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