provide educational resources & telemedicine to veterinary professionals enabling optimal management of pain.
Matt Gurney is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and works at Anderson Moores Veterinary Specialists. Matt is President of the European College of Veterinary Anaesthesia & Analgesia.
Carl Bradbrook is an RCVS & European Specialist in Veterinary Anaesthesia & Analgesia and is President of the Association of Veterinary Anaesthetists. Carl works at Anderson Moores Veterinary Specialists.
The intended audience for this pain update is veterinary professionals. This pain update is based on clinical experience and independent opinion.