Virginia Thornley, Neurologist, Epileptologist
March 8, 2018
Chronic pain from neurological conditions such as neuropathic pain can become refractory to conventional medications. Interest is directed towards novel ways of treatment such as cannabidiol and THC which are known in animal models to be anti-inflammatory, analgesic and neuroprotective. Cannabinoids are being used more commonly in patients who have failed medical treatments and remain a viable option in the treatment of pain. Many animal models point towards mechanistic evidence that cannabidiol and THC reduce severity and frequency of pain syndromes. Cannabidiol is non-intoxicating and is an alternative form of management. With THC, the level of pain relief is higher but with that comes a higher risk of side effects at greater doses.
Cannabidiol and neuropathic pain in joints
Osteoarthritis involves inflammation, pain, and neuropathic pain. Cannabidiol was studied in rat models and its effect on pain from the joints and nerves. In end-stage osteoarthritis, cannabidiol reduced joint afferent pain. Transient joint inflammation was reduced using cannabidiol. CBD application used prophylactically demonstrated lack of development of pain and inflammation during later stages.
One study suggests that chronic neuropathic pain might be suppressed by cannabidiol through alpha 3 glycine receptors. In mice lacking these receptors, there is no cannabidiol analgesic effect. Cannabinoids are found to support glycine activity in the dorsal cell neurons in rats. This suggests that glycinergic cannabinoids may provide a potential therapeutic option in treating neuropathic pain. There is lack of psychoactive side effects or development of tolerance (1).
Cannabidiol and neuropathic pain studies
In one review of 15 randomized controlled trials against placebo with a total of 1619 patients, 13 studies consisting of 1565 patients reported a reduction of pain compared to placebo which was statistically significant. There was a frequency reduction in pain of 30%. 10 studies used nasal tetrahydrocannabinol /cannabidiol and 3 used synthetic cannabidiol while 2 used medical cannabis. They concluded that cannabidiols were marginally superior and had greater side effects than placebo. It is a treatment option for patients who have failed several lines of treatment. Some flaws that can be seen in this study is that with this study, some centers used synthetic forms of cannabinoids and others used a combination of THC and cannabidiol. Synthetic medical marijuana has a different quality compared to a product that is purely organic and made from natural materials. High doses of THC is known to cause side effects while with lower doses of THC pain relief may be obtained with fewer side effects. It is not clear how pure the products are which were being administered.
In one large study of 303 patients with peripheral neuropathy, 128 used CBD/THC spray and 118 randomized to placebo. End-point was a 30% responder rate using the PNP numerical scale 0-10. There was a substantially higher number of responders for CBD:THC but not statistically significant. Quality of life and sleep improved in those with CBD/THC nasal spray. They concluded that use of CBD/THC helped improve pain from peripheral neuropathy and there were no substantial adverse effects from the patients studied (3).
- Xiong, et al, “Cannabinoids suppress inflammatory and neuropathic pain by targeting alpha 3 glycine receptors,” Journal of Experimental Medicine, 2012, Jun., 209(6):1121-1134.
- Petzke, et al, “Efficacy, tolerability, and safety of cannabinoids for chronic neuropathic pain: a systemic review of randomized controlled studies,” Schmerz, 2016, Feb., 30(1):62-88
- Serpell, et al, “A double-blind, randomized, placebo-controlled, parallel group study of THC/CBD spray in peripheral neuropathic pain treatment,” European Journal of Pain, 2014, Aug., 18(7):999-1012.
Virginia Thornley, M.D., Neurologist, Epileptologist
March 1, 2018
As more and more survivors of cancer grow in number, there is increasing interest in treatments for chemotherapy-induced toxicity. Chemotherapy-induced peripheral neuropathies are one of the most common neurotoxic side effects prevalent in cancer survivors. Attention is drawn to alternative treatments such as stem cell research as at times, this condition may be resistant to treatment with conventional agents.
Common chemotherapeutic agents that cause neuropathy
Some of the most common chemotherapeutic agents that cause peripheral neuropathy include vincristine, oxaliplatin, cisplatin, paclitaxel. The sites most prevalent with neurotoxic effects include the dorsal root ganglion, peripheral nerves, satellite cells and Schwann cells as well as glial cells in the spinal cord.
Some mechanisms that are proposed that cause neural damage include glutamate activation, increased intracellular oxygen changes, DNA damage, altered cell repair, alteration in ion channels, change in mitochondrial metabolism and MAP kinase activation.
Role of stem cell in chemotherapy-induced peripheral neuropathy and other novel treatment approaches
In chemotherapy for colon cancer, oxaliplatin can cause chemo-induced peripheral neuropathy in 50% of patients. In one study, pain relieving qualities of mesenchymal stem cells were studied. Rat adipose stem cells were applied to rats with chemotherapy-induced peripheral neuropathy in one animal model. An IV injection of rat adipose stem cell injected into the rate of neuropathy revealed a reduced hypersensitivity to the noxious effects. Repeated injections every 5 days produced the same results. VEGF was noted to be upregulated or vascular endothelial growth factor. When a monoclonal antibody used against this VEGF was applied there was reduced pain, suggesting a role of VEGF in pain. Adult adipose mesenchymal stem cell may represent a novel approach to alleviating pain from chemotherapy-induced peripheral neuropathy. This rat model also elucidated the role an antibody against VEGF can play in the treatment of peripheral neuropathy caused by chemotherapy.
Pain might also be influenced by increased gap junction coupling during chemotherapy. In one study, using a gap coupling blocker, the pain was alleviated in chemotherapy-induced peripheral neuropathy in mice producing an analgesic effect(3).
- Di Cesare, et al, “Adipose-derived stem cells decrease pain in a rat model of oxaliplatin-induced neuropathy: role of VEGF-A modulation,” Neuropharmacology, 2018, Mar., 15; 131:166-175.
- Carozzi, et al, “Chemotherapy-induced neuropathy: what do we know now?” Neuroscience Letter, 2015, Jun., 2(596):90-107.
- Warwick, et al, “The contribution of satellite glial cells to chemotherapy-induced neuropathic pain,” European Journal of Pain, 2013, Apr., 17(4):571-80.