A fundamental issue in neuroscience is a lack of understanding regarding the relationship between brain function and the white matter architecture that supports it. Individuals with chronic neuropathic pain (NP) exhibit functional abnormalities throughout brain networks collectively termed the "dynamic pain connectome" (DPC), including the default mode network (DMN), salience network, and ascending nociceptive and descending pain modulation systems. These functional abnormalities are often observed in a sex-dependent fashion.
View Article and Find Full Text PDFThe perception of pain and ability to cope with it varies widely amongst people, which in part could be due to the presence of inhibitory (antinociceptive) or facilitatory (pronociceptive) effects in conditioned pain modulation (CPM). This study examined whether individual differences in CPM reflect functional connectivity (FC) strengths within nodes of the descending antinociceptive pathway (DAP). A heat-based CPM paradigm and resting-state functional magnetic resonance imaging (rs-fMRI) were used to test the hypothesis that an individual's capacity to exhibit inhibitory CPM (changes in test stimuli [TS] pain due to a conditioning stimulus [CS]) reflects FC of the subgenual anterior cingulate cortex (sgACC), periaqueductal gray (PAG), and rostral ventromedial medulla (RVM).
View Article and Find Full Text PDFChronic neuropathic pain can result from nervous system injury and can persist in the absence of external stimuli. Although ongoing pain characterizes the disorder, in many individuals, the intensity of this ongoing pain fluctuates dramatically. Previously, it was identified that functional magnetic resonance imaging signal covariations between the midbrain periaqueductal gray (PAG) matter, rostral ventromedial medulla (RVM), and spinal trigeminal nucleus are associated with moment-to-moment fluctuations in pain intensity in individuals with painful trigeminal neuropathy (PTN).
View Article and Find Full Text PDFNeuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalized treatment strategies, but white matter (WM) properties have been underexplored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex [mPFC], posterior cingulate cortex, and precuneus) and descending pain modulation system (periaqueductal gray [PAG]) are associated with ketamine analgesia and attenuated temporal summation of pain (TSP, reflecting central sensitization) in NP.
View Article and Find Full Text PDFPrior experiences, conditioning cues, and expectations of improvement are essential for placebo analgesia expression. The dorsolateral prefrontal cortex is considered a key region for converting these factors into placebo responses. Since dorsolateral prefrontal cortex neuromodulation can attenuate or amplify placebo, we sought to investigate dorsolateral prefrontal cortex biochemistry and function in 38 healthy individuals during placebo analgesia.
View Article and Find Full Text PDFConditioned pain modulation (CPM) is a physiological measure thought to reflect an individual's endogenous pain modulation system. CPM varies across individuals and provides insight into chronic pain pathophysiology. There is growing evidence that CPM may help predict individual pain treatment outcome.
View Article and Find Full Text PDFAcute pain serves as a protective mechanism that alerts us to potential tissue damage and drives a behavioural response that removes us from danger. The neural circuitry critical for mounting this behavioural response is situated within the brainstem and is also crucial for producing analgesic and hyperalgesic responses. In particular, the periaqueductal grey, rostral ventromedial medulla, locus coeruleus and subnucleus reticularis dorsalis are important structures that directly or indirectly modulate nociceptive transmission at the primary nociceptive synapse.
View Article and Find Full Text PDFPain perception can be powerfully influenced by an individual's expectations and beliefs. Although the cortical circuitry responsible for pain modulation has been thoroughly investigated, the brainstem pathways involved in the modulatory phenomena of placebo analgesia and nocebo hyperalgesia remain to be directly addressed. This study used ultra-high-field 7 tesla functional MRI (fMRI) to accurately resolve differences in brainstem circuitry present during the generation of placebo analgesia and nocebo hyperalgesia in healthy human participants ( = 25, 12 male).
View Article and Find Full Text PDFBackground: Chronic pain, particularly that following nerve injury, can occur in the absence of external stimuli. Although the ongoing pain is sometimes continuous, in many individuals the intensity of their pain fluctuates. Experimental animal studies have shown that the brainstem contains circuits that modulate nociceptive information at the primary afferent synapse and these circuits are involved in maintaining ongoing continuous neuropathic pain.
View Article and Find Full Text PDFThere is evidence from preclinical models of chronic pain and human psychophysical investigations to suggest that alterations in endogenous brainstem pain-modulation circuit functioning are critical for the initiation and/or maintenance of pain. Whilst preclinical models have begun to explore the functioning of this circuitry in chronic pain, little is known about such functioning in humans with chronic pain. The aim of this investigation was to determine whether individuals with chronic non-neuropathic pain, painful temporomandibular disorders (TMD), display alterations in brainstem pain-modulating circuits.
View Article and Find Full Text PDFPain is a complex phenomenon that is highly modifiable by expectation. Whilst the intensity of incoming noxious information plays a key role in the intensity of perceived pain, this intensity can be profoundly shaped by an individual's expectations. Modern brain imaging investigations have begun to detail the brain regions responsible for placebo and nocebo related changes in pain, but less is known about the neural basis of stimulus-expectancy changes in pain processing.
View Article and Find Full Text PDFChronic neuropathic pain (NP) is a complex disease that results from damage or presumed damage to the somatosensory nervous system. Current treatment regimens are often ineffective. The major impediment in developing effective treatments is our limited understanding of the underlying mechanisms.
View Article and Find Full Text PDFThe neural mechanism responsible for migraine remains unclear. While an external trigger has been proposed to initiate a migraine, it has also been proposed that changes in brainstem function are critical for migraine headache initiation and maintenance. Although the idea of altered brainstem function has some indirect support, no study has directly measured brainstem pain modulation circuitry function in migraineurs particularly immediately before a migraine.
View Article and Find Full Text PDFPreclinical 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.
View Article and Find Full Text PDF© LitMetric 2025. All rights reserved.