Peripheral voltage-gated calcium channels in skin are essential for transient neurogenic thermal hyperalgesia in mice
DuBreuil, D. M.; Lopez Soto, E. J.; Li, D.; Lipscombe, D.
Show abstract
Voltage-gated CaV2.2 calcium channels are expressed in nociceptors, at pre-synaptic terminals, soma, and axons. CaV2.2 channel inhibitors applied to the spinal cord relieve pain in humans and rodents, especially during pathological pain, but a biological function of nociceptor CaV2.2 channels in processing of nociception, outside pre-synaptic terminals, is not explored. Here, we demonstrate that functional CaV2.2 channels in skin are required for thermal hyperalgesia following intraplantar capsaicin exposure. We provide evidence that CaV2.2 channels at nociceptor free endings release inflammatory signals, ATP and IL-1{beta}. We assess the role of CaV2.2 splice isoforms to capsaicin-induced hyperalgesia measured by thermal and mechanical stimuli. Our data reveal a critical role for peripheral CaV2.2 channels in skin in neurogenic thermal hyperalgesia but not in mechanical hypersensitivity. Inhibition, or the complete lack, of peripheral CaV2.2 channels blunts the hyperalgesia response in vivo.
Matching journals
The top 3 journals account for 50% of the predicted probability mass.
Similar papers in this journal
- Enhanced Sodium Channel Inactivation by Temperature and FHF2 Deficiency Blocks Heat Nociception 97%
- Cortical astrocyte activation triggers meningeal nociception and migraine-like pain 96%
- The role of amygdala calcitonin gene-related peptide receptors on the development of persistent bladder pain in mice. 96%
Similar papers in this journal
- A role for protease activated receptor type 3 (PAR3) in nociception demonstrated through development of a novel peptide agonist 97%
- De novo expression of neuropeptide Y in sensory neurons does not contribute to peripheral neuropathic pain 97%
- The delta-opioid receptor bidirectionally modulates itch 96%
Similar papers in this journal
- Parabrachial nucleus activity in nociception and pain in awake mice 96%
- Endogenous inflammatory mediators produced by injury activate TRPV1 and TRPA1 nociceptors to induce sexually dimorphic cold pain that is dependent on TRPM8 and GFRalpha3 95%
- The neurokinin-1 receptor is expressed with gastrin-releasing peptide receptor in spinal interneurons and modulates itch 95%
Similar papers in this journal
- Neuropeptide Y-expressing dorsal horn inhibitory interneurons gate spinal pain and itch signalling 96%
- Human birth tissue products as a non-opioid medicine to inhibit post-surgical pain 96%
- A 'double-edged' role for type-5 metabotropic glutamate receptors in pain disclosed by light-sensitive drugs 95%
Similar papers in this journal
"Similar papers" are the closest papers from that journal in the model's embedding space. They show what the match is built on, but the ranking comes mostly from a classifier over the whole training set, not from these examples alone.