Anti-NGF therapy profoundly reduces bone cancer pain and the accompanying increase in markers of peripheral and central sensitization

• Published in: Pain (Amsterdam) Vol. 115; no. 1; pp. 128 - 141
• Main Authors: Sevcik, Molly A., Ghilardi, Joseph R., Peters, Christopher M., Lindsay, Theodore H., Halvorson, Kyle G., Jonas, Beth M., Kubota, Kazufumi, Kuskowski, Michael A., Boustany, Leila, Shelton, David L., Mantyh, Patrick W.
• Format: Journal Article
• Language: English
• Published: Amsterdam Elsevier B.V 01.05.2005; Elsevier
• Subjects: Analgesics; Animals; Antibodies, Monoclonal - administration & dosage; Biological and medical sciences; Biomarkers - metabolism; Cranial nerves. Spinal roots. Peripheral nerves. Autonomic nervous system. Gustation. Olfaction; Diseases of the osteoarticular system; Femoral Neoplasms - complications; Femoral Neoplasms - diagnosis; Femoral Neoplasms - drug therapy; Male; Medical sciences; Metastasis; Mice; Mice, Inbred C3H; Nerve Growth Factor - immunology; Nervous system (semeiology, syndromes); Neurology; Neuropharmacology; NGF; Nociception; Nociceptors - drug effects; Nociceptors - metabolism; Pain - diagnosis; Pain - etiology; Pain - prevention & control; Peripheral Nerves - drug effects; Peripheral Nerves - metabolism; Pharmacology. Drug treatments; Sarcoma - complications; Sarcoma - diagnosis; Sarcoma - drug therapy; Skeletal malignancies; Spinal Cord - drug effects; Spinal Cord - metabolism; Treatment Outcome; Tumor; Tumor Cells, Cultured; Tumors of striated muscle and skeleton; Nociception; Tumor; Metastasis; Skeletal malignancies; NGF; Animal model; Spinal cord; Innervation; Central nervous system; Nerve growth factor; Morphine; Peripheral neuropathy; Signal transduction; Nociceptor; Pain; Sensitization; Peripheral nerve disease; Behavior; Nervous system diseases; Antibody; Rodentia; Analgesia; Vertebrata; Mammalia; Treatment; Mouse; Animal; Spinal ganglion
• ISSN: 0304-3959; 1872-6623
• DOI: 10.1016/j.pain.2005.02.022

Bone cancer pain can be difficult to control, as it appears to be driven simultaneously by inflammatory, neuropathic and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and neuropathic pain states, we focused on a novel NGF sequestering antibody and demonstrated that two administrations of this therapy in a mouse model of bone cancer pain produces a profound reduction in both ongoing and movement-evoked bone cancer pain-related behaviors that was greater than that achieved with acute administration of 10 or 30 mg/kg of morphine. This therapy also reduced several neurochemical changes associated with peripheral and central sensitization in the dorsal root ganglion and spinal cord, whereas the therapy did not influence disease progression or markers of sensory or sympathetic innervation in the skin or bone. Mechanistically, the great majority of sensory fibers that innervate the bone are CGRP/TrkA expressing fibers, and if the sensitization and activation of these fibers is blocked by anti-NGF therapy there would not be another population of nociceptors, such as the non-peptidergic IB4/RET-IR nerve fibers, to take their place in signaling nociceptive events.