Pain is a complex multidimensional concept that facilitates the initiation of the signaling
cascade in response to any noxious stimuli. Action potential generation in the peripheral nociceptor
terminal and its transmission through various types of nociceptors corresponding to mechanical,
chemical or thermal stimuli lead to the activation of receptors and further neuronal processing produces
the sensation of pain. Numerous types of receptors are activated in pain sensation which vary in
their signaling pathway. These signaling pathways can be regarded as a site for modulation of pain by
targeting the pain transduction molecules to produce analgesia. On the basis of their anatomic location,
transient receptor potential ion channels (TRPV1, TRPV2 and TRPM8), Piezo 2, acid-sensing
ion channels (ASICs), purinergic (P2X and P2Y), bradykinin (B1 and B2), α-amino-3-hydroxy-5-
methylisoxazole-4-propionate (AMPA), N-methyl-D-aspartate (NMDA), metabotropic glutamate
(mGlu), neurokinin 1 (NK1) and calcitonin gene-related peptide (CGRP) receptors are activated during
pain sensitization. Various inhibitors of TRPV1, TRPV2, TRPM8, Piezo 2, ASICs, P2X, P2Y, B1,
B2, AMPA, NMDA, mGlu, NK1 and CGRP receptors have shown high therapeutic value in experimental
models of pain. Similarly, local inhibitory regulation by the activation of opioid, adrenergic,
serotonergic and cannabinoid receptors has shown analgesic properties by modulating the central and
peripheral perception of painful stimuli. This review mainly focused on various classes of nociceptors
involved in pain transduction, transmission and modulation, site of action of the nociceptors in modulating
pain transmission pathways and the drugs (both clinical and preclinical data, relevant to targets)
alleviating the painful stimuli by exploiting nociceptor-specific channels and receptors.
Activation of cannabinoid receptors by the pentacyclic triterpene α,β-amyrin inhibits inflammatory and neuropathic persistent pain in mice: erratum
