Voltage-gated calcium channels (VGCCs) play important roles in physiological functions including the modulation of neurotransmitter release, neuronal network activities, intracellular signalling pathways and gene expression. Some pathological conditions, including nerve injuries, can cause the dysregulation of VGCCs and their subunits. This in turn can lead to a functional maladaptation of VGCCs and their subunits, which can contribute to the development of disorders such as pain sensations. This review has summarized recent findings related to maladaptive changes in the dysregulated VGCC α2 δ1 subunit (Cav α2 δ1 ) with a focus on exploring the mechanisms underlying the contribution of Cav α2 δ1 to pain signal transduction. At least under neuropathic pain conditions, the dysregulated Cav α2 δ1 can modulate VGCC functions as well as other plasticity changes. The latter includes abnormal excitatory synaptogenesis resulting from its interactions with injury-induced extracellular matrix glycoprotein molecule thrombospondins, which is independent of the VGCC functions. Blocking Cav α2 δ1 with gabapentinoids can reverse neuropathic pain significantly with relatively mild side effects, but only in a small population of neuropathic pain patients due to reasons yet to be explored. There are emerging data suggesting that early preventive treatment with gabapentinoids can prevent aberrant excitatory synapse formation and the development of chronic pain. If these findings are confirmed clinically, this could be an attractive approach for neuropathic pain management.

Currently, the multifaceted role of the extracellular matrix (ECM) in tumourigenesis has been realized. One ECM macromolecule exhibiting potent oncosuppressive actions in tumourigenesis is decorin, the prototype of the small leucine-rich proteoglycan gene family. The actions of decorin include its ability to function as an endogenous pan-receptor tyrosine kinase inhibitor, a regulator of both autophagy and mitophagy, as well as a modulator of the immune system. In this review, we will discuss these topics in more detail. We also provide a summary of preclinical studies exploring the value of decorin-mediated oncosuppression, as a potential future adjuvant therapy for epithelial cancers. LINKED ARTICLES: This article is part of a themed section on Translating the Matrix. To view the other articles in this section visit http://onlinelibrary.wiley.com/doi/10.1111/bph.v176.1/issuetoc.