In Vivo application of RNAi to study pain

Abstract

Chronic pain is associated with several disease conditions. The inadequacy of current analgesics to treat chronic pain is the result of a lack of understanding of the mechanisms that mediate pain. RNA interference has emerged in recent years as a new way to evaluate the roles of molecules involved in the pain response. Selective knockout of proteins has proven to be a powerful technique for target validation, but has been limited as a potential therapeutic due to short-lived responses induced by RNAi. The short responses of RNAi illustrate the need for better delivery techniques, which is being addressed by current work to induce RNAi through the cell’s natural mechanisms. In order to gain a better understanding of chronic pain, it will be necessary to evaluate the pain molecules that are expressed as part of an injury induced pain response, which can be modeled by contusion spinal cord injury. RNAi will prove to be an important technique in this work. The present minireview will summarize the work that has been done using RNAi in vivo to study pain and discuss future directions for the use of RNAi to study chronic pain.

Practical Considerations of Convection Enhanced Delivery for Novel Therapies Treating Spinal Cord Injury Related Neuropathic Pain

“…There are current limitations in the use of RNAi short response as a delivery technique to stimulate RNAi through the cell's natural mechanisms. A mini review from our lab documented the work done on pain using RNAi in vivo [4].…”

Gene Delivery Strategies to Promote Spinal Cord Repair

“…RNA interference (RNAi), which includes small interfering RNA (siRNA) and microRNA (miRNA), is commonly used to reduce or knock out expression of specific genes. 24 Effects of various RNAi have been investigated extensively in the context of spinal cord repair 25–29 and is an important tool for studying SCI. While siRNA is usually highly specific for a particular gene and completely knocks out its expression, miRNA is more promiscuous and can regulate hundreds of mRNA sequences, resulting in various levels of inhibition.…”

RNA interference-based functional knockdown of the voltage-gated potassium channel Kv7.2 in dorsal root ganglion neurons after in vitro and in vivo gene transfer by adeno-associated virus vectors

“…In our present study, we resolved this dilemma by using RNA interference (RNAi), which is an alternative approach for target validation and in addition provides new treatment options. 10 , 11 We and others have shown that RNAi-mediated silencing has potential to study pain biology. 12 – 16 In fact, a small interfering RNA (siRNA) targeting the Transient Receptor Potential Vanilloid 1 receptor has already reached the status of clinical testing for the treatment of ocular pain.…”