July 29, 2011 — The controversial diabetes drug rosiglitazone (Avandia, GlaxoSmithKline), which some experts wanted to banish and others preferred to keep but with tight restrictions, is now being explored as a pain medication.
"We might be able to prevent the development of nerve damage–induced neuropathic pain by controlling peripheral acute inflammation as soon as possible," coauthor Maiko Hasegawa-Moriyama, MD, from the Juntendo University School of Medicine in Tokyo, Japan, told Medscape Medical News.
"The numerous studies concerning diabetes and chronic inflammation in adipose tissue and in blood vessels have demonstrated that peroxisome proliferator-activated receptor (PPAR) gamma agonists promote a phenotype switch of macrophages from proinflammatory to tissue protective state, resulting in the improvement of insulin resistance and atherosclerosis," Dr. Hasegawa-Moriyama explained. "Likewise, regulating the properties of macrophages by PPAR gamma agonist in the acute phase might prevent inflammation-induced chronic pain."
The study will be published in the August issue of Anesthesia and Analgesia but was released early online.
The preliminary exploration is based on a mouse model, and Dr. Hasegawa-Moriyama says his team was surprised by what it found. "Only 3-day administration of rosiglitazone immediately after nerve injury was sufficient to inhibit the development of chronic pain," he said.
Cardiovascular Risk
In patients who take rosiglitazone for glucose control, there is abundant evidence that rosiglitazone can increase the risk for heart failure, myocardial infarction, or death compared with its cousin pioglitazone (Actos, Takeda). But certain patients can take it successfully, and for others it may be a last best bet among antidiabetic agents, some argue.
The US Food and Drug Administration (FDA) recently released a rosiglitazone risk management strategy. The new document limits the drug to patients already successfully treated with it or those for whom it's a last resort to control blood glucose medically.
"Healthcare providers and patients must be enrolled in the Avandia-Rosiglitazone Medicines Access Program in order to prescribe and receive rosiglitazone medicines," the FDA statement says.
It requires that providers who want to prescribe rosiglitazone, as well as pharmacies that distribute the drug, be specially trained and certified for the purpose.
The European Medicines Agency went further than its US counterpart last year by putting a complete halt on the sale of medications that contain rosiglitazone.
For Inflammatory, Not Chronic State
Dr. Hasegawa-Moriyama told Medscape Medical News that for pain management, patients would not need to take their medication daily like those with diabetes and might experience less risk because of it.
"We also demonstrated that local injection of rosiglitazone produced similar effects as systemic administration. The side effects on the cardiovascular system can be avoided by local administration and by limiting duration for treatment to the acute phase."
Still, the researchers found rosiglitazone did not improve tactile allodynia once neuropathic pain was established. "This means PPAR gamma agonist is effective in the inflammatory state but not the chronic state," Dr. Hasegawa-Moriyama said.
The researchers have disclosed no relevant financial relationships.
Anesth Analg. 2011;113:398-404.
Medscape Medical News © 2011 WebMD, LLC
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Cite this: Rosiglitazone Investigated for Neuropathic Pain - Medscape - Jul 29, 2011.
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