Background & Aims

Painful Diabetic Peripheral Neuropathy (PDPN) is one of the major complications of diabetes. Currently, centrally acting drugs and topical analgesics are used for treating PDPN. These drugs have adverse effects, some are ineffective and treatment with opioids is associated with use dependence and addiction. Recent research indicates that Transient Receptor Potential Vanilloid 1 (TRPV1) expressed in the peripheral sensory nerve terminals is an emerging target to treat pain associated with PDPN.

Methods

Application of RTX cream to the hind limbs suppresses thermal hyperalgesia in streptozotocin (STZ)-induced diabetic rats and mini-pigs without any adverse effects as compared to capsaicin at therapeutic doses, which induces intense pain during application.

Results

RTX cream also decreases the expression of TRPV1 in the peripheral nerve endings and suppresses TRPV1-mediated CGRP release in the skin samples of diabetic rats and mini-pigs. Our preclinical data confirm that RTX topical formulation is an effective treatment option for PDPN.

Conclusions

RTX is an ultrapotent TRPV1 agonist
Very low concentrations of RTX induces depolarization block and prevents transmission of painful signals from peripheral nerve
terminals
Nanoparticle RTX cream formulation penetrates well into skin layers
RTX cream reduces thermal and mechanical hypersensitivity in diabetic rats
RTX cream reduces thermal hypersensitivity in mini-pig model of diabetes
Our preclinical data confirm that RTX topical formulation is an effective treatment option for painful diabetic peripheral neuropathy

References

1. Jeffry JA et al.,. PLoS One 2009;4(9):e7021; 2. Pabbidi RM et al. Mol Pain 2008;4:9; 3. Mitchell K et al., Mol Pain 2010;6:94; 4. Moeller-Bertram T et al., Pain Med 2013;14(3):417-421; 5; Tzabazis AZ et al.,
Mol Pain 2011;7:18. 6. Yan Z. https://faculty.virginia.edu/yanlab/Protocols/Western blot quantification by Image J.pdf. 2019.

Presenting Author

Louis Premkumar

Poster Authors

Louis Premkumar

Ph.D

Southern Illinois University School of Medicine

Lead Author

E-mail

Topics

  • Specific Pain Conditions/Pain in Specific Populations: Neuropathic Pain - Peripheral

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