A Comprehensive Review on the Regulatory Action of TRP Channels: A Potential Therapeutic Target for Nociceptive Pain

Abstract

The transient receptor potential (TRP) superfamily of ion channels in humans comprises voltage-gated, non-selective cation channels expressed both in excitable as well as non-excitable cells. Four TRP channel subunits associate to create functional homo- or heterotetramers that allow the influx of calcium, sodium, and/or potassium. These channels are highly abundant in the brain and kidney and are important mediators of diverse biological functions including thermosensation, vascular tone, flow sensing in the kidney and irritant stimuli sensing. Inherited or acquired dysfunction of TRP channels influences cellular functions and signaling pathways resulting in multifaceted disorders affecting skeletal, renal, cardiovascular, and nervous systems. Studies have demonstrated the involvement of these channels in the generation and transduction of pain. Based on the multifaceted role orchestrated by these TRP channels, modulation of the activity of these channels presents an important strategy to influence cellular function by regulating intracellular calcium levels as well as membrane excitability. Therefore, there has been a remarkable pharmaceutical inclination toward TRP channels as therapeutic interventions. Several candidate drugs influencing the activity of these channels are already in the clinical trials pipeline. The present review encompasses the current understanding of TRP channels and TRP modulators in pain and pain management.

Osteosarcoma-Induced Pain Is Mediated by Glial Cell Activation in the Spinal Dorsal Horn, but Not Capsaicin-Sensitive Nociceptive Neurons: A Complex Functional and Morphological Characterization in Mice

“…This leads to the peripheral sensitization of the primary nociceptive neurons, resulting in hyperalgesia and allodynia. TRP vanilloid 1 (TRPV1) and ankyrin 1 (TRPA1) abundantly expressed on capsaicin-sensitive peptidergic sensory fibers have been suggested to be involved in chronic tumoral pain, including bone cancer [12]. The periosteum is densely innervated by these peptidergic nociceptive fibers being activated and sensitized by a broad range of mediators, such as bradykinin, endothelin, epidermal growth factor, glial cell line-derived neurotrophic factor, histamine, nerve growth factor, prostaglandins, tumor necrosis factor and vascular endothelial growth factor produced by tumor and immune cells [13,14].…”