Hydrogen sulfide (H2S), produced via cystathionine-γ-lyase (CSE) is an endogenous gasotransmitter involved in signaling pathways that impact various aspects of physiological and pathological processes. It has been reported that increased levels of CSE and H2S accompany various disease states, including disorders characterized by inflammation and inflammatory pain, neuropathic disorders and neurodegenerative disorders, among others.

In relation to pain sensation and signaling, a significant effect of an increase in H2S concentration is known to occur via potentiation or direct activation of a variety of ion channels involved in nociception (TRPs) and neurotransmission (CaV, NaV). For example, it has been demonstrated in various reports that H2S can act, via sulfhydration, as an activator (TRPA1 and CaV3.2) or sensitizer (TRPV1) of these channels.

In addition, there is good experimental precedent in the literature demonstrating that blocking CSE activity with propargylglycine (PAG), an experimental compound know to be a non-specific inhibitor of CSE activity, produces anti-nociceptive responses in animals by altering H2S modulation of both TRP and Cav channels.