Resveratrol -- the same natural polyphenol found in red wine -- preserves the potent pain-relieving effect of morphine in rats that have developed morphine tolerance, suggests a study in the October issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).
If the findings are confirmed in humans, resveratrol might become a useful addition to clinical pain management approaches -- especially in patients with chronic, severe pain who have become tolerant to the effects of morphine. The study was performed by Dr Chih-Shung Wong and colleagues of Cathay General Hospital, Taipei, Taiwan.
Resveratrol's Effects in Spinal Cord Affects Morphine Responses
The researchers designed experiments to evaluate whether and how resveratrol affects behavioral pain responses to morphine in morphine-tolerant rats. Morphine and related opioid drugs play an important role in the treatment of severe pain, including cancer pain and other chronic pain conditions. However, the development of tolerance -- requiring much higher doses for effective pain control -- is an important limiting factor on their use.
Resveratrol is a polyphenol compound found in many plant-based foods; its presence in the skins of grapes may contribute to the health benefits of red wine. Previous studies have shown several biological effects of resveratrol, including antioxidant and anti-inflammatory effects as well as protective effects on the nervous system.
After inducing morphine tolerance in rats, the researchers tested the animals' spinal cord responses to morphine, with or without resveratrol. The results showed significant enhancement of morphine's effects in animals receiving resveratrol. In morphine-tolerant rats, the pain-relieving response to morphine was about 20 percent of normal. In rats receiving resveratrol, morphine responses were restored to about 60 percent of normal.
In preserving the pain-relieving effects of morphine, resveratrol appeared to work in two ways. It reversed the increase in expression of a type of neurotransmitter (N-methyl D-aspartate, or NMDA) receptors associated with morphine tolerance. Resveratrol also blocked the increase of inflammation-promoting substances, called cytokines, in rats with morphine tolerance.
The results add to other recent experimental evidence suggesting that resveratrol can maintain the pain-relieving effect of morphine. It also adds new information on how that effect may occur -- specifically through resveratrol's effects on the NMDA receptors and neuroinflammatory responses.
More research will be needed to determine whether some form of resveratrol treatment could be useful 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 conclude.
- Ru-Yin Tsai, Kuang-Yi Chou, Ching-Hui Shen, Chih-Cheng Chien, Wei-Yuan Tsai, Ya-Ni Huang, Pao-Luh Tao, Yaoh-Shiang Lin, Chih-Shung Wong. Resveratrol Regulates N-Methyl-D-Aspartate Receptor Expression and Suppresses Neuroinflammation in Morphine-Tolerant Rats. Anesthesia & Analgesia, 2012; 115 (4): 944 DOI: 10.1213/ANE.0b013e31825da0fb
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