Antioxidant-based pain killers may one day become a viable alternative to addictive medications such as morphine or NSAIDs, which are demonstrating serious side effects with long-term use.
Researchers found that antioxidants practically eradicated pain-like behavior in nearly three-quarters of mice with inflamed hind paws. Reactive oxygen species (ROS) have been implicated in contributing to and/or maintaining conditions of chronic pain. Recent pre-clinical reports suggest that antioxidants are effective analgesics in neuropathic and inflammatory pain models.
“When it comes to pain killers, there aren’t many choices between over-the-counter pain relievers like ibuprofen and aspirin and prescription opiates like morphine,” said Robert Stephens, a professor of physiology and cell biology at Ohio State University. He’s the lead author of a study examining the effects of antioxidants as pain killers.
“We need drugs that fall somewhere between these two extremes,” Stephens said. “Someone suffering from chronic pain can become dependent on, or even addicted to, heavy-duty pain killers like morphine.”
The study appears in October 2006 issue of the journal Behavioural Brain Research.
Antioxidants neutralize free radicals, substances that damage cells. While our bodies constantly produce free radicals, healthy tissues inactivate these damaging substances and keep their levels in check. It’s when free-radical production somehow exceeds the body’s natural defenses that problems occur. Researchers have linked this excessive production to diseases like cancer and Alzheimer’s.
A handful of studies published in the last 10 years suggest that free radicals may also contribute to chronic pain. Left unchecked, free radicals build up in the body and can further damage already-injured tissue. An equally small number of studies, including those by Stephens, suggest that antioxidants may fight chronic pain by helping the body to break down free radicals.
“Studying the pain-killing effects of antioxidants is an emerging area of research,” Stephens said. “The FDA hasn’t approved antioxidants for the treatment of chronic pain. But down the road we may see some drugs that contain antioxidants.”
Stephens and his colleagues first injected one of three different antioxidants into mice. An additional group of control mice received only saline. The antioxidants used in this study – PBN (phenyl-N-tert-butylnitrone), TEMPOL (4-hydroxy-2,2,6,6-tetramethylpiperidine-1-oxy) and NAC (N-acetyl-L-cysteine) – aren’t the same as those found in fruits and vegetables, and two, which are synthetic, PBM and TEMPOL, are currently only available for scientific purposes. NAC is available as a dietary supplement.
“Right now we’re trying to show that antioxidants are viable pain killers,” Stephens said. “Similar work by other researchers suggested that these antioxidants were the best available. And while certain foods likely contain pain-killing antioxidants, these agents have not been systematically tested as pain relievers.”
Dr Stephens' team injected mice with the synthetic antioxidant PBN, another synthetic antioxidant TEMPOL, NAC (N-acetyl-L-cysteine), or saline as a placebo prior to injecting the left hind paw with an irritant that causes inflammation and discomfort. The subsequent observation period was divided into a 5 minute acute phase during when the body first senses and reacts to pain, a 5 to 15 minute period of relative stillness in which the body utilizes its own mechanisms to inhibit pain, and a 15 to 30 minute tonic phase, during which the animals again show pain-like behavior by licking the irritated paw. They found that the three antioxidants were associated with a 70 to 90 percent reduction in pain-related behavior during the acute phase and a 78 to 98 percent decrease during the tonic phase compared to the control animals.
“We were surprised to see such a major decrease in pain in the mice, particularly during the acute phase,” Stephens said. “The antioxidants seem to preempt pain-like behavior. “Other investigators have given antioxidants to rodents after experimentally inducing pain and have found that the supplements relieve pain to a similar extent.”
A. Hacimuftuoglu, C.R. Handy, V.M. Goettl, C.G. Lin, S. Dane and R.L. Stephens, Jr. Antioxidants attenuate multiple phases of formalin-induced nociceptive response in mice. Behavioural Brain Research; Volume 173, Issue 2 , 16 October 2006, Pages 211-216.