To explore the effects of cannabinoid 2 receptor (CB2) in the development of bone cancer pain in mice.”
The cannabinoid 2 receptor plays an important role in the formation of bone cancer pain.”
“Metastatic and primary bone cancers are usually accompanied by severe pain that is difficult to manage. In light of the adverse side effects of opioids, manipulation of the endocannabinoid system may provide an effective alternative for the treatment of cancer pain…
These data extend our previous findings with anandamide in the same model and suggest that the peripheral endocannabinoid system is a promising target for the management of cancer pain.
Taken together, the data demonstrate that peripheral 2-AG signaling may be a significant target to exploit for the management of cancer pain. In contrast to AEA, which inhibits nociception through CB1 receptors… Dual pharmacological modulation of peripheral AEA and 2-AG signaling that directly and indirectly affects DRG neurons may be a novel approach to reducing cancer pain without the side effects…”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC3104059/
“…a great body of evidence demonstrates the analgesic efficacy of systemically administered CB2 agonists in acute and chronic experimental pain….
The activation of CB2 receptors induces analgesia in experimental models of chronic pain. The present experiments were designed to study whether the activation of peripheral or spinal CB2 receptors relieves thermal hyperalgesia and mechanical allodynia in two models of bone cancer pain.
Spinal CB2 receptors are involved in the antiallodynic effect… in two neoplastic models while peripheral and spinal receptors participate in the antihyperalgesic effects… The use of drugs that activate CB2 receptors could be a useful strategy to counteract bone cancer-induced pain symptoms.”
“CB2 agonists not only produce antinociceptive and anti-inflammatory effects, but also have been shown to increase bone density.”
“Recent reports suggest that sustained opiates can produce paradoxical hyperalgesic actions and enhance bone destruction in a murine model of bone cancer. In contrast, CB(2) selective agonists have been shown to reduce bone loss associated with a model of osteoporosis. Here we tested whether a CB(2) agonist administered over a 7day period inhibits bone cancer-induced pain as well as attenuates cancer-induced bone degradation.”
“Based on the antihyperalgesic effects of CB2 agonists, the lack of potential CNS-induced side effects and their propensity to stimulated bone growth, we addressed whether the sustained selective CB2 agonists… has the potential to alleviate bone cancer-induced pain while maintaining bone integrity in a murine model of bone cancer”.
“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.”
http://www.ncbi.nlm.nih.gov/pmc/articles/PMC2871326/
“Most commonly originating from breast malignancies, metastatic bone cancer causes bone destruction and severe pain. Although novel chemotherapeutic agents have increased life expectancy, patients are experiencing higher incidences of fracture, pain, and drug-induced side effects; furthermore, recent findings suggest that patients are severely under-treated for their cancer pain. Strong analgesics, namely opiates, are first-line therapy in alleviating cancer-related pain despite the severe side effects, including enhanced bone destruction with sustained administration.Bone resorption is primarily treated with bisphosphonates, which are associated with highly undesirable side-effects including nephrotoxicity and osteonecrosis of the jaw.In contrast, cannabinoid CB(2) receptor-specific agonists have been shown to reduce bone loss and stimulate bone formation in a model of osteoporosis.CB(2) agonists produce analgesia in both inflammatory and neuropathic pain models. Notably, mixed CB(1) /CB(2) agonists also demonstrate a reduction in ErbB2-driven breast cancer progression. Here we demonstrate for the first time that CB(2) agonists reduce breast cancer-induced bone pain, bone loss and breast cancer proliferation via cytokine/chemokine suppression.Studies utilized the spontaneously-occurring murine mammary cell line (66.1) implanted into the femur intramedullary space; measurements of spontaneous pain, bone loss and cancer proliferation were made. The systemic administration of a CB(2) agonist, JWH015, for seven days significantly attenuated bone remodeling, assuaged spontaneous pain and decreased primary tumor burden. CB(2) -mediated effects in vivo were reversed by concurrent treatment with a CB(2) antagonist/inverse agonist but not with a CB(1) antagonist/inverse agonist. In vitro, JWH015 reduced cancer cell proliferation and inflammatory mediators that have been shown to promote pain, bone loss and proliferation.Taken together, these results suggest CB(2) agonists as a novel treatment for breast cancer-induced bone pain, where disease modifications include a reduction in bone loss, suppression of cancer growth, attenuation of severe bone-pain and increased survival without the major side effects of current therapeutic options.”
“The endocannabinoid system is implicated in a variety of physiological and pathological conditions (inflammation, immunomodulation, analgesia, cancer and others).
The main active ingredient of cannabis, Δ(9) -tetrahydrocannabinol (Δ(9) -THC), produces its effects through activation of CB(1) and CB(2) receptors. CB(1) receptors are expressed at high levels in the central nervous system (CNS), whereas CB(2) receptors are concentrated predominantly, although not exclusively, in cells of the immune system.
Endocannabinoids are endogenous lipid-signalling molecules that are generated in the cell membrane from phospholipid precursors. The two best characterized endocannabinoids identified to date are anandamide (AEA) and 2-arachidonoylglycerol (2-AG). Here we review the relationship between the endocannabinoid system and anti-tumour actions (inhibition of cell proliferation and migration, induction of apoptosis, reduction of tumour growth) of the cannabinoids in different types of cancer.
This review will focus on examining how activation of the endocannabinoid system impacts breast, prostate and bone cancers in both in vitro and in vivo systems. The therapeutic potential of cannabinoids for cancer, as identified in clinical trials, is also discussed.
Identification of safe and effective treatments to manage and improve cancer therapy is critical to improve quality of life and reduce unnecessary suffering in cancer patients. In this regard, cannabis-like compounds offer therapeutic potential for the treatment of breast, prostate and bone cancer in patients.
Further basic research on anti-cancer properties of cannabinoids as well as clinical trials of cannabinoid therapeutic efficacy in breast, prostate and bone cancer is therefore warranted.” http://www.ncbi.nlm.nih.gov/pubmed/21410463
“The available literature suggests that the endocannabinoid system may be targeted to suppress the evolution and progression of breast, prostate and bone cancer as well as the accompanying pain syndromes. Many in vitro and in vivo studies have shown that cannabinoids are efficacious in reducing cancer progression (i.e. inhibition of tumour growth and metastases as well as induction of apoptosis and other anti-cancer properties) in breast, prostate and bone cancer. Although this review focuses on these three types of cancer, activation of the endocannabinoid signalling system produces anti-cancer effects in other types of cancer.” http://onlinelibrary.wiley.com/doi/10.1111/j.1476-5381.2011.01327.x/full