vlPAG

The bed nucleus of the stria terminalis (BNST) plays an important role in feeding regulation through projections to other brain areas. However, whether functional distinctions exist within different BNST cells is not clear. Here, we found optogenetic activation of LH-projecting BNST neurons induced aversion and significantly reduced consumption of normal chow but not high-fat diets (HFD). In contrast, photoactivation of vlPAG-projecting BNST neurons induced place preference and promoted HFD intake, without affecting normal chow consumption...

Endogenous pain modulation in humans is frequently investigated with conditioned pain modulation (CPM). Deficient pain inhibition is a proposed mechanism that contributes to neuropathic pain (NP) after spinal cord injury (SCI). Recent studies have combined CPM testing and neuroimaging to reveal neural correlates of CPM efficiency in chronic pain. This study investigated differences in CPM efficiency in relation to resting-state functional connectivity (rsFC) between 12 SCI-NP subjects and 13 age- and sex-matched healthy controls (HC)...

Aversion refers to feelings of strong dislike or avoidance toward particular stimuli or situations. Aversion can be caused by pain stimuli and has a long-term negative impact on physical and mental health. Aversion can also be caused by drug abuse withdrawal, resulting in people with substance use disorder to relapse. However, the mechanisms underlying aversion remain unclear. The ventrolateral periaqueductal gray (vlPAG) is considered to play a key role in aversive behavior. Our study showed that inhibition of vlPAG GABAergic neurons significantly attenuated the conditioned place aversion (CPA) induced by hindpaw pain pinch or naloxone-precipitated morphine withdrawal...

Cannabinoid-targeted pain therapies are increasing with the expansion of cannabis legalization, however, their efficacy may be limited by pain-induced adaptations in the cannabinoid system. Cannabinoid receptor subtype 1 (CB1Rs) inhibition of spontaneous, miniature and evoked GABAergic postsynaptic currents (mIPSCs and eIPSCs) in the ventrolateral periaqueductal gray (vlPAG) were compared in slices from naïve and inflamed male and female Sprague-Dawley rats. Complete Freund's Adjuvant (CFA) injections into the hindpaw induced persistent inflammation...

Chronic pain conditions within clinical populations are correlated with a high incidence of depression, and researchers have reported their high rate of comorbidity. Clinically, chronic pain worsens the prevalence of depression, and depression increases the risk of chronic pain. Individuals suffering from chronic pain and depression respond poorly to available medications, and the mechanisms underlying the comorbidity of chronic pain and depression remain unknown. We used spinal nerve ligation (SNL) in a mouse model to induce comorbid pain and depression...

BACKGROUND: BTRX-246040, a nociceptin/orphanin FQ (N/OFQ) peptide (NOP) receptor antagonist, is being developed for the treatment of depressive patients. However, the underlying mechanism of this potential antidepressant is still largely unclear. Here, we studied the antidepressant-related actions of BTRX-246040 in the ventrolateral periaqueductal gray (vlPAG). METHODS: The tail suspension test (TST), forced swim test (FST), female urine sniffing test (FUST), sucrose preference test (SPT), and learned helplessness (LH) combined with pharmacological approaches were employed to examine the antidepressant-like effects and the drug effects on LH-induced depressive-like behavior in C57BL/6J mice...

INTRODUCTION: The extinction of fear memories is an important component in regulating defensive behaviors, contributing toward adaptive processes essential for survival. The cerebellar medial nucleus (MCN) has bidirectional connections with the ventrolateral periaqueductal gray (vlPAG) and is implicated in the regulation of multiple aspects of fear, such as conditioned fear learning and the expression of defensive motor outputs. However, it is unclear how communication between the MCN and vlPAG changes during conditioned fear extinction...

The midbrain periaqueductal gray (PAG), particularly its ventrolateral column (vlPAG), is part of a key descending pathway that modulates nociception, fear and anxiety behaviours in both humans and rodents. It has been previously demonstrated that inhibitory GABAergic neurons within the vlPAG have a major role in this nociceptive modulation. However, the PAG contains a diverse range of neuronal subtypes and the contribution of different subtypes of inhibitory neurons to nociceptive control has not been investigated...

The ventrolateral periaqueductal gray (vlPAG) is a key brain area within the descending pain modulatory pathway and an important target for opioid-induced analgesia. The vlPAG contains heterogeneous neurons with respect to neurotransmitter content, receptor and channel expression, and in vivo response to noxious stimuli. This study characterizes intrinsic membrane properties of vlPAG neurons to identify which neuron types respond to inflammation and determine whether the pain-responsive neurons are inhibited by opioids...

Itch and pain are two closely related sensations that receiving similar encodings at multiple levels. Accumulated evidences suggest that activation of the ventral lateral geniculate nucleus and intergeniculate leaflet (vLGN/IGL)-to-lateral and ventrolateral periaqueductal gray (l/vlPAG) projections mediates the antinociceptive effects of bright light therapy. Clinical study showed that bright light therapy may ameliorate cholestasis-induced pruritus. However, the underlying mechanism and whether this circuit participates in itch modulation remains unclear...

GOAL: We applied the method of non-invasive ultrasound (US) neuromodulation to regulate blood pressure (BP) by stimulating the solitary tract nucleus (NTS) of spontaneously hypertensive rats (SHRs). METHODS: The rats were exposed to US stimulation for 20 mins every day for two months. Morphology and function of the hypertensive target organs (heart and kidney) were then examined by echocardiography and immunohistochemical staining. C-fos immunofluorescence assays were used to evaluate neuronal activity in the US stimulated areas and to explore related neural pathways...

Postoperative cognitive dysfunction (POCD) is a medically induced, rapidly occurring postoperative disease, which is hard to recover and seriously threatens the quality of life, especially for elderly patients, so it is important to identify the risk factors for POCD and apply early intervention to prevent POCD. As we have known, pain can impair cognition, and many surgery patients experience different preoperative pain, but it is still unknown whether these patients are vulnerable for POCD. Here we found that chronic pain (7 days, but not 1 day acute pain) induced by Complete Freund's Adjuvant (CFA) injected in the hind paw of rats could easily induce spatial cognition and memory impairment after being exposed to sevoflurane anesthesia...

Chronic pain could cause both hyperalgesia and anxiety symptoms. How the two components are encoded in the brain remains unclear. The prelimbic cortex (PrL), a critical brain region for both nociceptive and emotional modulations, serves as an ideal medium for comparing the encoding of the two components. We report that PrL neurons projecting to the basolateral amygdala (PrLBLA) and those projecting to the ventrolateral periaqueductal gray (PrLl/vlPAG) were segregated and displayed elevated and reduced neuronal activity, respectively, during pain chronicity...

Abdominal pain in Crohn's disease (CD) has been known to be associated with changes in the central nervous system. The periaqueductal gray (PAG) plays a well-established role in pain processing. However, the role of PAG-related network and the effect of pain on the network in CD remain unclear.Resting-state functional magnetic imaging (fMRI) data were collected from 24 CD patients in remission with abdominal pain, 24 CD patients without abdominal pain and 28 healthy controls (HCs). Using the subregions of PAG (dorsomedial (dmPAG), dorsolateral (dlPAG), lateral (lPAG) and ventrolateral (vlPAG)) as seeds, the seed-based FC maps were calculated and one-way analysis of variance (ANOVA) was performed to investigate the differences among the three groups...

BACKGROUND: The analgesic effect of acupuncture is widely recognized, but the mechanical characteristics of acupuncture for pain relief, compared to non-steroidal anti-inflammatory (NSAIDs) and placebo medication, remain unknown. AIMS: To compare the modulation effects of acupuncture treatment with NSAIDs and placebo medication on descending pain modulation system (DPMS) in knee osteoarthritis (KOA) patients. METHODS: This study recruited 180 KOA patients with knee pain and 41 healthy controls (HCs)...

OBJECTIVE: In this study, we aimed to investigate the sustainable antihypertensive effects and protection against target organ damage caused by low-intensity focused ultrasound (LIFU) stimulation and the underlying mechanism in spontaneously hypertensive rats (SHRs) model. METHODS AND RESULTS: SHRs were treated with ultrasound stimulation of the ventrolateral periaqueductal gray (VlPAG) for 20 min every day for 2 months. Systolic blood pressure (SBP) was compared among normotensive Wistar-Kyoto rats, SHR control group, SHR Sham group, and SHR LIFU stimulation group...

The hypothalamic neuropeptide oxytocin (OT) exerts prominent analgesic effects via central and peripheral action. However, the precise analgesic pathways recruited by OT are largely elusive. Here we discovered a subset of OT neurons whose projections preferentially terminate on OT receptor (OTR)-expressing neurons in the ventrolateral periaqueductal gray (vlPAG). Using a newly generated line of transgenic rats (OTR-IRES-Cre), we determined that most of the vlPAG OTR expressing cells targeted by OT projections are GABAergic...

BACKGROUNDS: Botulinum toxin type A (BoNT/A) is extensively applied in spasticity and dystonia as it cleaves synaptosome-associated protein 25 (SNAP25) in the presynaptic terminals, thereby inhibiting neurotransmission. An increasing number of randomized clinical trials have suggested that glabellar BoNT/A injection improves depressive symptoms in patients with major depressive disorder (MDD). However, the underlying neuronal circuitry of BoNT/A-regulated depression remains largely uncharacterized...

Prenatal hypoxic-ischemic insult (HI) may lead to a variety of neurological consequences that may persist throughout adulthood. In the most severe cases, HI is known to increase pain sensitivity which profoundly impacts quality of life. Periaqueductal gray matter (PAG) is a relevant region of the descending pain pathway and its function may be modulated by a complex network that includes nitrergic neurons and glial response, among other factors. Astrocytes, central players in pain modulation, are known to respond to HI by inducing hyperplasia, hypertrophy and increasing the number of their processes and the staining of glial fibrillary acidic protein (GFAP)...

Posterior hypothalamus (PH), an important part of the descending pain processing pathway, has been found to be activated in trigeminal autonomic cephalalgias. However, there are very few studies conducted and information regarding its implications in trigeminal neuropathic pain (TNP). Therefore, we aimed to ascertain whether optogenetic inhibition of PH could affect the outcomes of a chronic constriction injury in the infraorbital nerve (CCI-ION) rat model. Animals were divided into the TNP animal, sham, and naive-control groups...