• Xue-Ting Deng, Yuan Han, Wen-Tao Liu, and Xue-Jun Song.
• Research Center for Anesthesiology and Pain Medicine, and Department of Anesthesiology, Peking University Cancer Hospital & Institute, Beijing, China.
• Pain Med. 2017 Oct 1; 18 (10): 1961-1974.

ObjectivesOpiate analgesics are the most effective treatments for severe pain, but their clinical utility is often hampered by the development of analgesic tolerance. There are striking similarities between morphine actions and neuropathic pain. We have demonstrated that B vitamins can attenuate neuropathic pain after peripheral nerve injury, sensory neuron inflammation/compression, and transient spinal cord ischemia. Given this similarity, the present study investigated whether B vitamins might be able to modify the antinociceptive effect of morphine as well as morphine tolerance in mice.MethodsCell signaling was assayed by Western blot and immunohistochemistry. Antinociception was assessed in ICR mice using the tail flick. The effects of B vitamins on acute morphine-induced antinociception and chronic morphine tolerance were studied.Results1) Co-administration of B vitamins with morphine potentiates acute morphine antinociception. 2) B vitamins attenuate the development of antinociceptive tolerance to chronic morphine administration and inhibit morphine-induced p-NR1, p-PKC in the spinal cord. 3) Morphine induces microglial activation, as evidenced by increased p38 MAPK phosphorylation, IBA1, and IL-1β in the spinal cord, and these changes are inhibited by B vitamins. 4) Treatment of B vitamins alone shows no notable effects on pain threshold and activity of microglia invivo.ConclusionsB vitamins potentiate acute morphine antinociception and attenuate chronic morphine tolerance.© 2017 American Academy of Pain Medicine. All rights reserved. For permissions, please e-mail: journals.permissions@oup.com

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