Does Avandia (rosiglitazone) Signify a Neuropathy Breakthrough?

Thanks to studies and research from the University of Tokio, the diabetes drug, Avandia (rosiglitazone) is being hailed as a possible new drug for the treatment of neuropathy but like so many other drugs, it's not without its side effects and possible dangers. This scientific article from medmerits.com (see link below) discusses how it works and why it's being promoted as a possible breakthrough.
Unfortunately, from studies of diabetics, it has been found that Avandia can trigger fluid retention and congestive heart failure in certain patients, due to an unwanted effects on kidney function.
Avandia has been particularly controversial since 2007. A growing body of evidence suggests Avandia may increase the risk of heart disease and death, compared to other types of diabetes medications. The studies are not definitive, but given the lack of any significant advantage of Avandia over alternatives, few doctors see any reason to prescribe Avandia any more.
So where does that leave us? Are long-suffering HIV-patients going to be guinea pigs again and be exposed to unnecessary risks? One would assume that all necessary trials and tests will be carried out but it's always worth knowing the facts behind a drug before using it. It seems wise in this case to keep an eye out for any further news about Avandia.

Diabetes drug may help prevent neuropathic pain
July 26, 2011

The diabetes drug rosiglitazone (Avandia) can control inflammation leading to nerve damage and abnormal pain responses, suggests a paper in the August issue of Anesthesia & Analgesia, official journal of the International Anesthesia Research Society (IARS).

Rosiglitazone works by blocking a specific pathway—PPAR-gamma—which appears to play a critical role in the development of disabling neuropathic pain. "We therefore propose PPAR-gamma regulation of the macrophage-mediated inflammatory response as a novel therapeutic target for treating neuropathic pain development," concludes the study by Dr Yoshika Takahashi and colleagues of Juntendo University School of Medicine, Tokyo.

The researchers performed a series of experiments to evaluate rosiglitazone's effects on the development of abnormal pain responses and neuropathic pain. Neuropathic pain is a common and difficult-to-treat type of pain caused by nerve damage, seen in patients with trauma, diabetes, and other conditions. Phantom limb pain after amputation is an example of neuropathic pain.

The experiments used a standard technique to induce nerve injury in the hind leg of mice. They then evaluated the effects of rosiglitazone, administered in different ways, on the development of abnormal pain responses and neuropathic pain.

Treatment with rosiglitazone after nerve injury reduced the development of "tactile allodynia"—painful responses to stimuli (such as light touching) that are not normally painful. Rosiglitazone also led to decreased inflammation in the area of nerve injury, as shown by reduced levels of various inflammatory markers. The reduction in inflammation was associated with decreased responses by macrophages—immune cells that play a key role in the inflammatory response to injury.

The reductions in abnormal pain responses were seen with different forms of rosiglitazone administration—not only systemic injection, but also local injection directly into the site of nerve injury. Animals injected with rosiglitazone-treated macrophages also had reduced inflammation and pain responses.

Rosiglitazone was developed as an insulin-sensitizer for the treatment of diabetes. However, use of this medication has been restricted since it was linked to an increased risk of heart attack and other safety problems.

Since rosiglitazone blocks PPAR-gamma, the results strongly suggest that the PPAR-gamma pathway plays a critical role in the development of nerve inflammation and abnormal pain responses—and thus in the development of neuropathic pain. "Our results indicate that the activation of PPAR-gamma signaling in macrophages during the early phase may suppress neuropathic pain development," Dr Takahashi and co-authors write.

The study provides important new clues about the early stages of the "neuroinflammatory" response to nerve injury, leading to the development of allodynia and neuropathic pain. With further research, rosiglitazone or other drugs affecting PPAR-gamma and the macrophage-mediated pain response could provide a valuable new approach for prevention or treatment of neuropathic pain.

Source: News Release
International Anesthesia Research Society (IARS)
July 25, 2011

http://www.medmerits.com/index.php/article/diabetes_drug_may_help_prevent_neuropathic_pain