cGMP signalling in dorsal root ganglia and the spinal cord: Various functions in development and adulthood

Abstract

Cyclic GMP (cGMP) is a second messenger that regulates numerous physiological and pathophysiological processes. In recent years, more and more studies have uncovered multiple roles of cGMP signalling pathways in the somatosensory system. Accumulating evidence suggests that cGMP regulates different cellular processes from embryonic development through adulthood. During embryonic development, a cGMP-dependent signalling cascade in the trunk sensory system is essential for axon bifurcation, a specific form of branching of somatosensory axons. In adulthood, various cGMP signalling pathways in distinct cell populations of sensory neurons and dorsal horn neurons in the spinal cord play an important role in the processing of pain and itch. Some of the involved enzymes might serve as a target for future therapies. In this review, we summarize the knowledge regarding cGMP-dependent signalling pathways in dorsal root ganglia and the spinal cord during embryonic development and adulthood, and the future potential of targeting these pathways.

Association between single nucleotide variants and severe chronic pain in older adult patients after lower extremity arthroplasty

“…Other studies have shown that the serum level of soluble intercellular adhesion molecule-1 (sICAM-1) is significantly correlated with the pain intensity of patients, suggesting that sICAM-1 can be used as a biomarker of pain intensity [33]. The cGMP signaling pathway plays an important role in the processing of pain by sensory neurons and dorsal horn neurons [42]. Phosphatidylinositol bisphosphate (PIP2) is located at the key convergence point of multiple receptors, ion channels, and signal pathways that promote chronic pain.…”

Epitope-tagged and phosphomimetic mouse models for investigating natriuretic peptide-stimulated receptor guanylyl cyclases

“…Only a small subset of tissues was examined here, and previous studies indicate that many other tissues (including nerves, vasculature, and adipocytes) express these proteins as well ( Kuhn, 2016 ; Schmidt et al, 2018 , 2022 ). Because antibodies that are highly specific for NPR1 and NPR2 are not commercially available, mice expressing HA-tagged NPR1 and NPR2 will be useful for future studies evaluating protein expression levels in other tissues.…”

“…Atrial natriuretic peptide (ANP) and brain natriuretic peptide (BNP) activate NPR1 to reduce blood pressure and cardiac hypertrophy and to regulate metabolism ( Kuhn, 2016 ; Wagner et al, 2022a ). C-type natriuretic peptide (CNP) activates NPR2 to regulate bone growth and oocyte meiosis ( Kuhn, 2016 ; Jaffe and Egbert, 2017 ; see sections “Results and discussion”), as well as axon bifurcation ( Schmidt et al, 2018 , 2022 ) and cardiovascular remodeling and contractility ( Kuhn, 2016 ; Subramanian et al, 2018 ).…”

The 10th International Conference on cGMP 2022: recent trends in cGMP research and development—meeting report

“…Recent live cell fluorescence imaging of primary hippocampal neurons isolated from mice lacking NO-GC1 or NO-GC2, which were crossed with cGi-500-expressing cGMP indicator mice, revealed that NO-GC2 plays the predominant role in the generation of cGMP signals induced by N -methyl-d-aspartate (NMDA) and AMPA (α-amino-3-hydroxy-5-methyl-4-isoxazole propionic acid) glutamate receptors (Doris Koesling, Bochum). Furthermore, the observation that NMDA- and AMPA-induced cGMP signals are modulated by PDE inhibitors in a specific manner points to different pools of cGMP in the hippocampus, most likely in specific compartments equipped with distinct sets of PDEs (Giesen et al 2022 ).cGMP also has essential functions in mammalian embryonic development (Schmidt et al 2022 ). One important cGMP-dependent process is neuronal polarization, in which neurons form the distinct compartments of the dendrite and the axon.…”