A blocking antibody to nerve growth factor attenuates skeletal pain induced by prostate tumor cells growing in bone

被引:192
作者
Halvorson, KG
Kubota, K
Sevcik, MA
Lindsay, TH
Sotillo, JE
Ghilardi, JR
Rosol, TJ
Boustany, L
Shelton, DL
Mantyh, PW
机构
[1] Univ Minnesota, Dept Diagnost & Biol Sci, Minneapolis, MN 55455 USA
[2] Univ Minnesota, Neurosyst Ctr, Minneapolis, MN 55455 USA
[3] Univ Minnesota, Dept Psychiat, Minneapolis, MN 55455 USA
[4] Univ Minnesota, Dept Neurosci, Minneapolis, MN 55455 USA
[5] Univ Minnesota, Ctr Canc, Minneapolis, MN 55455 USA
[6] Vet Affairs Med Ctr, Res Serv, Minneapolis, MN 55417 USA
[7] Ohio State Univ, Coll Vet Med, Columbus, OH 43210 USA
[8] Ohio State Univ, Res Off, Columbus, OH 43210 USA
[9] Rinat Neurosci Corp, Palo Alto, CA USA
关键词
D O I
10.1158/0008-5472.CAN-05-0826
中图分类号
R73 [肿瘤学];
学科分类号
100214 [肿瘤学];
摘要
Prostate cancer is unique in that bone is often the only clinically detectable site of metastasis. Prostate tumors that have metastasized to bone frequently induce bone pain which can be difficult to fully control as it seems to be driven simultaneously by inflammatory, neuropathic, and tumorigenic mechanisms. As nerve growth factor (NGF) has been shown to modulate inflammatory and some neuropathic pain states in animal models, an NGF-sequestering antibody was administered in a prostate model of bone cancer where significant bone formation and bone destruction occur simultaneously in the mouse femur. Administration of a blocking antibody to NGF produced a significant reduction in both early and late stage bone cancer pain-related behaviors that was greater than or equivalent to that achieved with acute administration of 10 or 30 mg/kg of morphine sulfate. In contrast, this therapy did not influence tumor-induced bone remodeling, osteoblast proliferation, osteoclastogenesis, tumor growth, or markers of sensory or sympathetic innervation in the skin or bone. One rather unique aspect of the sensory innervation of bone, that may partially explain the analgesic efficacy of anti-NGF therapy in relieving prostate cancer-induced bone pain, is that nearly all nerve fibers that innervate the bone express trkA and p75, and these are the receptors through which NGF sensitizes and/or activates nociceptors. The present results suggest that anti-NGF therapy may be effective in reducing pain and enhancing the quality of life in patients with prostate tumor-induced bone cancer pain.
引用
收藏
页码:9426 / 9435
页数:10
相关论文
共 61 条
[1]
PERIPHERAL ADMINISTRATION OF NERVE GROWTH-FACTOR IN THE ADULT-RAT PRODUCES A THERMAL HYPERALGESIA THAT REQUIRES THE PRESENCE OF SYMPATHETIC POSTGANGLIONIC NEURONS [J].
ANDREEV, NY ;
DIMITRIEVA, N ;
KOLTZENBURG, M ;
MCMAHON, SB .
PAIN, 1995, 63 (01) :109-115
[2]
[Anonymous], 2000, BONE DIS MACROSCOPIC
[3]
NGF and GDNF ameliorate the increase in ATF3 expression which occurs in dorsal root ganglion cells in response to peripheral nerve injury [J].
Averill, S ;
Michael, GJ ;
Shortland, PJ ;
Leavesley, RC ;
King, VR ;
Bradbury, EJ ;
McMahon, SB ;
Priestley, JV .
EUROPEAN JOURNAL OF NEUROSCIENCE, 2004, 19 (06) :1437-1445
[4]
IMMUNOCYTOCHEMICAL LOCALIZATION OF TRKA RECEPTORS IN CHEMICALLY IDENTIFIED SUBGROUPS OF ADULT-RAT SENSORY NEURONS [J].
AVERILL, S ;
MCMAHON, SB ;
CLARY, DO ;
REICHARDT, LF ;
PRIESTLEY, JV .
EUROPEAN JOURNAL OF NEUROSCIENCE, 1995, 7 (07) :1484-1494
[5]
Nerve growth factor evokes hyperalgesia in mice lacking the low-affinity neurotrophin receptor p75 [J].
Bergmann, I ;
Reiter, R ;
Toyka, KV ;
Koltzenburg, M .
NEUROSCIENCE LETTERS, 1998, 255 (02) :87-90
[6]
Incidence of skeletal complications in patients with bone metastatic prostate cancer and hormone refractory disease: Predictive role of bone resorption and formation markers evaluated at baseline [J].
Berruti, A ;
Dogliotti, L ;
Bitossi, R ;
Fasolis, G ;
Gorzegno, G ;
Bellina, M ;
Torta, M ;
Porpiglia, F ;
Fontana, D ;
Angeli, A .
JOURNAL OF UROLOGY, 2000, 164 (04) :1248-1253
[7]
SUBSTANCE-P-IMMUNOREACTIVE AND CGRP-IMMUNOREACTIVE NERVES IN BONE [J].
BJURHOLM, A ;
KREICBERGS, A ;
BRODIN, E ;
SCHULTZBERG, M .
PEPTIDES, 1988, 9 (01) :165-171
[8]
BODY JJ, 2000, TUMOR BONE DIS OSTEO, P561
[9]
QUANTITATIVE ASSESSMENT OF TACTILE ALLODYNIA IN THE RAT PAW [J].
CHAPLAN, SR ;
BACH, FW ;
POGREL, JW ;
CHUNG, JM ;
YAKSH, TL .
JOURNAL OF NEUROSCIENCE METHODS, 1994, 53 (01) :55-63
[10]
Bone cancer pain [J].
Clohisy, DR ;
Mantyh, PW .
CANCER, 2003, 97 (03) :866-873