Brainstem pain-control circuitry connectivity in chronic neuropathic pain
© 2018 the authors. Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modul...
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| Format: | Journal Article |
| Language: | English |
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SOC NEUROSCIENCE
2018
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| Online Access: | http://purl.org/au-research/grants/nhmrc/1032072 http://hdl.handle.net/20.500.11937/79562 |
| _version_ | 1848764074666491904 |
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| author | Mills, E.P. Di Pietro, Flavia Alshelh, Z. Peck, C.C. Murray, G.M. Vickers, E.R. Henderson, L.A. |
| author_facet | Mills, E.P. Di Pietro, Flavia Alshelh, Z. Peck, C.C. Murray, G.M. Vickers, E.R. Henderson, L.A. |
| author_sort | Mills, E.P. |
| building | Curtin Institutional Repository |
| collection | Online Access |
| description | © 2018 the authors.
Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top–down engagement of the circuitry alongside altered reward processing in pain conditions. |
| first_indexed | 2025-11-14T11:13:35Z |
| format | Journal Article |
| id | curtin-20.500.11937-79562 |
| institution | Curtin University Malaysia |
| institution_category | Local University |
| language | English |
| last_indexed | 2025-11-14T11:13:35Z |
| publishDate | 2018 |
| publisher | SOC NEUROSCIENCE |
| recordtype | eprints |
| repository_type | Digital Repository |
| spelling | curtin-20.500.11937-795622021-01-08T07:54:27Z Brainstem pain-control circuitry connectivity in chronic neuropathic pain Mills, E.P. Di Pietro, Flavia Alshelh, Z. Peck, C.C. Murray, G.M. Vickers, E.R. Henderson, L.A. Science & Technology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology analgesia chronic pain locus ceruleus midbrain periaqueductal gray rostral ventromedial medulla spinal trigeminal nucleus SPINAL TRIGEMINAL NUCLEUS VENTROMEDIAL MEDULLA MAINTAINS NORADRENERGIC LOCUS-COERULEUS MIDBRAIN PERIAQUEDUCTAL GRAY NOXIOUS INHIBITORY CONTROLS DESCENDING FACILITATION DORSAL-HORN ANATOMICAL CHANGES RAT NEURONS © 2018 the authors. Preclinical investigations have suggested that altered functioning of brainstem pain-modulation circuits may be crucial for the maintenance of some chronic pain conditions. While some human psychophysical studies show that patients with chronic pain display altered pain-modulation efficacy, it remains unknown whether brainstem pain-modulation circuits are altered in individuals with chronic pain. The aim of the present investigation was to determine whether, in humans, chronic pain following nerve injury is associated with altered ongoing functioning of the brainstem descending modulation systems. Using resting-state functional magnetic resonance imaging, we found that male and female patients with chronic neuropathic orofacial pain show increased functional connectivity between the rostral ventromedial medulla (RVM) and other brainstem pain-modulatory regions, including the ventrolateral periaqueductal gray (vlPAG) and locus ceruleus (LC). We also identified an increase in RVM functional connectivity with the region that receives orofacial nociceptor afferents, the spinal trigeminal nucleus. In addition, the vlPAG and LC displayed increased functional connectivity strengths with higher brain regions, including the hippocampus, nucleus accumbens, and anterior cingulate cortex, in individuals with chronic pain. These data reveal that chronic pain is associated with altered ongoing functioning within the endogenous pain-modulation network. These changes may underlie enhanced descending facilitation of processing at the primary synapse, resulting in increased nociceptive transmission to higher brain centers. Further, our findings show that higher brain regions interact with the brainstem modulation system differently in chronic pain, possibly reflecting top–down engagement of the circuitry alongside altered reward processing in pain conditions. 2018 Journal Article http://hdl.handle.net/20.500.11937/79562 10.1523/JNEUROSCI.1647-17.2017 English http://purl.org/au-research/grants/nhmrc/1032072 http://purl.org/au-research/grants/nhmrc/1059182 http://creativecommons.org/licenses/by/4.0/ SOC NEUROSCIENCE fulltext |
| spellingShingle | Science & Technology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology analgesia chronic pain locus ceruleus midbrain periaqueductal gray rostral ventromedial medulla spinal trigeminal nucleus SPINAL TRIGEMINAL NUCLEUS VENTROMEDIAL MEDULLA MAINTAINS NORADRENERGIC LOCUS-COERULEUS MIDBRAIN PERIAQUEDUCTAL GRAY NOXIOUS INHIBITORY CONTROLS DESCENDING FACILITATION DORSAL-HORN ANATOMICAL CHANGES RAT NEURONS Mills, E.P. Di Pietro, Flavia Alshelh, Z. Peck, C.C. Murray, G.M. Vickers, E.R. Henderson, L.A. Brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| title | Brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| title_full | Brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| title_fullStr | Brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| title_full_unstemmed | Brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| title_short | Brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| title_sort | brainstem pain-control circuitry connectivity in chronic neuropathic pain |
| topic | Science & Technology Life Sciences & Biomedicine Neurosciences Neurosciences & Neurology analgesia chronic pain locus ceruleus midbrain periaqueductal gray rostral ventromedial medulla spinal trigeminal nucleus SPINAL TRIGEMINAL NUCLEUS VENTROMEDIAL MEDULLA MAINTAINS NORADRENERGIC LOCUS-COERULEUS MIDBRAIN PERIAQUEDUCTAL GRAY NOXIOUS INHIBITORY CONTROLS DESCENDING FACILITATION DORSAL-HORN ANATOMICAL CHANGES RAT NEURONS |
| url | http://purl.org/au-research/grants/nhmrc/1032072 http://purl.org/au-research/grants/nhmrc/1032072 http://hdl.handle.net/20.500.11937/79562 |