Nociceptor spontaneous activity is responsible for fragmenting non-rapid eye movement sleep in mouse models of neuropathic pain.

Autor: Alexandre C; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Miracca G; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.; FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Holanda VD; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Sharma A; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Kourbanova K; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Ferreira A; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA.; FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Bicca MA; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Zeng X; FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Nassar VA; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA., Lee S; FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Kaur S; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA., Sarma SV; Department of Biomedical Engineering, Johns Hopkins University, Baltimore, MD 21205, USA., Sacré P; Department of Electrical Engineering and Computer Science, School of Engineering, University of Liège, Liège, Belgium., Scammell TE; Department of Neurology, Beth Israel Deaconess Medical Center, Harvard Medical School, Boston, MA 02115, USA., Woolf CJ; FM Kirby Neurobiology Center, Boston Children's Hospital and Department of Neurobiology, Harvard Medical School, Boston, MA 02115, USA., Latremoliere A; Department of Neurosurgery, Neurosurgery Pain Research Institute, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.; Department of Neuroscience, Johns Hopkins School of Medicine, Baltimore, MD 21205, USA.
Jazyk: angličtina
Zdroj: Science translational medicine [Sci Transl Med] 2024 Apr 17; Vol. 16 (743), pp. eadg3036. Date of Electronic Publication: 2024 Apr 17.
DOI: 10.1126/scitranslmed.adg3036
Abstrakt: Spontaneous pain, a major complaint of patients with neuropathic pain, has eluded study because there is no reliable marker in either preclinical models or clinical studies. Here, we performed a comprehensive electroencephalogram/electromyogram analysis of sleep in several mouse models of chronic pain: neuropathic (spared nerve injury and chronic constriction injury), inflammatory (Freund's complete adjuvant and carrageenan, plantar incision) and chemical pain (capsaicin). We find that peripheral axonal injury drives fragmentation of sleep by increasing brief arousals from non-rapid eye movement sleep (NREMS) without changing total sleep amount. In contrast to neuropathic pain, inflammatory or chemical pain did not increase brief arousals. NREMS fragmentation was reduced by the analgesics gabapentin and carbamazepine, and it resolved when pain sensitivity returned to normal in a transient neuropathic pain model (sciatic nerve crush). Genetic silencing of peripheral sensory neurons or ablation of CGRP + neurons in the parabrachial nucleus prevented sleep fragmentation, whereas pharmacological blockade of skin sensory fibers was ineffective, indicating that the neural activity driving the arousals originates ectopically in primary nociceptor neurons and is relayed through the lateral parabrachial nucleus. These findings identify NREMS fragmentation by brief arousals as an effective proxy to measure spontaneous neuropathic pain in mice.
Databáze: MEDLINE