Periaqueductal gray

Animals face behavioral problems that can be conceptualized in terms of a gradient of spatial and temporal proximity. I propose that solving close-proximity behavioral problems involves integrating disparate types of information in complex and flexible ways. In this framework, the midbrain periaqueductal gray (PAG) is understood as a key region involved in close-proximity motivated cognition. Anatomically, the PAG has access to signals across the neuroaxis via extensive connectivity with cortex, subcortex, and brainstem...

Periaqueductal gray (PAG), an integration center for neuronal signals, is located in the midbrain and regulates multiple physiological and pathological behaviors, including pain, defensive and aggressive behaviors, anxiety and depression, cardiovascular response, respiration, and sleep-wake behaviors. Due to the different neuroanatomical connections and functional characteristics of the four functional columns of PAG, different subregions of PAG synergistically regulate various instinctual behaviors. In the current review, we summarized the role and possible neurobiological mechanism of different subregions of PAG in the regulation of pain, defensive and aggressive behaviors, anxiety, and depression from the perspective of the up-down neuronal circuits of PAG...

OBJECTIVES: To observe whether acupuncture up-regulates chemokine CXC ligand 1 (CXCL1) in the brain to play an analgesic role through CXCL1/chemokine CXC receptor 2 (CXCR2) signaling in adjuvant induced arthritis (AIA) rats, so as to reveal its neuro-immunological mechanism underlying improvement of AIA. METHODS: BALB/c mice with relatively stable thermal pain reaction were subjected to planta injection of complete Freund adjuvant (CFA) for establishing AIA model, followed by dividing the AIA mice into simple AF750 (fluorochrome) and AF750+CXCL1 groups ( n =2 in each group)...

Evidence suggests that insulin resistance plays an important role in developing diabetes complications. The association between insulin resistance and pain perception is less well understood. This study aimed to investigate the effects of peripheral insulin deficiency on pain pathways in the brain. Diabetes was induced in 60 male rats with streptozotocin (STZ). Insulin was injected into the left ventricle of the brain by intracerebroventricular (ICV) injection, then pain was induced by subcutaneous injection of 2...

BACKGROUND: Primary dysmenorrhea (PDM) is the most common problem in menstruating women. A number of functional magnetic resonance imaging (fMRI) study have revealed that the brain plays a crucial role in the pathophysiology of PDM. However, these results have been inconsistent, and there is a lack of a comprehensive fMRI study to clarify the onset and long-term effects of PDM. The aim of this study was thus to investigate the onset and long-term effects of PDM in a cohort of patients with PDM...

Neuropathic pain (NP) is a prevalent condition often associated with heightened pain responsiveness suggestive of central sensitization. Neuroimaging biomarkers of treatment outcomes may help develop personalised treatment strategies, but white matter (WM) properties have been under-explored for this purpose. Here we assessed whether WM pathways of the default mode network (DMN: medial prefrontal cortex (mPFC), posterior cingulate cortex (PCC), precuneus (PCu)) 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...

Stress-induced hyperalgesia (SIH) is induced by repeated or chronic exposure to stressful or uncomfortable environments. However, the neural mechanisms involved in the modulatory effects of the periaqueductal gray (PAG) and its associated loops on SIH development hav e not been elucidated. In the present study, we used chronic restraint stress (CRS)-induced hyperalgesia as a SIH model and manipulated neuronal activity via a pharmacogenetic approach to investigate the neural mechanism underlying the effects of descending pain-modulatory pathways on SIH...

BACKGROUND: Multiple sclerosis (MS) is the most common immune-mediated inflammatory disease of the central nervous system. It is characterized by symptoms such as visual disturbances, paresis with spasticity, paresthesia, numbness, and fatigue. However, several studies have shown a high prevalence of headaches in individuals with MS. Migraine and tension-type headaches are the most frequent types of headaches experienced by those with MS. Additionally, the role of MS disease-modifying agents must be considered...

OBJECTIVE: To investigate the role of glutamatergic neurons in the dorsomedial periaqueductal grey (dmPAG) in regulating excessive defensive behaviors in mice with post-traumatic stress disorder (PTSD). METHODS: Eight-week-old male C57BL/6 mice were subjected to stereotactic injections of different recombinant adeno- associated viral vectors (rAAV2/9-CaMKII-mCherry, rAAV2/9-CaMKII-hM3Dq-mCherry and rAAV2/9-CaMKII-hM4Di-mCherry) into the bilateral dmPAG for chemogenetic activation or inhibition of the glutamatergic neurons, followed 2 weeks later by PTSD modeling by single prolonged stress...

Traumatic Brain Injury (TBI) patients frequently experience chronic pain that can enhance their suffering and significantly impair rehabilitative efforts. Clinical studies suggest that damage to the periaqueductal grey matter (PAG) following TBI, a principal center involved in endogenous pain control, may underlie the development of chronic pain. We hypothesized that TBI would diminish the usual pain control functions of the PAG, but that directly stimulating this center using a chemogenetic approach would restore descending pain modulation...

INTRODUCTION: Migraine is a common clinical disorder, ranks as the second most disabling disease worldwide, and often manifests with unilateral onset. Contralateral acupuncture (CAT), as a classical acupuncture method, has been proven to be effective in the treatment of migraine without aura (MWoA). However, its neural mechanisms have not been investigated using multimodal magnetic resonance imaging (MRI). METHODS AND ANALYSIS: In this multimodal neuroimaging randomized trial, a total of 96 female MWoA participants and 30 female healthy controls (HCs) will be recruited...

Pavlovian fear conditioning research suggests that the interaction between the dorsal periaqueductal gray (dPAG) and basolateral amygdala (BLA) acts as a prediction error mechanism in the formation of associative fear memories. However, their roles in responding to naturalistic predatory threats, characterized by less explicit cues and the absence of reiterative trial-and-error learning events, remain unexplored. In this study, we conducted single-unit recordings in rats during an 'approach food-avoid predator' task, focusing on the responsiveness of dPAG and BLA neurons to a looming robot predator...

Cardiac pain is an index of cardiac ischemia that helps the detection of cardiac hypoxia and adjustment of activity in the sufferer. Drivers and thresholds of cardiac pain markedly differ in different subjects and can oscillate in the same individual, showing a distinct circadian rhythmicity and clinical picture. In patients with syndrome X or silent ischemia, cardiac pain intensity may cause neurogenic stress that potentiates the cardiac work and intensifies the cardiac hypoxia and discomfort of the patient...

The social dynamics of vocal behavior has major implications for social development in humans. We asked whether early life damage to the anterior cingulate cortex (ACC), which is closely associated with socioemotional regulation more broadly, impacts the normal development of vocal expression. The common marmoset provides a unique opportunity to study the developmental trajectory of vocal behavior, and to track the consequences of early brain damage on aspects of social vocalizations. We created ACC lesions in neonatal marmosets and compared their pattern of vocalization to that of age-matched controls throughout the first 6 weeks of life...

Cognitive reappraisal is fundamental to cognitive therapies and everyday emotion regulation. Analyses using Bayes factors and an axiomatic systems identification approach identified four reappraisal-related components encompassing distributed neural activity patterns across two independent functional magnetic resonance imaging (fMRI) studies (n = 182 and n = 176): (1) an anterior prefrontal system selectively involved in cognitive reappraisal; (2) a fronto-parietal-insular system engaged by both reappraisal and emotion generation, demonstrating a general role in appraisal; (3) a largely subcortical system activated during negative emotion generation but unaffected by reappraisal, including amygdala, hypothalamus and periaqueductal gray; and (4) a posterior cortical system of negative emotion-related regions downregulated by reappraisal...

OBJECTIVES: The new daily persistent headache (NDPH) is a rare primary headache disorder. However, the underlying mechanisms of NDPH remain incompletely understood. This study aims to apply seed-based analysis to explore the functional connectivity (FC) of brainstem nuclei in patients with NDPH using resting-state functional magnetic resonance imaging (MRI). METHODS: The FC analysis from the region of interest (ROI) to whole brain voxels was used to investigate 29 patients with NDPH and 37 well-matched healthy controls (HCs) with 3...

The periaqueductal gray (PAG) is located in the mesencephalon in the upper brainstem and, as part of the descending pain modulation, is considered a crucial structure for pain control. Its modulatory effect on painful sensation is often seen as a systemic function affecting the whole body similarly. However, recent animal data suggest some kind of somatotopy in the PAG. This would make the PAG capable of dermatome-specific analgesic function. We electrically stimulated the three peripheral dermatomes of the trigemino-cervical complex and the greater occipital nerve in 61 humans during optimized brainstem functional magnetic resonance imaging...

In neurodegenerative diseases, particularly in Parkinson's disease (PD), antinociceptive centers are often implicated in neurodegeneration, leading to persistent pain unresponsive to narcotic substances. This study investigated the periaqueductal gray matter (PAG) and the nucleus raphe magnus (NRM), components of the brain's antinociceptive system. In conditions of rotenone intoxication (an experimental PD model), morphological changes in intracellular structures were observed in PAG and NRM neurons, indicating metabolic disorders characteristic of PD (alterations in the shape and size of neuronal bodies and processes, disruption of acid phosphatase activity in neuron cytoplasm)...

Vocalization, a means of social communication, is prevalent among many species, including humans. Both rats and mice use ultrasonic vocalizations (USVs) in various social contexts and affective states. The motor cortex is hypothesized to be involved in precisely controlling USVs through connections with critical regions of the brain for vocalization, such as the periaqueductal grey matter (PAG). However, it is unclear how neurons in the motor cortex are modulated during USVs. Moreover, the relationship between USV modulation of neurons and anatomical connections from the motor cortex to PAG is also not clearly understood...

OBJECTIVE: This study investigated how high-definition transcranial direct current stimulation (HD-tDCS) over the primary motor cortex (M1) affects brain signal variability and functional connectivity in the trigeminal pain pathway, and their association with changes in migraine attacks. METHODS: Twenty-five episodic migraine patients were randomized for ten daily sessions of active or sham M1 HD-tDCS. Resting-state blood-oxygenation-level-dependent (BOLD) signal variability and seed-based functional connectivity were assessed pre- and post-treatment...