| First Author | Lynch N | Year | 2025 |
| Journal | Adv Sci (Weinh) | Volume | 12 |
| Issue | 35 | Pages | e00325 |
| PubMed ID | 40583282 | Mgi Jnum | J:387272 |
| Mgi Id | MGI:8347873 | Doi | 10.1002/advs.202500325 |
| Citation | Lynch N, et al. (2025) Calcitonin Gene-Related Peptide (CGRP)-Expressing Neurons in the External Lateral Parabrachial Area Regulate Pain-Induced Sleep Disturbances. Adv Sci (Weinh) 12(35):e00325 |
| abstractText | Given that sleep and pain are bidirectionally related, we investigated the neural circuits underlying pain-induced sleep disturbances using two acute pain models. Activation of nociceptors in acute inflammatory pain (AIP) significantly reduced sleep by 45-50% in the first 6 h, with reduced sleep spindle density for 1-3 h post-AIP. Additionally, an "optogenetic pain (Opto-Pain)" model is implemented to produce acute peripheral pain-induced awakenings that reduced sleep comparable to AIP. Both pain models are used to test the role of wake-promoting neurons in the parabrachial nucleus that express Calcitonin Gene-Related Peptide (PBel(CGRP)) in relaying nociceptive stimulus from the dorsal horn as part of the spine-ponto-amygdaloid tract. Blocking PBel(CGRP) neurons with genetic ablation or optogenetic inhibition attenuated sleep loss. To dissect the PBel(CGRP) pathways, the terminals are then optogenetically silenced post-AIP and found the reversal of sleep disturbances in the following descending order of effectiveness: substantia innominata of the basal forebrain (SI-BF) > central nucleus of the amygdala (CeA) > bed nucleus of the stria terminalis (BNST) > the lateral hypothalamus (LH). In SI-BF and CeA, a similar reversal of AIP-induced sleep loss occurred with pharmacological blocking of either CGRP or NMDA receptors. The results are relevant to emerging pain therapies aiming to attenuate sleep disturbances. |
