Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats

Nicotinamide riboside, a form of vitamin B3 and NAD+ precursor, relieves the nociceptive and aversive dimensions of paclitaxel-induced peripheral neuropathy in female rats

Published in Journal of the International Association for the Study of Pain (PAIN).

Injury to sensory afferent nerves may contribute to the peripheral neuropathies that develop after administration of chemotherapeutic agents. Manipulations that increase levels of nicotinamide adenine dinucleotide (NAD+) can protect against neuronal injury. This study examined whether nicotinamide riboside (NR), a next-generation form of vitamin B3 and precursor of NAD+, diminishes hypersensitivity to touch and avoidance behaviors in a female rodent model of peripheral neuropathy (CIPN) induced by a common chemotherapy drug used to treat breast and ovarian cancer called, paclitaxel. Female Sprague-Dawley rats received three injections of 6.6 mg/kg paclitaxel over five days. Daily oral administration of 200 mg/kg NR beginning seven days before chemotherapy treatment and then continuing for another 24 days prevented the development of touch hypersensitivity and lessened avoidance behaviors. These effects were sustained two-weeks after wash out. The study results indicated that this dose of NR increased blood levels of NAD+ by 50%, did not interfere with the myelosuppressive effects of chemotherapy (a necessary response for successful cancer treatment), and did not produce adverse locomotor effects.

Treatment with 200 mg/kg NR for three weeks after chemotherapy reversed well-established hypersensitivity to touch in a subset of rats and also lessened avoidance behaviors. Pretreatment with a common CIPN therapy used today called, p.o. acetyl-L-carnitine (ALCAR), did not produce the same results.  These findings suggest that agents that increase NAD+ represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. As NR is a vitamin B3 precursor of NAD+ and a nutritional supplement, clinical tests of this hypothesis in humans may be accelerated.

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