α2δ-1 Gene Deletion Affects Somatosensory Neuron Function and Delays Mechanical Hypersensitivity in Response to Peripheral Nerve Damage

• DOI: 10.1523/jneurosci.1026-13.2013
• Publication Date: 2013-10-16T19:07:34Z
• Authors: Ryan Patel; Claudia S. Bauer; Manuela Nieto-Rostro; Wojciech Margas; Laurent Ferron; Kanchan Chaggar; Kasumi Crews; Juan D. Ramirez; David L. H. Bennett; Arnold Schwartz; Anthony H. Dickenson; Annette C. Dolphin
• Keywords: Nerve Injury

The α2δ-1 subunit of voltage-gated calcium channels is upregulated after sensory nerve injury and also the therapeutic target gabapentinoid drugs. It therefore likely to play a key role in development neuropathic pain. In this study, we have examined mice which gene expression disrupted, determine whether involved various modalities nociception, for behavioral hypersensitivity partial sciatic ligation (PSNL). We find that naive α2δ-1(-/-) show marked deficit mechanical cold sensitivity, but no change thermal nociception threshold. lower sensitivity mirrored by reduced vivo electrophysiological response dorsal horn wide dynamic range neurons. CaV2.2 level brain spinal cord synaptosomes from mice, DRG neurons exhibit channel current density. Furthermore, significantly smaller number respond TRPM8 agonist menthol. After PSNL, delayed hypersensitivity, only develops at 11 d surgery, whereas wild-type littermates it maximal earliest time point measured (3 d). There compensatory upregulation α2δ-2 or α2δ-3 PSNL other transcripts, including neuropeptide Y activating transcription factor-3, are normally. ability pregabalin alleviate lost mice. Thus, essential rapid model