The 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.In the present study,we recorded t...The 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.In the present study,we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli,but a temporary hypofunction of the IL by in vivo electrophysiological recording in rats with peripheral inflammation.Manipulation of the PL or IL had opposite effects on thermal hyperalgesia.Furthermore,the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL.Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia,whereas its inhibition exacerbated chronic pain.Overall,our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain:hypo-function of the IL leads to hyperactivity of the PL,which regulates thermal hyperalgesia,and thus contributes to the chronicity of pain.展开更多
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...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.Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions:the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli,whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties.Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors.Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats,whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain.These results provide direct evidence for the representations of nociceptive information in vCA1.展开更多
Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a...Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia,where two different contexts(dark and bright) were matched with a high(52°C) or low(48°C) temperature in the hot-plate test during training. Before and after training,we set the temperature to the high level in both contexts.Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone(an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.展开更多
Spontaneous pain occurring without apparent external stimuli,is a significant complaint of individuals with chronic pain whose mechanisms,somewhat surprisingly,remain poorly understood.Over the past decades,neuroimagi...Spontaneous pain occurring without apparent external stimuli,is a significant complaint of individuals with chronic pain whose mechanisms,somewhat surprisingly,remain poorly understood.Over the past decades,neuroimaging studies start to reveal brain activities accompanying spontaneous pain.Meanwhile,a variety of animal models and behavioral tests have been established,including non-reflexive tests and free-choice tests,which have been shown to be effective in assessing spontaneous pain.For the spontaneous pain mechanisms,multiple lines of research mainly focus on three aspects:(1)sensitization of peripheral nociceptor receptors and ion channels,(2)spontaneous neuronal firing and abnormal activity patterns at the dorsal root ganglion and spinal cord level,(3)functional and structural alterations in the brain,particularly the limbic system and the medial pain pathway.Despite accumulating evidence revealing distinct neuronal mechanisms from evoked pain,we are still far from full understanding of spontaneous pain,leaving a big gap between bench and bedside for chronic pain treatment.A better understanding of the neural processes in chronic pain,with specific linkage as to which anatomical structures and molecules related to spontaneous pain perception and comorbidities,will greatly improve our ability to develop novel therapeutics.展开更多
基金supported by the National Natural Foundation of China(32371049,32271053,31872774,81974166,81821092,82101303,32271053,and 32000749)the Beijing Natural Science Foundation(L222016)+1 种基金the China Postdoctoral Science Foundation(2020M670061)the Tianjin Key Laboratory of Brain Science and Neuroengineering.
文摘The 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.In the present study,we recorded temporary hyper-activity of PL pyramidal neurons responding to nociceptive stimuli,but a temporary hypofunction of the IL by in vivo electrophysiological recording in rats with peripheral inflammation.Manipulation of the PL or IL had opposite effects on thermal hyperalgesia.Furthermore,the functional connectivity and chemogenetic regulation between the subregions indicated an inhibitory influence of the IL on the PL.Activation of the pathway from the IL to the PL alleviated thermal hyperalgesia,whereas its inhibition exacerbated chronic pain.Overall,our results suggest a new mechanism underlying the role of the medial prefrontal cortex in chronic pain:hypo-function of the IL leads to hyperactivity of the PL,which regulates thermal hyperalgesia,and thus contributes to the chronicity of pain.
基金supported by the National Natural Science Foundation of China(81974166,32271053,and 31872774).
文摘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.Functional heterogeneity of the vCA1 pyramidal neurons was further identified in neuropathic pain conditions:the proportion and magnitude of the inhibitory response neurons paralleled mechanical allodynia and contributed to the confounded encoding of innocuous and noxious stimuli,whereas the excitatory response neurons were still instrumental in the discrimination of stimulus properties.Increased theta power and theta-spike coupling in vCA1 correlated with nociceptive behaviors.Optogenetic inhibition of vCA1 pyramidal neurons induced mechanical allodynia in naïve rats,whereas chemogenetic reversal of the overall suppressed vCA1 activity had analgesic effects in rats with neuropathic pain.These results provide direct evidence for the representations of nociceptive information in vCA1.
基金supported by grants from the National Natural Science Foundation of China (91732107, 31200835, 81571067, and 81521063)the National Basic Research Development Program (973 Program) of China (2014CB548200 and 2015CB554503)
文摘Cognition and pain share common neural substrates and interact reciprocally: chronic pain compromises cognitive performance, whereas cognitive processes modulate pain perception. In the present study, we established a non-drug-dependent rat model of context-based analgesia,where two different contexts(dark and bright) were matched with a high(52°C) or low(48°C) temperature in the hot-plate test during training. Before and after training,we set the temperature to the high level in both contexts.Rats showed longer paw licking latencies in trials with the context originally matched to a low temperature than those to a high temperature, indicating successful establishment of a context-based analgesic effect in rats. This effect was blocked by intraperitoneal injection of naloxone(an opioid receptor antagonist) before the probe. The context-based analgesic effect also disappeared after optogenetic activation or inhibition of the bilateral infralimbic or prelimbic sub-region of the prefrontal cortex. In brief, we established a context-based, non-drug dependent, placebo-like analgesia model in the rat. This model provides a new and useful tool for investigating the cognitive modulation of pain.
基金supported by the National Natural Science Foundation of China(31872774,82101303,81974166,81821092)Beijing Natural Science Foundation(7202083,5182013)+1 种基金the Interdisciplinary Medicine Seed Fund of Peking University(BMU2018MX011)China Postdoctoral Science Foundation(2020M670061)。
文摘Spontaneous pain occurring without apparent external stimuli,is a significant complaint of individuals with chronic pain whose mechanisms,somewhat surprisingly,remain poorly understood.Over the past decades,neuroimaging studies start to reveal brain activities accompanying spontaneous pain.Meanwhile,a variety of animal models and behavioral tests have been established,including non-reflexive tests and free-choice tests,which have been shown to be effective in assessing spontaneous pain.For the spontaneous pain mechanisms,multiple lines of research mainly focus on three aspects:(1)sensitization of peripheral nociceptor receptors and ion channels,(2)spontaneous neuronal firing and abnormal activity patterns at the dorsal root ganglion and spinal cord level,(3)functional and structural alterations in the brain,particularly the limbic system and the medial pain pathway.Despite accumulating evidence revealing distinct neuronal mechanisms from evoked pain,we are still far from full understanding of spontaneous pain,leaving a big gap between bench and bedside for chronic pain treatment.A better understanding of the neural processes in chronic pain,with specific linkage as to which anatomical structures and molecules related to spontaneous pain perception and comorbidities,will greatly improve our ability to develop novel therapeutics.
