Gamma-band oscillations (GBOs) in the primary somatosensory cortex (S1) play key roles in nociceptive processing. Yet, one crucial question remains unaddressed: what neuronal mechanisms underlie nociceptive-evoked GBOs? Here, we addressed this question using a range of somatosensory stimuli (nociceptive and non-nociceptive), neural recording techniques (electroencephalography in humans and silicon probes and calcium imaging in rodents), and optogenetics (alone or simultaneously with electrophysiology in mice). We found that (1) GBOs encoded pain intensity independent of stimulus intensity in humans, (2) GBOs in S1 encoded pain intensity and were triggered by spiking of S1 interneurons, (3) parvalbumin (PV)-positive interneurons preferentially tracked pain intensity, and critically, (4) PV S1 interneurons causally modulated GBOs and pain-related behaviors for both thermal and mechanical pain.
View Article and Find Full Text PDFPeripheral optogenetics is an emerging neuromodulation technique that regulates the activity of the nervous system outside the brain through the expression of photosensitive proteins and the application of photic stimulation. This article reviews recent advances in applying optogenetics to the spinal cord and peripheral nerves, offering a comprehensive understanding of the functions and regulatory mechanisms of the peripheral nervous system through the modulation of specific neuronal activities. By showcasing novel opportunities for disease treatment, this technique opens new avenues in psychophysiological research and neural regulation therapy.
View Article and Find Full Text PDFThe absence of a comprehensive understanding of the neural basis of spontaneous pain limits the development of therapeutic strategies targeting this primary complaint of patients with chronic pain. Here we report a distinct neuronal ensemble within the prelimbic cortex which processes signals related to spontaneous pain in rats with chronic inflammatory pain. This neuronal ensemble specifically encodes spontaneous pain-related behaviors, independently of other locomotive and evoked behaviors.
View Article and Find Full Text PDFThe thalamus and its cortical connections play a pivotal role in pain information processing, yet the exploration of its electrophysiological responses to nociceptive stimuli has been limited. Here, in 2 experiments we recorded neural responses to nociceptive laser stimuli in the thalamic (ventral posterior lateral nucleus and medial dorsal nucleus) and cortical regions (primary somatosensory cortex [S1] and anterior cingulate cortex) within the lateral and medial pain pathways. We found remarkable similarities in laser-evoked brain responses that encoded pain intensity within thalamic and cortical regions.
View Article and Find Full Text PDFThe prelimbic cortex (PL) is actively engaged in pain modulation. The infralimbic cortex (IL) has been reported to regulate the PL. However, how this regulation affects pain remains unclear.
View Article and Find Full Text PDFSearching for pain-preferential neural activity is essential for understanding and managing pain. Here, we investigated the preferential role of thalamocortical neural dynamics in encoding pain using human neuroimaging and rat electrophysiology across three studies. In study 1, we found that painful stimuli preferentially activated the medial-dorsal (MD) thalamic nucleus and its functional connectivity with the dorsal anterior cingulate cortex (dACC) and insula in two human functional magnetic resonance imaging (fMRI) datasets (n = 399 and n = 25).
View Article and Find Full Text PDFNeurosci Bull
February 2024
As a main structure of the limbic system, the hippocampus plays a critical role in pain perception and chronicity. The ventral hippocampal CA1 (vCA1) is closely associated with negative emotions such as anxiety, stress, and fear, yet how vCA1 neurons encode nociceptive information remains unclear. Using in vivo electrophysiological recording, we characterized vCA1 pyramidal neuron subpopulations that exhibited inhibitory or excitatory responses to plantar stimuli and were implicated in encoding stimuli modalities in naïve rats.
View Article and Find Full Text PDFDeep brain stimulation (DBS) is a promising therapy for treatment-resistant depression, while mechanisms underlying its therapeutic effects remain poorly defined. Increasing evidence has revealed an intimate association between the lateral habenula (LHb) and major depression, and suggests that the LHb might be an effective target of DBS therapy for depression. Here, we found that DBS in the LHb effectively decreased depression-like behaviors in rats experienced with chronic unpredictable mild stress (CUMS), a well-accepted paradigm for modeling depression in rodents.
View Article and Find Full Text PDFIn this study, we aimed to evaluate the anti-inflammatory and anti-apoptotic effects of melatonin (MLT) on neuropathic pain (NP)-induced anxiety and depression in a rat model. Adult male rats were separated into four groups, i.e.
View Article and Find Full Text PDFThe investigation of neurophysiologic mechanisms of anesthetic drug-induced loss of consciousness (LOC) by using the entropy, complexity, and information integration theories at the mesoscopic level has been a hot topic in recent years. However, systematic research is still lacking.We analyzed electrocorticography (ECoG) data recorded from nine rats during isoflurane-induced unconsciousness.
View Article and Find Full Text PDFInt J Environ Res Public Health
February 2022
Humans have used opioids to suppress moderate to severe pain for thousands of years. However, the long-term use of opioids has several adverse effects, such as opioid tolerance, opioid-induced hyperalgesia, and addiction. In addition, the low efficiency of opioids in controlling neuropathic pain limits their clinical applications.
View Article and Find Full Text PDFQuantitative evaluation of analgesic efficacy improves understanding of the antinociceptive mechanisms of new analgesics and provides important guidance for their development. Lappaconitine (LA), a potent analgesic drug extracted from the root of natural Aconitum species, has been clinically used for years because of its effective analgesic and non-addictive properties. However, being limited to ethological experiments, previous studies have mainly investigated the analgesic effect of LA at the behavioral level, and the associated antinociceptive mechanisms are still unclear.
View Article and Find Full Text PDFEven with an improved understanding of pain mechanisms and advances in perioperative pain management, inadequately controlled postoperative pain remains. Predicting acute postoperative pain based on presurgery physiological measures could provide valuable insights into individualized, effective analgesic strategies, thus helping improve the analgesic efficacy. Considering the strong correlation between pain perception and neural oscillations, we hypothesize that acute postoperative pain could be predicted by neural oscillations measured shortly before the surgery.
View Article and Find Full Text PDFChronic pain is considered an economic burden on society as it often results in disability, job loss, and early retirement. Opioids are the most common analgesics prescribed for the management of moderate to severe pain. However, chronic exposure to these drugs can result in opioid tolerance and opioid-induced hyperalgesia.
View Article and Find Full Text PDFThe brain and the spinal cord together make up the central nervous system (CNS). The functions of the human brain have been the focus of neuroscience research for a long time. However, the spinal cord is largely ignored, and the functional interaction of these two parts of the CNS is only partly understood.
View Article and Find Full Text PDFGamma-band oscillations (GBOs) elicited by transient nociceptive stimuli are one of the most promising biomarkers of pain across species. Still, whether these GBOs reflect stimulus encoding in the primary somatosensory cortex (S1) or nocifensive behavior in the primary motor cortex (M1) is debated. Here we recorded neural activity simultaneously from the brain surface as well as at different depths of the bilateral S1/M1 in freely-moving male rats receiving nociceptive stimulation.
View Article and Find Full Text PDFPhospho-tau accumulation and adult hippocampal neurogenesis (AHN) impairment both contribute importantly to the cognitive decline in Alzheimer's disease (AD), but whether and how tau dysregulates AHN in AD remain poorly understood. Here, we found a prominent accumulation of phosphorylated tau in GABAergic interneurons in the dentate gyrus (DG) of AD patients and mice. Specific overexpression of human tau (hTau) in mice DG interneurons induced AHN deficits but increased neural stem cell-derived astrogliosis, associating with a downregulation of GABA and hyperactivation of neighboring excitatory neurons.
View Article and Find Full Text PDFPain involves an intrinsically dynamic connectome characterized by fluctuating spontaneous brain activity and continuous neuroplastic changes of relevant circuits. Activity in the hippocampus-medial prefrontal cortex (mPFC) pathway has been suggested to correlate with spontaneous pain and pain chronicity, but causal evidence is lacking. Here we combine longitudinal in vivo electrophysiological recording with behavioral testing and show that persistent spontaneous pain disrupts ventral hippocampal CA1-infralimbic cortex (vCA1-IL) connectivity and hippocampal modulation of IL neuronal activity in rats with peripheral inflammation.
View Article and Find Full Text PDFNeuroimaging studies have shown that the anterior cingulate cortex (ACC) is consistently activated by thirst and may underlie the affective motivation of drinking behaviour demanded by thirst. But direct evidence for this hypothesis is lacking. The present study evaluated potential correlations between ACC neuronal activity and drinking behaviour in rats injected with different concentrations of saline.
View Article and Find Full Text PDFResting state electroencephalography (EEG) during eyes-closed and eyes-open conditions is widely used to evaluate brain states of healthy populations and brain dysfunctions in clinical conditions. Although several results have been obtained by measuring these brain activities in humans, it remains unclear whether the same results can be replicated in animals, i.e.
View Article and Find Full Text PDFDecisional impulsivity is one of the risk factors for occurrence and development of many mental disorders, and that the dysfunctions of orbitofrontal cortex (OFC) and nucleus accumbens core (NAcC) are at least involved. Although previous studies have shown that the role of OFC as a whole in regulating decision-making impulse behavior is inconsistent, it's still unclear that the roles of the subregions of OFC including their projections to the NAcC in decisional impulsivity. The present study was designed to investigate the roles of OFC subregions, medial OFC (mOFC) and lateral OFC (lOFC) and their projections to the NAcC in decisional impulsivity in free-moving rats.
View Article and Find Full Text PDFElectrocortical responses, elicited by laser heat pulses that selectively activate nociceptive free nerve endings, are widely used in many animal and human studies to investigate the cortical processing of nociceptive information. These laser-evoked brain potentials (LEPs) consist of several transient responses that are time-locked to the onset of laser stimuli. However, the functional properties of the LEP responses are still largely unknown, due to the lack of a sampling technique that can simultaneously record neural activities at the surface of the cortex (i.
View Article and Find Full Text PDFIn chronic pain, it has been reported that the medial prefrontal cortex (mPFC) takes important regulatory roles, and may change functionally and morphologically in result of chronic pain. Brain-derived neurotrophic factor (BDNF) is well known as a critical modulator of neuronal excitability and synaptic transmission in the central nervous system. The aim of the present study is to investigate the role of BDNF in the infralimbic cortex and the prelimbic cortex of the mPFC in complete Freund's adjuvant (CFA)-induced inflammatory pain.
View Article and Find Full Text PDF