PHARMACOLOGICAL AGENTS TARGETING TRANSIENT RECEPTOR POTENTIAL (TRP) CHANNELS IN NEUROPATHIC PAIN: PRECLINICAL AND CLINICAL STATUS

Abstract

Neuropathic pain generally affects 7-10% population worldwide and an estimated ∼1 in every 20 individuals in Western countries suffer and burden to society. The most limiting factor with existing therapies includes dose escalation issues, off-target side effects and poor translation of randomized trials into clinical practice. Neuropathic pain is a broad term that comprises direct injury/damage to the central and/or peripheral nervous system, leads to maladaptive changes in neuronal as well as in non-neuronal cells, which further contributes to the spontaneous pain, sensory and motor deficit along with altered sensitivity towards the noxious as well as non-noxious stimulus. Transient receptor potential (TRP) channels are polymodal, non-specific cation channels that operate as biosensors to various mechanical and chemical stimuli, including hyperosmolarity, shear stress, heat, mechanical stretch, extracellular ATP, and other products of inflammation. Modulation of these channels leads to various physiological and pathophysiological manifestations at molecular and cellular levels, leading to diseases including neuropathic pain. There are several molecules targeting TRP channels for neuropathic pain in pre-clinical studies, clinical trials and in the market. This review highlights the critical involvement of various pharmacological modulators for TRP channels targeting neuropathic pain and their possible outcomes to harness the therapeutic potential of TRP channels.