Use of Animal Models in Understanding Cancer-induced Bone Pain

Abstract

Many common cancers have a propensity to metastasize to bone. Although malignancies often go undetected in their native tissues, bone metastases produce excruciating pain that severely compromises patient quality of life. Cancer-induced bone pain (CIBP) is poorly managed with existing medications, and its multifaceted etiology remains to be fully elucidated. Novel analgesic targets arise as more is learned about this complex and distinct pain state. Over the past two decades, multiple animal models have been developed to study CIBP’s unique pathology and identify therapeutic targets. Here, we review animal models of CIBP and the mechanistic insights gained as these models evolve. Findings from immunocompromised and immunocompetent host systems are discussed separately to highlight the effect of model choice on outcome. Gaining an understanding of the unique neuromolecular profile of cancer pain through the use of appropriate animal models will aid in the development of more effective therapeutics for CIBP.

Transient receptor potential ankyrin 1 (TRPA1) plays a critical role in a mouse model of cancer pain

“…[12][13][14]19 However, to the best of our knowledge, this is the first study showing the involvement of TRPA1 in a model of cancer pain. In addition, whereas a role for oxidative stress in models of cancer pain has been previously proposed, 35,39,48 this is the first paper showing that increased oxidative stress sustains cancer pain via its ability to target TRPA1 in nociceptors.…”

“…Different animal models have recently been proposed for reproducing metastatic cancer‐related pain, including tumor cells injection in the bone or the plantar pad . Previous studies showed that subcutaneous injection in the hind paw of B16‐F10 melanoma cells induces mechanical and cold allodynia that can be assessed 14 days after cells inoculation .…”

“…Different animal models have recently been proposed for reproducing metastatic cancer-related pain, including tumor cells injection in the bone or the plantar pad. [36][37][38][39] Previous studies showed that subcutaneous injection in the hind paw of B16-F10 melanoma cells induces mechanical and cold allodynia that can be assessed 14 days after cells inoculation. 27,28,40 Although mechanical and thermal allodynia is a hallmark of cancer pain, in the present study, we made the additional and original observation that mice exhibited thigmotaxis behavior 14 days after B16-F10 cell inoculation, including a decrease in number of rearing events and time spent in the inner zone in the open field test.…”

Angiotensin-(1-7)/Mas receptor as an antinociceptive agent in cancer-induced bone pain

“…28,63 Although the bone is innervated by both sympathetic and nociceptive nerve fibers, many tumors of the bone in humans lack detectable nerve fibers within the tumor and adjacent peripheral bone. 31,42 Contributors to nociceptive signaling associated with CIBP include an acidic tumor environment and the secretion of growth factors, cytokines, and chemokines from the tumor and tumor-associated cells, as well as enhanced nerve sprouting in the local environment.…”

Upregulation of (C-X-C motif) Ligand 13 (CXCL13) Attenuates Morphine Analgesia in Rats with Cancer-Induced Bone Pain

“…About 75–90% of patients with metastatic or advanced-stage cancer will suffer metastatic cancer-induced bone pain (CIBP), and the severity of CIBP is closely correlated with the extent of bone destruction [1–3]. CIBP is commonly induced by primary bone cancer or secondary bone metastasis from other malignancies, such as breast, prostate, and lung cancer, which may produce excruciating bone pain [4–6]. Generally, the primary treatment of CIBP is utilization of opioids and other adjuvants, such as morphine, nonsteroidal anti-inflammatory drugs, and cannabinoids [7].…”