Search citation statements
Paper Sections
Citation Types
Year Published
Publication Types
Relationship
Authors
Journals
Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours. This relationship is facilitated by the transmission of nociceptive signals through the spino-parabrachial pathways, converging at the wake-active PBelCGRP(parabrachial nucleus expressing Calcitonin Gene-Related Peptide) neurons, known to gate aversive stimuli. However, it has never been tested whether the targeted blocking of this wake pathway can alleviate pain-induced sleep disturbances without increasing sleepiness. Therefore, we next used selective ablations or optogenetic silencing and identified the key role played by the glutamatergic PBelCGRPin pain-induced sleep disturbances. Inactivating the PBelCGRPneurons by genetic deletion or optogenetic silencing prevented these sleep disturbances in both pain models. Furthermore, to understand the wake pathways underlying the pain-induced sleep disturbances, we silenced the PBelCGRPterminals at four key sites in the substantia innominata of the basal forebrain (SI-BF), the central nucleus of Amygdala (CeA), the bed nucleus of stria terminalis (BNST), or the lateral hypothalamus (LH). Silencing of the SI-BF and CeA also significantly reversed pain-induced sleep loss, specifically through the action on the CGRP and NMDA receptors. This was also confirmed by site-specific blockade of these receptors pharmacologically. Our results highlight the significant potential for selectively targeting the wake pathway to effectively treat pain and sleep disturbances, which will minimize risks associated with traditional analgesics.One sentence summaryParabrachial CGRP neurons regulate awakenings to pain.
Pain therapies that alleviate both pain and sleep disturbances may be the most effective for pain relief, as both chronic pain and sleep loss render the opioidergic system, targeted by opioids, less sensitive and effective for analgesia. Therefore, we first studied the link between sleep disturbances and the activation of nociceptors in two acute pain models. Activation of nociceptors in both acute inflammatory (AIP) and opto-pain models led to sleep loss, decreased sleep spindle density, and increased sleep fragmentation that lasted 3 to 6 hours. This relationship is facilitated by the transmission of nociceptive signals through the spino-parabrachial pathways, converging at the wake-active PBelCGRP(parabrachial nucleus expressing Calcitonin Gene-Related Peptide) neurons, known to gate aversive stimuli. However, it has never been tested whether the targeted blocking of this wake pathway can alleviate pain-induced sleep disturbances without increasing sleepiness. Therefore, we next used selective ablations or optogenetic silencing and identified the key role played by the glutamatergic PBelCGRPin pain-induced sleep disturbances. Inactivating the PBelCGRPneurons by genetic deletion or optogenetic silencing prevented these sleep disturbances in both pain models. Furthermore, to understand the wake pathways underlying the pain-induced sleep disturbances, we silenced the PBelCGRPterminals at four key sites in the substantia innominata of the basal forebrain (SI-BF), the central nucleus of Amygdala (CeA), the bed nucleus of stria terminalis (BNST), or the lateral hypothalamus (LH). Silencing of the SI-BF and CeA also significantly reversed pain-induced sleep loss, specifically through the action on the CGRP and NMDA receptors. This was also confirmed by site-specific blockade of these receptors pharmacologically. Our results highlight the significant potential for selectively targeting the wake pathway to effectively treat pain and sleep disturbances, which will minimize risks associated with traditional analgesics.One sentence summaryParabrachial CGRP neurons regulate awakenings to pain.
BackgroundMontrichardia linifera (Arruda) Schott is popularly known as “aninga,” “aningaçu,” “aningaíba,” and “aninga-do-igapó.” Compresses and plasters made from the leaves of this medicinal plant are used to treat abscesses, tumors, and pain caused by stingray stings.Aim of the studyThis study aimed to chemically characterize the methanolic extract of M. linifera leaves (MEMLL), as well as to verify their acute oral toxicity and antinociceptive potential.Materials and methodsThe leaves were collected during the rainy season, and the methanolic extract was obtained after gradient extraction using different solvents. MEMLL was analyzed using high-performance liquid chromatography (HPLC) and nuclear magnetic resonance (NMR). Acute oral toxicity testing followed the Organization for Economic Co-operation and Development (OECD) guideline 423. Subsequently, acetic acid, hot plate, and formalin tests were used to evaluate the analgesic effects.ResultsIn the chemical characterization of MEMLL by HPLC, three flavonoids were identified: rutin, quercetin, and epicatechin. In addition, when NMR spectroscopy was performed, rutin and quercetin were again identified, as well as the chemical compounds luteolin and chrysoeriol. In the acute oral toxicity test, MEMLL showed no physiological or behavioral changes. In the nociceptive study, MEMLL showed an effect at doses of 50 and 100 mg/kg in the 0.6% acetic acid test, i.e., 51.46% and 75.08%, respectively. In the hot plate test, the MEMLL group at a dose of 50 mg/kg was effective at times of 30 and 60 min, i.e., 164.43% and 122.95%, respectively. Similarly, the MEMLL group at a dose of 100 mg/kg was also effective in increasing latency at times of 30 and 60 min, i.e., 162.62% and 136.68%, respectively. In the formalin test, MEMLL showed an antinociceptive effect on neurogenic pain at doses of 50 and 100 mg/kg when compared to the control group, 35.25% and 52.30%, respectively. In the inflammatory phase, inhibition was observed in the MEMLL at doses of 50 and 100 mg/kg, i.e., 66.39% and 72.15%, respectively.ConclusionMEMLL has analgesic properties and is non-toxic, validating the Brazilian ethnopharmacological use of this plant for pain treatment. The leaves of the species M. linifera showed central and peripheral antinociceptive effects.
scite is a Brooklyn-based organization that helps researchers better discover and understand research articles through Smart Citations–citations that display the context of the citation and describe whether the article provides supporting or contrasting evidence. scite is used by students and researchers from around the world and is funded in part by the National Science Foundation and the National Institute on Drug Abuse of the National Institutes of Health.
customersupport@researchsolutions.com
10624 S. Eastern Ave., Ste. A-614
Henderson, NV 89052, USA
This site is protected by reCAPTCHA and the Google Privacy Policy and Terms of Service apply.
Copyright © 2025 scite LLC. All rights reserved.
Made with 💙 for researchers
Part of the Research Solutions Family.