TRPV1 and Diabetic Neuropathy

Thermal hyperalgesia is a common sympton of Diabetic Periperal Neuropathy (DPN). It is one of most difficult types of pain to treat. The development of tolerance, inadequate relief and potential toxicity of classical antinociceptives warrant the investigation of the newer agents to relieve this pain.

The elevated expression of Transient receptor potential vanilloid 1 (TRPV1) suspected as a transmitter of this pain. Dr. Louis Premkumar and his team at SIU have recently published results that further demonstrate the role of TRPV1: Mahendra Bishnoi, Christine A Bosgraaf, Mruvil Abooj, Linlin Zhong, Louis S Premkumar. Streptozotocin-Induced Early Thermal Hyperalgesia is independent of Glycemic State of Rats: Role of Transient Receptor Potential Vanilloid 1(TRPV1) and inflammatory mediators. Molecular Pain 2011, 7:52 doi:10.1186/1744-8069-7-52. Published: 27 July 2011.

Figure 4. Altered TRPV1 staining in spinal cord dorsal horn of STZ-treated rats. A. Representative images of TRPV1 staining from a vehicle-treated, STZ-HG and STZNG rats. An enlarged segment has also been shown. B. Average gray values/10,000 μm² area of TRPV1 staining in dorsal horn was significantly increased (p<0.05) in both STZ-HG and STZ-NG rats as compared to vehicle-treated rats. Asterisk (*) represents p < 0.05. Scale bar is 200 μm and 50 μm for upper and lower panels, respectively.

Conclusions: From these results, it is concluded that TRPV1 is an integral component of initiating and maintaining inflammatory thermal hyperalgesia, which can be alleviated by intrathecal administration of RTX. Further, the results suggest that enhanced expression and inflammation-induced sensitization of TRPV1 at the spinal cord may play a role in central sensitization in STZ-induced neuropathy.

Therapies that downregulate or silence TRPV1 expression could be the key to better treatments for the Thermal Algesia cause by diabetes. I will keep you posted.