A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

Alysia N. Lozano-Ondoua, Courtney Wright, Anna Vardanyan, Tamara King, Tally M. Largent-Milnes, Mark A Nelson, Juan Miguel Jimenez-Andrade, Patrick W Mantyh, Todd W Vanderah

Research output: Contribution to journalArticle

55 Citations (Scopus)

Abstract

Aims: Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main methods: A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key findings: Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7. days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance: These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.

Original languageEnglish (US)
Pages (from-to)646-653
Number of pages8
JournalLife Sciences
Volume86
Issue number17-18
DOIs
StatePublished - Apr 2010

Fingerprint

Cannabinoid Receptor Agonists
Bone Neoplasms
Cannabinoids
Bone
Opiate Alkaloids
Bone and Bones
Femur
Pain
Bone Fractures
Sarcoma
Extremities
Catalepsy
Cancer Pain
Touch
Neuralgia
Tumors
Hypothermia
Bearings (structural)
Osteoporosis
Analgesics

Keywords

  • AM1241
  • Bone cancer pain
  • CB agonists
  • Osteolytic sarcoma

ASJC Scopus subject areas

  • Pharmacology, Toxicology and Pharmaceutics(all)
  • Biochemistry, Genetics and Molecular Biology(all)

Cite this

A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. / Lozano-Ondoua, Alysia N.; Wright, Courtney; Vardanyan, Anna; King, Tamara; Largent-Milnes, Tally M.; Nelson, Mark A; Jimenez-Andrade, Juan Miguel; Mantyh, Patrick W; Vanderah, Todd W.

In: Life Sciences, Vol. 86, No. 17-18, 04.2010, p. 646-653.

Research output: Contribution to journalArticle

Lozano-Ondoua, AN, Wright, C, Vardanyan, A, King, T, Largent-Milnes, TM, Nelson, MA, Jimenez-Andrade, JM, Mantyh, PW & Vanderah, TW 2010, 'A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss', Life Sciences, vol. 86, no. 17-18, pp. 646-653. https://doi.org/10.1016/j.lfs.2010.02.014
Lozano-Ondoua AN, Wright C, Vardanyan A, King T, Largent-Milnes TM, Nelson MA et al. A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. Life Sciences. 2010 Apr;86(17-18):646-653. https://doi.org/10.1016/j.lfs.2010.02.014
Lozano-Ondoua, Alysia N. ; Wright, Courtney ; Vardanyan, Anna ; King, Tamara ; Largent-Milnes, Tally M. ; Nelson, Mark A ; Jimenez-Andrade, Juan Miguel ; Mantyh, Patrick W ; Vanderah, Todd W. / A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss. In: Life Sciences. 2010 ; Vol. 86, No. 17-18. pp. 646-653.
@article{229bf083b63c4833a7f90451e05a19f3,
title = "A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss",
abstract = "Aims: Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main methods: A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key findings: Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7. days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance: These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.",
keywords = "AM1241, Bone cancer pain, CB agonists, Osteolytic sarcoma",
author = "Lozano-Ondoua, {Alysia N.} and Courtney Wright and Anna Vardanyan and Tamara King and Largent-Milnes, {Tally M.} and Nelson, {Mark A} and Jimenez-Andrade, {Juan Miguel} and Mantyh, {Patrick W} and Vanderah, {Todd W}",
year = "2010",
month = "4",
doi = "10.1016/j.lfs.2010.02.014",
language = "English (US)",
volume = "86",
pages = "646--653",
journal = "Life Sciences",
issn = "0024-3205",
publisher = "Elsevier Inc.",
number = "17-18",

}

TY - JOUR

T1 - A cannabinoid 2 receptor agonist attenuates bone cancer-induced pain and bone loss

AU - Lozano-Ondoua, Alysia N.

AU - Wright, Courtney

AU - Vardanyan, Anna

AU - King, Tamara

AU - Largent-Milnes, Tally M.

AU - Nelson, Mark A

AU - Jimenez-Andrade, Juan Miguel

AU - Mantyh, Patrick W

AU - Vanderah, Todd W

PY - 2010/4

Y1 - 2010/4

N2 - Aims: Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main methods: A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key findings: Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7. days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance: These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.

AB - Aims: Cannabinoid CB2 agonists have been shown to alleviate behavioral signs of inflammatory and neuropathic pain in animal models. AM1241, a CB2 agonist, does not demonstrate central nervous system side effects seen with CB1 agonists such as hypothermia and catalepsy. Metastatic bone cancer causes severe pain in patients and is treated with analgesics such as opiates. Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB2 selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB2 agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation. Main methods: A murine bone cancer model was used in which osteolytic sarcoma cells were injected into the intramedullary space of the distal end of the femur. Behavioral and radiographic image analysis was performed at days 7, 10 and 14 after injection of tumor cells into the femur. Key findings: Osteolytic sarcoma within the femur produced spontaneous and touch evoked behavioral signs of pain within the tumor-bearing limb. The systemic administration of AM1241 acutely or for 7. days significantly attenuated spontaneous and evoked pain in the inoculated limb. Sustained AM1241 significantly reduced bone loss and decreased the incidence of cancer-induced bone fractures. Significance: These findings suggest a novel therapy for cancer-induced bone pain, bone loss and bone fracture while lacking many unwanted side effects seen with current treatments for bone cancer pain.

KW - AM1241

KW - Bone cancer pain

KW - CB agonists

KW - Osteolytic sarcoma

UR - http://www.scopus.com/inward/record.url?scp=77951238358&partnerID=8YFLogxK

UR - http://www.scopus.com/inward/citedby.url?scp=77951238358&partnerID=8YFLogxK

U2 - 10.1016/j.lfs.2010.02.014

DO - 10.1016/j.lfs.2010.02.014

M3 - Article

C2 - 20176037

AN - SCOPUS:77951238358

VL - 86

SP - 646

EP - 653

JO - Life Sciences

JF - Life Sciences

SN - 0024-3205

IS - 17-18

ER -