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Chronic Pain Relief Improved by Resveratrol Alongside Morphine

resveratrol aids morphine effects reduces morphine tolerance for chronic back pain relief

Taking pain medications with wine is not advised but a resveratrol supplement may help avoid morphine tolerance.

Treating chronic back pain with morphine usually avoided as patients build a tolerance to the drug and are at risk of side-effects, addiction and overdose as dosage increases. New research suggests, however, that resveratrol may preserve the pain-relief benefit of morphine, allowing patients with spinal stenosis, or other cause of chronic pain, to continue using morphine effectively at a reduced dose.

What is Resveratrol?

Resveratrol is a polyphenol found in red wine and often touted as the answer to the French Paradox of a rich diet and good cardiovascular health. This substance, present in the skin of red grapes and a number of other foods, is a powerful antioxidant often sold in supplement form but researchers in Taipei, Taiwan, have now found another benefit of resveratrol: improved pain relief.

New Research into Pain Relief

The study looked at rats that are morphine tolerant and discovered 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.” Lead researcher, Chih-Shung Wong, MD, and colleagues from Cathay General Hospital, published their work in Anesthesia & Analgesia’s October issue, with a suggestion for the possible mechanism by which resveratrol helps.

What is Morphine Tolerance?

Morphine tolerance occurs in part because of opioid receptor uncoupling, cellular death or desensitization, nerve inflammation, glutamatergic receptor activation and increased opioid receptor binding of Beta-arrestin. Resveratrol is not only thought to act as an anti-inflammatory substance and antioxidant but the researchers also suggest that it upregulates expression of protein subunits of the N-methyl-D-aspartate receptor (NMDAR) which is thought to be significant in morphine tolerance. Blocking NMDAR function effectively weakens tolerance to morphine so this effect of resveratrol increases morphine’s analgesic properties..

Restoring Pain Relieving Effect of Morphine

Wong, et al, caused a population of Wistar rats to become morphine tolerant, with pain-relieving response measured at around 20% of normal when a tail-flick test to cause pain was carried out. They then measured pain response in rats given resveratrol and noted a restoration to around 60% of normal. The study was placebo controlled, and the rats underwent the pain-inducing tail-flick test every thirty minutes for 120 minutes after receiving either resveratrol or saline.

How Resveratrol Aids Pain Relief

Blocking of pro-inflammatory cytokines may be one aspect of this effect of resveratrol, thereby lowering nerve inflammation and reducing pain overall. In the morphine tolerant rats, chronic morphine use was found to activate glial cells and increase pro-inflammatory cytokine tumor necrosis factor-alpa, interleukin-1Beta, and interleukin-6 mRNA expression in the spinal cord. Rats given resveratrol before the morphine challenge had such effects suppressed.

Chronic Back Pain Relief

Patients with chronic spinal stenosis who are ineligible for back surgery or who have failed to achieve pain relief with surgery and conservative treatment options may be prescribed long-term opioid pain relief medications. Many such patients fear the development of morphine tolerance because this is often seen as the last option for relieving long-term back pain from an untreatable condition. News that a substance found in red grapes, resveratrol, may preserve morphine’s pain relieving effects is certainly welcome, although it should be stressed that taking analgesics with red wine is not recommended.


Tsai, Ru-Yin, Chou, Kuang-Yi, et al, (2012), Resveratrol Regulates N-Methyl-d-Aspartate Receptor Expression and Suppresses Neuroinflammation in Morphine-Tolerant Rats, Anesth Analg. 2012;115:944-952.

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