Abstract: Injury to sensory afferents 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 third form of vitamin B3 and precursor of NAD+, diminishes tactile hypersensitivity and place escape–avoidance behaviors in a rodent model of paclitaxel-induced peripheral neuropathy. Female Sprague-Dawley rats received 3 intravenous injections of 6.6 mg/kg paclitaxel over 5 days. Daily oral administration of 200 mg/kg NR beginning 7 days before paclitaxel treatment and continuing for another 24 days prevented the development of tactile hypersensitivity and blunted place escape–avoidance behaviors. These effects were sustained after a 2-week washout period. This dose of NR increased blood levels of NAD+ by 50%, did not interfere with the myelosuppressive effects of paclitaxel, and did not produce adverse locomotor effects. Treatment with 200 mg/kg NR for 3 weeks after paclitaxel reversed the well-established tactile hypersensitivity in a subset of rats and blunted escape–avoidance behaviors. Pretreatment with 100 mg/kg oral acetyl-L-carnitine (ALCAR) did not prevent paclitaxel-induced tactile hypersensitivity or blunt escape–avoidance behaviors. ALCAR by itself produced tactile hypersensitivity. These findings suggest that agents that increase NAD+, a critical cofactor for mitochondrial oxidative phosphorylation systems and cellular redox systems involved with fuel utilization and energy metabolism, represent a novel therapeutic approach for relief of chemotherapy-induced peripheral neuropathies. Because NR is a vitamin B3 precursor of NAD+ and a nutritional supplement, clinical tests of this hypothesis may be accelerated.
Nicotinamide riboside, a form of vitamin B3, relieves tactile hypersensitivity and the aversive component chemotherapy-induced peripheral neuropathy, a common side effect of standard cancer treatment.
Departments of aAnesthesia
cPharmacology, The University of Iowa, Iowa City, IA, USA
Corresponding author. Address: Department of Anesthesia, The University of Iowa, 200 Hawkins Drive 3000 Med Labs, Iowa City, IA 52242, USA. Tel.: 319-335-9595; fax: 319-384-4567. E-mail address: firstname.lastname@example.org (D. L. Hammond).
Sponsorships or competing interests that may be relevant to content are disclosed at the end of this article.
Received November 03, 2016
Received in revised form January 19, 2017
Accepted January 24, 2017