Voltage-gated calcium channels (VGCCs) permit depolarisation-dependent Ca2+ entry into excitable cells to control many functions, including neurotransmitter release in neurons, and muscle contraction. There are three distinct sub-families of VGCCs, CaV1 – 3. For the CaV1 and CaV2 sub-families, the channels are known to be heteromeric, consisting of an α1 pore-forming subunit, associated with auxiliary subunits β and α2δ. These auxiliary subunits modulate the functional expression and properties of the channels. In my lecture I will describe our studies on neuronal voltage-gated calcium channel tafficking, and relate this to studies of neuropathic pain mechanisms. In particular I will concentrate on the importance of the auxiliary α2δ subunits in CaV2.2 (N-type) calcium channel trafficking and function (Cassidy et al., 2014), and the key function of the Von Willebrand factor domain in α2δ-1 in this process (Canti et al., 2005; Hoppa et al., 2012; Cassidy et al., 2014). I will then describe how the α2δ ligands gabapentin and pregabalin, which are of therapeutic use in various neuropathic pain conditions, influence the trafficking of voltage-gated calcium channels. Related to this, I will describe evidence for the role of α2δ-1 in the development of neuropathic mechanical hypersensitivity in rodent models of neuropathic pain. The mRNA for α2δ-1 is among those that are strongly up-regulated in injured dorsal root ganglion (DRG) neurons, leading to an increase in α2δ-1 protein in DRG cell bodies, their axons and their terminals; such injuries lead to a chronic neuropathic pain-state (Bauer et al., 2009). Finally I will describe experiments in which we have characterised α2δ-1 knockout mice, and demonstrated that they show a marked delay in the onset of neuropathic hypersensitivity following nerve injury, indicating that α2δ-1 is essential to the rapid development of this condition (Patel et al., 2013).