Electrolytic lesion of the nucleus raphe magnus reduced the antinociceptive effects of bilateral morphine microinjected into the nucleus cuneiformis in rats

Spinal and supraspinal processing of thermal stimuli: An fMRI study

“…Interestingly, we did not observe any activity in PAG or NCF during allodynia, which is in contrast to former fMRI studies investigating neuropathic pain and experimental pain states . The different findings could be either due to different experimental set ups (pain model, stimulus, MRI sequences, or devices) or due to simultaneous processes of activation and suppression during heat allodynia within the PAG and NCF, as they are thought to also facilitate painful stimuli by the suppression of their antinociceptive descending pathway .…”

“…On the level of the midbrain, the current literature proposes that PAG (8) and NCF (26,27) prevent excessive pain through a spinobulbospinal negative feedback loop with most of NCF's efferent fibers running ipsilaterally (28). Accordingly, this study shows activations in PAG and ipsilateral NCF during stimulation with noxious heat similar to former studies that have shown PAG-activations during thermal painful stimuli (13).…”

Hypoechogenicity of brainstem raphe nuclei is associated with increased attack frequency in episodic migraine

“…As known, PAG and NCI are densely connected to serotonergic raphe nuclei, forming an important part of the descending pain-modulatory pathway. Stereotactic interventions on PAG and dorsal nucleus raphe result in migraine attacks even in non-migraine patients (26–28). A radio ligand single-photon emission CT study revealed an increased availability of the serotonin transporter in the raphe nuclei, endorsing the biochemical theory of migraine as a “chronic low serotonin syndrome (5,29).…”

Interictal Dysfunction of a Brainstem Descending Modulatory Center in Migraine Patients

“…Additionally, electrical stimulation or microinjection of morphine into NCF in the rat can also activate glutamatergic projections to the NRM, leading to modulation of pain-related behaviors [10], [13]. In addition to the NCF-NRM pathway, recent evidence suggests that morphine microinjection into NCF may activate a compensatory descending modulatory pathway when the NRM is lesioned [12]. Human imaging studies have reported that activations in NCF and the rostroventral medulla are correlated during repeated noxious stimulation [14], and also that NCF may activate during punctate mechanical hyperalgesia, suggesting that it is involved in a alterations in descending pain modulation [16].…”