Opioids act through G-inhibitory protein-coupled opioid receptors located on central and peripheral pain-sensing neurons. Mechanisms involved in opioid analgesia include activation of G-protein-gated inwardly rectifying K+ (GIRK) channels and inhibition of voltage-gated Ca2+ channels. We examine GIRK/opioid receptor coupling in peripheral sensory neurons and its impact on peripheral opioid analgesia in inflammatory pain (Nockemann et al., EMBO Mol Med 2013; Stötzner et al. Front Pharmacol 2018). We also investigate other ion channels such as transient receptor potential A (TRPA) and the interactions between opioid receptors and vanilloid receptor type 1 (TRPV1) during withdrawal of chronically applied opioid as well as in the peripheral inhibition of neuropathic pain. We utilize in vivo analgesia testing, ex vivo electrophysiological patch clamp recordings, Ca2+- and K+-imaging in naïve and pathological pain conditions (Spahn et al., Pain 2013; Spahn et al., Mol Pharmacol 2014; Spahn et al., Methods Mol Biol 2015; Labuz et al., Neuropharmacology 2016).
Group members involved: Christoph Stein, Halina Machelska, Dinah Nockemann, Viola Seitz, Philip Stötzner, Sandeep Dembla