Retina nociceptor,as a key sensory receptor,not only enables the transport of warning signals to the human central nervous system upon its exposure to noxious stimuli,but also triggers the motor response that minimize...Retina nociceptor,as a key sensory receptor,not only enables the transport of warning signals to the human central nervous system upon its exposure to noxious stimuli,but also triggers the motor response that minimizes potential sensitization.In this study,the capability of two-dimensional all-oxide-heterostructured artificial nociceptor as a single device with tunable properties was confirmed.Newly designed nociceptors utilize ultra-thin sub-stoichiometric TiO2–Ga2O3 heterostructures,where the thermally annealed Ga2O3 films play the role of charge transfer controlling component.It is discovered that the phase transformation in Ga2O3 is accompanied by substantial jump in conductivity,induced by thermally assisted internal redox reaction of Ga2O3 nanostructure during annealing.It is also experimentally confirmed that the charge transfer in alloxide heterostructures can be tuned and controlled by the heterointerfaces manipulation.Results demonstrate that the engineering of heterointerfaces of two-dimensional(2D)films enables the fabrication of either high-sensitive TiO2–Ga2O3(Ar)or high-threshold TiO2–Ga2O3(N2)nociceptors.The hypersensitive nociceptor mimics the functionalities of corneal nociceptors of human eye,whereas the delayed reaction of nociceptor is similar to high-threshold nociceptive characteristics of human sensory system.The long-term stability of 2D nociceptors demonstrates the capability of heterointerfaces engineering for e ective control of charge transfer at 2D heterostructured devices.展开更多
We consider the problem of inducing withdrawal reflex on a test subject by exposing the subject’s skin to an electromagnetic beam. Heat-sensitive nociceptors in the skin are activated wherever the temperature is abov...We consider the problem of inducing withdrawal reflex on a test subject by exposing the subject’s skin to an electromagnetic beam. Heat-sensitive nociceptors in the skin are activated wherever the temperature is above the activation temperature. Withdrawal reflex occurs when the activated volume reaches a threshold. Previously we studied static beams with 3 types of power density distribution: Gaussian, super-Gaussian, and flat-top. We found that the flaptop is the best and the Gaussian is the worst in their performance with regard to 1) minimizing the time to withdrawal reflex, 2) minimizing the energy consumption and 3) minimizing the maximum temperature increase. The less-than-desirable performance of Gaussian beams is attributed to the uneven distribution of power density resulting in low energy efficiency: near the beam center the high power density does not contribute proportionally to increasing the activated volume;outside the beam effective radius the low power density fails to activate nociceptors. To overcome the drawbacks of Gaussian beams, in this study, we revolve a Gaussian beam around a fixed point to make the power density more uniformly distributed. We optimize the performance over two parameters: the spot size of static beam and the radius of beam revolution. We find that in comparison with a static Gaussian beam, a revolving Gaussian beam can reduce the energy consumption, and at the same time lower the maximum temperature.展开更多
Previously we introduced a concise dose-response model for the heat-induced withdrawal reflex caused by millimeter wave radiation. The model predicts the occurrence of withdrawal reflex from the given spatial temperat...Previously we introduced a concise dose-response model for the heat-induced withdrawal reflex caused by millimeter wave radiation. The model predicts the occurrence of withdrawal reflex from the given spatial temperature profile. It was formulated on the assumption that the density of nociceptors in skin is uniform, independent of the depth. The model has only two parameters: the activation temperature of heat-sensitive nociceptors and the critical threshold on the activated volume for triggering withdrawal reflex. In this study, we consider the case of depth-dependent nociceptor density in skin. We use a general parametric form with a scaling parameter in the depth direction to represent the nociceptor density. We analyze system behaviors for four density types of this form. Based on the theoretical results, we develop a methodology for 1) identifying from test data the density form of nociceptors distribution, 2) finding from test data the scaling parameter in the density form, and 3) determining from test data the activation temperature of nociceptors.展开更多
It is crucial to develop an advanced artificially intelligent optoelectronic information system that accurately simulates photonic nociceptors like the activation process of a human visual nociceptive pathway.Visible ...It is crucial to develop an advanced artificially intelligent optoelectronic information system that accurately simulates photonic nociceptors like the activation process of a human visual nociceptive pathway.Visible light reaches the retina for human visual perception,but its excessive exposure can damage nearby tissues.However,there are relatively few reports on visible light–triggered nociceptors.Here,we introduce a two-dimensional natural defectiveⅢ–Ⅵsemiconductorβ-In_(2)S_(3)and utilize its broad spectral response,including visible light brought by intrinsic defects,for visible light–triggered artificial photonic nociceptors.The response mode of the device,under visible light excitation,is very similar to that of the human eye.It perfectly reproduces the pain perception characteristics of the human visual system,such as‘threshold,’‘relaxation,’‘no adaptation’,and‘sensitization’.Its working principle is attributed to the mechanism of charge trapping associated with the intrinsic vacancies in In_(2)S_(3)nanosheets.This work provides an attractive material system(intrinsic defective semiconductors)for broadband artificial photonic nociceptors.展开更多
Topical irritants such as capsaicin(CAP),peppermint oil(PO),and mustard oil(MO)are effective in relieving inflammatory muscle pain.We investigated the effects of topical irritants in a rat model of inflammatory muscle...Topical irritants such as capsaicin(CAP),peppermint oil(PO),and mustard oil(MO)are effective in relieving inflammatory muscle pain.We investigated the effects of topical irritants in a rat model of inflammatory muscle pain produced by injecting complete Freund's adjuvant(CFA)into the tibialis anterior muscle.CFAinduced mechanical hypersensitivity and the spontaneous activity of muscular nociceptive afferents,and decreased weight-bearing of the hindlimb were relieved by topical application of CAP,PO,or MO on the skin overlying the inflamed muscle.The effects of topical irritants were abolished when applied to the skin on the ipsilateral plantar region or on the contralateral leg,or when the relevant cutaneous nerve or dorsal root was transected.Our results demonstrated that topical irritants may alleviate inflammatory muscle pain via activating cutaneous nociceptors and subsequently inhibiting the abnormal activity of muscular nociceptive neurons.展开更多
Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(...Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(Npy2 r)and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD.However,the molecular programs controlling their development are only beginning to be understood.Here we demonstrate that Npy2 r-expressing sensory neurons are in fact divided into two groups,based on transient or persistent Npy2 r expression.Npy2 r-transient neurons are myelinated,likely including A-fiber nociceptors,whereas Npy2 r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb.We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2 r-transient A-fiber nociceptors and MrgprD^+C-fiber nociceptors,respectively.Behaviorally,mice with conditional knockout of Nfia,but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses.Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.展开更多
Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being rel...Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise,among others, noradrenergic, serotonergic, γ-aminobutyric acid(GABA)ergic, and dopaminergic fibers.The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood.The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.展开更多
We consider the problem of inducing withdrawal reflex on a test subject by exposing the subject’s skin to an electromagnetic beam. Heat-sensitive nociceptors in the skin are activated wherever the temperature is abov...We consider the problem of inducing withdrawal reflex on a test subject by exposing the subject’s skin to an electromagnetic beam. Heat-sensitive nociceptors in the skin are activated wherever the temperature is above the activation temperature. Withdrawal reflex occurs when the activated volume reaches a threshold. We non-dimensionalize the problem to write the temperature as the product of a parameter-free function of non-dimensional variables and a function of beam parameters. This formulation allows studying beam parameters without knowing skin material parameters. We examine the effects of spot size, total power and distribution type of the electromagnetic beam on 3 quantities at reflex: 1) the time to reflex, 2) the maximum temperature increase, and 3) the total energy consumption. We find that the flat-top beam is the best, with the lowest energy consumption and the smallest maximum temperature increase. The Super-Gaussian beam is only slightly inferior to the flat-top. The Gaussian beam has by far the worst performance among these three.展开更多
Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment...Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.展开更多
基金supported by Research and Development Program of the Ghent University Global Campus,South Korea.
文摘Retina nociceptor,as a key sensory receptor,not only enables the transport of warning signals to the human central nervous system upon its exposure to noxious stimuli,but also triggers the motor response that minimizes potential sensitization.In this study,the capability of two-dimensional all-oxide-heterostructured artificial nociceptor as a single device with tunable properties was confirmed.Newly designed nociceptors utilize ultra-thin sub-stoichiometric TiO2–Ga2O3 heterostructures,where the thermally annealed Ga2O3 films play the role of charge transfer controlling component.It is discovered that the phase transformation in Ga2O3 is accompanied by substantial jump in conductivity,induced by thermally assisted internal redox reaction of Ga2O3 nanostructure during annealing.It is also experimentally confirmed that the charge transfer in alloxide heterostructures can be tuned and controlled by the heterointerfaces manipulation.Results demonstrate that the engineering of heterointerfaces of two-dimensional(2D)films enables the fabrication of either high-sensitive TiO2–Ga2O3(Ar)or high-threshold TiO2–Ga2O3(N2)nociceptors.The hypersensitive nociceptor mimics the functionalities of corneal nociceptors of human eye,whereas the delayed reaction of nociceptor is similar to high-threshold nociceptive characteristics of human sensory system.The long-term stability of 2D nociceptors demonstrates the capability of heterointerfaces engineering for e ective control of charge transfer at 2D heterostructured devices.
文摘We consider the problem of inducing withdrawal reflex on a test subject by exposing the subject’s skin to an electromagnetic beam. Heat-sensitive nociceptors in the skin are activated wherever the temperature is above the activation temperature. Withdrawal reflex occurs when the activated volume reaches a threshold. Previously we studied static beams with 3 types of power density distribution: Gaussian, super-Gaussian, and flat-top. We found that the flaptop is the best and the Gaussian is the worst in their performance with regard to 1) minimizing the time to withdrawal reflex, 2) minimizing the energy consumption and 3) minimizing the maximum temperature increase. The less-than-desirable performance of Gaussian beams is attributed to the uneven distribution of power density resulting in low energy efficiency: near the beam center the high power density does not contribute proportionally to increasing the activated volume;outside the beam effective radius the low power density fails to activate nociceptors. To overcome the drawbacks of Gaussian beams, in this study, we revolve a Gaussian beam around a fixed point to make the power density more uniformly distributed. We optimize the performance over two parameters: the spot size of static beam and the radius of beam revolution. We find that in comparison with a static Gaussian beam, a revolving Gaussian beam can reduce the energy consumption, and at the same time lower the maximum temperature.
文摘Previously we introduced a concise dose-response model for the heat-induced withdrawal reflex caused by millimeter wave radiation. The model predicts the occurrence of withdrawal reflex from the given spatial temperature profile. It was formulated on the assumption that the density of nociceptors in skin is uniform, independent of the depth. The model has only two parameters: the activation temperature of heat-sensitive nociceptors and the critical threshold on the activated volume for triggering withdrawal reflex. In this study, we consider the case of depth-dependent nociceptor density in skin. We use a general parametric form with a scaling parameter in the depth direction to represent the nociceptor density. We analyze system behaviors for four density types of this form. Based on the theoretical results, we develop a methodology for 1) identifying from test data the density form of nociceptors distribution, 2) finding from test data the scaling parameter in the density form, and 3) determining from test data the activation temperature of nociceptors.
基金the National Key Research and Development Program of China(2022YFB3505301)the National Natural Science Foundation of China(12174237,12241403 and 52002232).
文摘It is crucial to develop an advanced artificially intelligent optoelectronic information system that accurately simulates photonic nociceptors like the activation process of a human visual nociceptive pathway.Visible light reaches the retina for human visual perception,but its excessive exposure can damage nearby tissues.However,there are relatively few reports on visible light–triggered nociceptors.Here,we introduce a two-dimensional natural defectiveⅢ–Ⅵsemiconductorβ-In_(2)S_(3)and utilize its broad spectral response,including visible light brought by intrinsic defects,for visible light–triggered artificial photonic nociceptors.The response mode of the device,under visible light excitation,is very similar to that of the human eye.It perfectly reproduces the pain perception characteristics of the human visual system,such as‘threshold,’‘relaxation,’‘no adaptation’,and‘sensitization’.Its working principle is attributed to the mechanism of charge trapping associated with the intrinsic vacancies in In_(2)S_(3)nanosheets.This work provides an attractive material system(intrinsic defective semiconductors)for broadband artificial photonic nociceptors.
基金We thank Bo Yuan and Tao Wang from the Institute of Basic Medical Sciences,Chinese Academy of Medical Sciences,Beijing,China,for technical assistance.This work was supported by the National Natural Science Foundation of China(81771205,91632113)the Natural Science Foundation and Major Basic Research Program of Shanghai Municipality,China(16JC1420500 and 16JC1420502)+1 种基金the Chinese Academy of Medical Sciences Innovation Fund for Medical Sciences(2017-I2M-3-008)the National Natural Science Foundation for Young Scientists of China(81600956).
文摘Topical irritants such as capsaicin(CAP),peppermint oil(PO),and mustard oil(MO)are effective in relieving inflammatory muscle pain.We investigated the effects of topical irritants in a rat model of inflammatory muscle pain produced by injecting complete Freund's adjuvant(CFA)into the tibialis anterior muscle.CFAinduced mechanical hypersensitivity and the spontaneous activity of muscular nociceptive afferents,and decreased weight-bearing of the hindlimb were relieved by topical application of CAP,PO,or MO on the skin overlying the inflamed muscle.The effects of topical irritants were abolished when applied to the skin on the ipsilateral plantar region or on the contralateral leg,or when the relevant cutaneous nerve or dorsal root was transected.Our results demonstrated that topical irritants may alleviate inflammatory muscle pain via activating cutaneous nociceptors and subsequently inhibiting the abnormal activity of muscular nociceptive neurons.
基金supported by the National Natural Science Foundation of China (31771621,31171071 and 31671093)the Research Foundation for Advanced Talents from Hangzhou Normal University and the New York State Stem Cell Science contracts C026429 and C030133。
文摘Noxious mechanical information is transmitted through molecularly distinct nociceptors,with pinprickevoked sharp sensitivity via A-fiber nociceptors marked by developmental expression of the neuropeptide Y receptor 2(Npy2 r)and von Frey filament-evoked punctate pressure information via unmyelinated C fiber nociceptors marked by MrgprD.However,the molecular programs controlling their development are only beginning to be understood.Here we demonstrate that Npy2 r-expressing sensory neurons are in fact divided into two groups,based on transient or persistent Npy2 r expression.Npy2 r-transient neurons are myelinated,likely including A-fiber nociceptors,whereas Npy2 r-persistent ones belong to unmyelinated pruriceptors that co-express Nppb.We then showed that the transcription factors NFIA and Runx1 are necessary for the development of Npy2 r-transient A-fiber nociceptors and MrgprD^+C-fiber nociceptors,respectively.Behaviorally,mice with conditional knockout of Nfia,but not Runx1 showed a marked attenuation of pinprick-evoked nocifensive responses.Our studies therefore identify a transcription factor controlling the development of myelinated nociceptors.
基金supported by internal funds to MP from the Department of Anesthesiology,Stony Brook Medicine,USA
文摘Nociceptive signals conveyed to the dorsal horn of the spinal cord by primary nociceptors are subject to extensive modulation by local neurons and by supraspinal descending pathways to the spinal cord before being relayed to higher brain centers. Descending modulatory pathways to the spinal cord comprise,among others, noradrenergic, serotonergic, γ-aminobutyric acid(GABA)ergic, and dopaminergic fibers.The contributions of noradrenaline, serotonin, and GABA to pain modulation have been extensively investigated. In contrast, the contributions of dopamine to pain modulation remain poorly understood.The focus of this review is to summarize the current knowledge of the contributions of dopamine to pain modulation. Hypothalamic A11 dopaminergic neurons project to all levels of the spinal cord and provide the main source of spinal dopamine. Dopamine receptors are expressed in primary nociceptors as well as in spinal neurons located in different laminae in the dorsal horn of the spinal cord, suggesting that dopamine can modulate pain signals by acting at both presynaptic and postsynaptic targets. Here, I will review the literature on the effects of dopamine and dopamine receptor agonists/antagonists on the excitability of primary nociceptors, the effects of dopamine on the synaptic transmission between primary nociceptors and dorsal horn neurons, and the effects of dopamine on pain in rodents. Published data support both anti-nociceptive effects of dopamine mediated by D2-like receptors and pro-nociceptive effects mediated by D1-like receptors.
基金The project was supported by the Na-tional Natural Science Foundation of China(No.30371729,30400131)the Foundation of Education Ministry of China for Doctor Degree Candidate Training(20020698033,20040698022)the Shaanxi Province Natural Science Foundation of China(2004C225).
文摘We consider the problem of inducing withdrawal reflex on a test subject by exposing the subject’s skin to an electromagnetic beam. Heat-sensitive nociceptors in the skin are activated wherever the temperature is above the activation temperature. Withdrawal reflex occurs when the activated volume reaches a threshold. We non-dimensionalize the problem to write the temperature as the product of a parameter-free function of non-dimensional variables and a function of beam parameters. This formulation allows studying beam parameters without knowing skin material parameters. We examine the effects of spot size, total power and distribution type of the electromagnetic beam on 3 quantities at reflex: 1) the time to reflex, 2) the maximum temperature increase, and 3) the total energy consumption. We find that the flat-top beam is the best, with the lowest energy consumption and the smallest maximum temperature increase. The Super-Gaussian beam is only slightly inferior to the flat-top. The Gaussian beam has by far the worst performance among these three.
文摘Chronic musculoskeletal pain(CMP)is a common occurrence in clinical practice and there are a variety of options for the treatment of it.However,the pharmacological therapy is still considered to be a primary treatment.The recent years have witnessed the emergence of opioid crisis,yet there are no relevant guidelines on how to treat CMP with non-opioid analgesics properly.The Chinese Medical Association for the Study of Pain convened a panel meeting to develop clinical practice consensus for the treatment of CMP with non-opioid analgesics.The purpose of this consensus is to present the application of nonsteroidal antiinflammatory drugs,serotonin norepinephrine reuptake inhibitors,serotonin and norepinephrine reuptake inhibitors,muscle relaxants,ion channel drugs and topical drugs in CMP.
