Olfactory stimulation Inhibits Nociceptive Signal Processing at the Input Stage of the Central Trigeminal System

Papotto, Nunzia; Reithofer, Sara; Baumert, Kaya; Carr, Richard W.; Möhrlen, Frank; Frings, Stephan

doi:10.1016/j.neuroscience.2021.10.018

Cited by 8 publications

(4 citation statements)

References 73 publications

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“…In adults with chronic back pain, scent training did not change pain intensity but led to an increased pain threshold ( 17 ), which is in line with the results of the current study in children with recurrent headaches. Data in mice showed reduced activation of the spinal trigeminal nucleus caudalis after olfactory costimulation with floral odorants and the application of a trigeminal pain stimulus ( 34 ). However, this study refers to changes in the caudal nucleus of the trigeminal nerve after scent exposure.…”

Section: Discussionmentioning

confidence: 99%

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches

Goßrau

Zaranek²,

Klimová³

et al. 2023

Front. Pain Res.

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ObjectiveHeadache prevalence among children and adolescents has increased over the last few years. Evidence-based treatment options for pediatric headaches remain limited. Research suggests a positive influence of odors on pain and mood. We investigated the effect of repeated exposure to odors on pain perception, headache-related disability, and olfactory function in children and adolescents with primary headaches.MethodsEighty patients with migraine or tension-type headache (mean 13.1 ± 3.29 years) participated, of whom 40 underwent daily olfactory training with individually selected pleasant odors for 3 months and 40 received state-of-the-art outpatient therapy as a control group. At baseline and after a 3-month follow-up, olfactory function [odor threshold; odor discrimination; odor identification; comprehensive Threshold, Discrimination, Identification (TDI) score], mechanical detection and pain threshold (quantitative sensory testing), electrical pain threshold, patient-reported outcomes on headache-related disability [Pediatric Migraine Disability Assessment (PedMIDAS)], pain disability [Pediatric Pain Disability Index (P-PDI)], and headache frequency were assessed.ResultsTraining with odors significantly increased the electrical pain threshold compared to the control group (U = 470.000; z = −3.177; p = 0.001). Additionally, olfactory training significantly increased the olfactory function (TDI score [t(39) = −2.851; p = 0.007], in particular, olfactory threshold, compared to controls (U = 530.500; z = −2.647; p = 0.008). Headache frequency, PedMIDAS, and P-PDI decreased significantly in both groups without a group difference.ConclusionsExposure to odors has a positive effect on olfactory function and pain threshold in children and adolescents with primary headaches. Increased electrical pain thresholds might reduce sensitization for pain in patients with frequent headaches. The additional favorable effect on headache disability without relevant side effects underlines the potential of olfactory training as valuable nonpharmacological therapy in pediatric headaches.

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Section: Discussionmentioning

confidence: 99%

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches

Goßrau

Zaranek²,

Klimová³

et al. 2023

Front. Pain Res.

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“…The SpVc, SSP and NAc have all been previously implicated in the pathophysiology of headache and in pain processing (74)(75)(76)(77). Meningeal nociceptive afferents enter the brainstem via the trigeminal tract and pass caudally while giving off collaterals that terminate in the SpVc (13,74,78).…”

Section: Discussionmentioning

confidence: 99%

Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache

Rudolph,

Kopruszinski,

et al. 2023

Cephalalgia

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Background Post-traumatic headache is very common after a mild traumatic brain injury. Post-traumatic headache may persist for months to years after an injury in a substantial proportion of people. The pathophysiology underlying post-traumatic headache remains unknown but is likely distinct from other headache disorders. Identification of brain areas activated in acute and persistent phases of post-traumatic headache can provide insights into the underlying circuits mediating headache pain. We used an animal model of mild traumatic brain injury-induced post-traumatic headache and c-fos immunohistochemistry to identify brain regions with peak activity levels across the acute and persistent phases of post-traumatic headache. Methods Male and female C57BL/6 J mice were briefly anesthetized and subjected to a sham procedure or a weight drop closed-head mild traumatic brain injury . Cutaneous allodynia was assessed in the periorbital and hindpaw regions using von Frey filaments. Immunohistochemical c-fos based neural activity mapping was then performed on sections from whole brain across the development of post-traumatic headache (i.e. peak of the acute phase at 2 days post- mild traumatic brain injury), start of the persistent phase (i.e. >14 days post-mild traumatic brain injury) or after provocation with stress (bright light). Brain areas with consistent and peak levels of c-fos expression across mild traumatic brain injury induced post-traumatic headache were identified and included for further analysis. Results Following mild traumatic brain injury, periorbital and hindpaw allodynia was observed in both male and female mice. This allodynia was transient and subsided within the first 14 days post-mild traumatic brain injury and is representative of acute post-traumatic headache. After this acute post-traumatic headache phase, exposure of mild traumatic brain injury mice to a bright light stress reinstated periorbital and hindpaw allodynia for several hours – indicative of the development of persistent post-traumatic headache. Acute post-traumatic headache was coincident with an increase in neuronal c-fos labeling in the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and the nucleus accumbens. Neuronal activation returned to baseline levels by the persistent post-traumatic headache phase in the spinal nucleus of the trigeminal caudalis and primary somatosensory cortex but remained elevated in the nucleus accumbens. In the persistent post-traumatic headache phase, coincident with allodynia observed following bright light stress, we observed bright light stress-induced c-fos neural activation in the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and nucleus accumbens. Conclusion Examination of mild traumatic brain injury-induced changes in peak c-fos expression revealed brain regions with significantly increased neural activity across the acute and persistent phases of post-traumatic headache. Our findings suggest mild traumatic brain injury-induced post-traumatic headache produces neural activation along pain relevant pathways at time-points matching post-traumatic headache-like pain behaviors. These observations suggest that the spinal nucleus of the trigeminal caudalis, primary somatosensory cortex, and nucleus accumbens may contribute to both the induction and maintenance of post-traumatic headache.

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“…Ptf1a -negative dBLb-derived neurons become excitatory and co-express Prrxl1 , Pou4fl, Tlx3 and Lmx1b [ 4 , 44 , 59 ]. The SPV receives nociceptive signaling from the head and somatosensory signaling [ 64 , 66 ]. Furthermore, dBLa-derived neurons become part of the NTS, next to the neurons of the dB1 domain, and specifically express Gad67 and Pax2 [ 26 ].…”

Section: Molecular Patterning Of the Medulla Oblongata And Neuronal D...mentioning

confidence: 99%

Molecular Organization and Patterning of the Medulla Oblongata in Health and Disease

Diek

Smidt

Mesman

2022

IJMS

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The medulla oblongata, located in the hindbrain between the pons and the spinal cord, is an important relay center for critical sensory, proprioceptive, and motoric information. It is an evolutionarily highly conserved brain region, both structural and functional, and consists of a multitude of nuclei all involved in different aspects of basic but vital functions. Understanding the functional anatomy and developmental program of this structure can help elucidate potential role(s) of the medulla in neurological disorders. Here, we have described the early molecular patterning of the medulla during murine development, from the fundamental units that structure the very early medullary region into 5 rhombomeres (r7–r11) and 13 different longitudinal progenitor domains, to the neuronal clusters derived from these progenitors that ultimately make-up the different medullary nuclei. By doing so, we developed a schematic overview that can be used to predict the cell-fate of a progenitor group, or pinpoint the progenitor domain of origin of medullary nuclei. This schematic overview can further be used to help in the explanation of medulla-related symptoms of neurodevelopmental disorders, e.g., congenital central hypoventilation syndrome, Wold–Hirschhorn syndrome, Rett syndrome, and Pitt–Hopkins syndrome. Based on the genetic defects seen in these syndromes, we can use our model to predict which medullary nuclei might be affected, which can be used to quickly direct the research into these diseases to the likely affected nuclei.

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Olfactory stimulation Inhibits Nociceptive Signal Processing at the Input Stage of the Central Trigeminal System

Cited by 8 publications

References 73 publications

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches

Olfactory training reduces pain sensitivity in children and adolescents with primary headaches

Identification of brain areas in mice with peak neural activity across the acute and persistent phases of post-traumatic headache

Molecular Organization and Patterning of the Medulla Oblongata in Health and Disease

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