Resveratrol Preserves Response to Morphine

Emma Hitt, PhD

November 20, 2012

Resveratrol, a polyphenol found in red wine, also may have an ability to preserve the pain-relieving effect of morphine in rats that are morphine tolerant, a study suggests.

Their work "provides new evidence that resveratrol has potential as an analgesic adjuvant in clinical pain management, particularly for patients who need long-term morphine administration and for morphine-tolerant patients who require better pain relief," the researchers, led by Chih-Shung Wong, MD, and colleagues from Cathay General Hospital, Taipei, Taiwan, conclude.

The results were published in the October issue of Anesthesia & Analgesia, the official journal of the International Anesthesia Research Society (IARS).

Antioxidant and Antiinflammatory

According to the researchers, morphine tolerance includes opioid receptor uncoupling and endocytosis/desensitization, increased binding of β-arrestin to the opioid receptor, glutamatergic receptor activation, and neuroinflammation.

Resveratrol is found in many plant-based foods, including the skin of grapes, and is thought, on the basis of the findings of many studies, to have antioxidant and antiinflammatory effects as well as protective effects on the nervous system.

Dr. Wong and colleagues induced morphine tolerance in rats and then tested whether resveratrol significantly enhanced the effects of morphine.

They found that the pain-relieving response to morphine was only about 20% of normal in the morphine-tolerant rats, whereas in similar rats receiving resveratrol, morphine responses were restored to about 60% of normal.

A potential mechanism of action for resveratrol for improving the morphine response is that long-term morphine infusion upregulated expression of protein subunits of the N-methyl-D-aspartate receptor (NMDAR), Dr. Wong and colleagues speculate.

"Emerging evidence suggests that NMDAR activation has a crucial role in morphine tolerance, and blockade of NMDAR function effectively attenuates morphine tolerance," they note. Resveratrol also blocked the expression of cytokines, potentially decreasing the neuro-inflammatory response in rats with morphine tolerance.

The study was supported by a grant from the National Science Council and the Cathay General Hospital, Taipei, Taiwan. The authors have disclosed no relevant financial relationships.

Anesth Analg. 2012;115:944-952. Abstract