Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of v...Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.展开更多
Autonomic dysreflexia （AD） is a serious cardiovascular disorder in patients with spinal cord injury （SCI）. The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons ...Autonomic dysreflexia （AD） is a serious cardiovascular disorder in patients with spinal cord injury （SCI）. The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons （SPNs） caudal to the injury, which renders the SPNs hyper-responsive to stimulation. Central maladaptive plasticity, including C-fiber sprouting and propriospinal fiber proliferation exaggerates noxious afferent transmission to the SPNs, causing them to release massive sympathetic discharges that result in severe hypertensive episodes. In parallel, upregulated peripheral vascular sensitivity following SCI exacerbates the hypertensive response by augmenting gastric and pelvic vasoconstriction. Currently, the majority of clinically employed treatments for AD involve anti-hypertensive medications and Botox injections to the bladder. Although these approaches mitigate the severity of AD, they only yield transient effects and target the effector organs, rather than addressing the primary issue of central sympathetic dysregulation. As such, strategies that aim to restore supraspinal reinnervation of SPNs to improve cardiovascular sympathetic regulation are likely more effective for AD. Recent pre-clinical investigations show that cell transplantation therapy is efficacious in reestablishing spinal sympathetic connections and improving hemodynamic per- formance, which holds promise as a potential therapeutic approach.展开更多
Background: selective activation and the contempo- rary recording of A delta and C fibers from Yap laser on the scalp is a new neurophysiological assessment, allowing the selective activation of the nociceptive system...Background: selective activation and the contempo- rary recording of A delta and C fibers from Yap laser on the scalp is a new neurophysiological assessment, allowing the selective activation of the nociceptive system. Objectives: to evaluate if the damage of the nociceptive system was related to post herptic nevral-gia (PHN) development in a sample of 26 patients affected by Herpes zooster (HZ);secondly to assess if the impairment of thermal pathway and PHN development were related. Methods: Thirty-two patients were selected for the study, 26 of these were included in the study, whereas 6 were excluded because of cog- nitive impairment. All 26 study patients were sub- mitted to LEP analysis at baseline (T0) and after six months (T1), and the correlation between clinical thermal disease and the development of PHN was monitored. Results: pain duration was evidenced by the presence or absence of an instrumental signal in patients with acute HZ infection. There was total concordance between the absence of LEP signal and pain duration. The concordance between the clinical thermal disease and the pain duration was statisti- cally significant for 43% of the sample. Conclusions: our results suggested a possible role of LEP for PHN prognosis estimation;indeed, most patients affected by acute HZ, with absence of instrumental LEP signal had pain > 6 months. We also noted a significant (43% of cases) clinical concordance between the thermal pathway damage, the absence of instrumental signal and PHN development. Further studies are needed to address this issue.展开更多
AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism.METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and c...AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism.METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastro-vagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed.RESULTS: Acupuncture-stimulation by exciting Aδ and/or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore- and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which was opposite to the effect when vagotomy was performed. The similar depressive effects were produced by the stimulation at the acupoints homo-segmental to the gastric innervation in the animals with or without spinalization. However, the facilitation induced by the stimulation at the acupoints hetero-segmental to the gastric innervation was not observed in the spinalized animals.CONCLUSION: Facilitative effects of stimulating hetero-segmental acupoints are involved in the intact preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homo-segmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of Aδ and/or C afferent fibers can markedly modulate gastrointestinal motility.展开更多
The author hypothesizes that sleep loss associated with a decrease in serotonergic activity plays a significant role in attempted suicide. Recent research has emphasized the role of the economic recession on the occur...The author hypothesizes that sleep loss associated with a decrease in serotonergic activity plays a significant role in attempted suicide. Recent research has emphasized the role of the economic recession on the occurrence of suicide, but with no attention paid to possible biological aspects. In this brief review, the association between sleep, the serotonergic system, and suicide is initially introduced. Then, with consideration of recent research, a hypothesis regarding the oc- currence of suicide is proposed. Finally, based on that hypothesis, three factors possibly germane to reducing suicides (sufficient sleep duration, activation of the serotonergic system, and activation of the prefrontal cortex) are discussed.展开更多
Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture （EA）- induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analge...Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture （EA）- induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analgesia remain unclear. This study investigates the roles of acid-sensing ion channel 3 （ASIC3） and transient receptor potential vanifioid 1 （TRPV1） receptors in EA-induced segmental and systemic analgesia. Effects of EA at acupoint ST36 with different intensities on the C-fiber reflex and mechanical and thermal pain thresholds were measured among the ASIC3-/-, TRPV1-/-, and C57BL/6 mice. Compared with C57BL/6 mice, the ipsilateral inhibition of EA with 0.8 C-fiber threshold （0.8Tc） intensity on C-fiber reflex was markedly reduced in ASIC3-/- mice, whereas the bilateral inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1-/- mice. The segmental increase in pain thresholds induced by 0.3 mA EA was significantly reduced in ASIC3-/- mice, whereas the systemic enhancement of 1.0 mA EA was markedly decreased in TRPV1-/- mice. Thus, segmental analgesia of EA with lower intensity is partially mediated by ASIC3 receptor on Aβ-fiber, whereas systemic analgesia induced by EA with higher intensity is more likely induced by TRPV1 receptor on Aδ- and C-fibers.展开更多
Action potentials can be induced by external electronic impulsive stimulations applied at one end of the unmyelinated fibers(C-fibers), while some action potentials fail to conduct to the other end of the fiber when t...Action potentials can be induced by external electronic impulsive stimulations applied at one end of the unmyelinated fibers(C-fibers), while some action potentials fail to conduct to the other end of the fiber when the stimulation frequency becomes high. Such a phenomenon is called as conduction failure, which was observed in the biological experiments and related to the painful diabetic neuropathy, inflammation, and trauma in the previous studies. On-off firing pattern was recorded from the fiber when conduction failure happened. In the present study, the diffusion Hodgkin-Huxley(HH) model with resting state near a Hopf bifurcation is adopted to simulate the experimental observations. When the periodic electrical pulses with high frequency are applied to one end of the fiber described by the deterministic HH model, conduction failure and the corresponding firing patterns different from the on-off firing pattern are simulated. When noise is introduced to form the stochastic HH model, the firing pattern corresponding to conduction failure becomes the on-off firing pattern, which is characterised by transition behaviors between on-phase(continuous action potentials) and off-phase(a long quiescent state) and large variations in the durations of both phases. Furthermore, the increase of potassium conductance can enhance the conduction failure degree, which closely matches those observed in the experiment and is suggested to be related to the reduction of pain signals. The results show that noise is an important factor to evoke the on-off firing pattern, reveal the functional capability in the pain signals propagation along C-fiber,and present a possible measure for the treatment of chronic pain.展开更多
基金supported in part by the National Natural Science Foundation of China,No.81100939 and 81773713(to WH),No.81501610(to XC)the Research Project funded by Jiangsu Provincial Government of China,No.BRA2018223(to DGM)+2 种基金the Public Health Center at Jiangnan University of China,No.JUPH201808(to XSW)the Wuxi Commission of Public Health and Family Planning of China,No.MS201717(to XSW)the Project of Academic Development Program by Governments of Jiangsu Province and Nantong City of China(to DGM)
文摘Quantitative assessment of the recovery of nerve function, especially sensory and autonomic nerve function, remains a challenge in the field of nerve regeneration research. We previously found that neural control of vasomotor activity could be potentially harnessed to evaluate nerve function. In the present study, five different models of left sciatic nerve injury in rats were established: nerve crush injury, nerve transection/ suturing, nerve defect/autografting, nerve defect/conduit repair, and nerve defect/non-regeneration. Laser Doppler perfusion imaging was used to analyze blood perfusion of the hind feet. The toe pinch test and walking track analysis were used to assess sensory and motor functions of the rat hind limb, respectively. Transmission electron microscopy was used to observe the density of unmyelinated axons in the injured sciatic nerve. Our results showed that axonotmesis-evoked vasodilatation in the foot 6 months after nerve injury/repair recovered to normal levels in the nerve crush injury group and partially in the other three repair groups;whereas the nerve defect/non-regeneration group exhibited no recovery in vasodilatation. Furthermore, the recovery index of axonotmesis-evoked vasodilatation was positively correlated with toe pinch reflex scores and the density of unmyelinated nerve fibers in the regenerated nerve. As C-fiber afferents are predominantly responsible for dilatation of the superficial vasculature in the glabrous skin in rats, the present findings indicate that axonotmesis-evoked vasodilatation can be used as a novel way to assess C-afferent function recovery after peripheral nerve injury. This study was approved by the Ethics Committee for Laboratory Animals of Nantong University of China (approval No. 20130410-006) on April 10, 2013.
基金supported by NIH NINDS R01NS099076,Morton Cure Paralysis Funds(MCPF)
文摘Autonomic dysreflexia （AD） is a serious cardiovascular disorder in patients with spinal cord injury （SCI）. The primary underlying cause of AD is loss of supraspinal control over sympathetic preganglionic neurons （SPNs） caudal to the injury, which renders the SPNs hyper-responsive to stimulation. Central maladaptive plasticity, including C-fiber sprouting and propriospinal fiber proliferation exaggerates noxious afferent transmission to the SPNs, causing them to release massive sympathetic discharges that result in severe hypertensive episodes. In parallel, upregulated peripheral vascular sensitivity following SCI exacerbates the hypertensive response by augmenting gastric and pelvic vasoconstriction. Currently, the majority of clinically employed treatments for AD involve anti-hypertensive medications and Botox injections to the bladder. Although these approaches mitigate the severity of AD, they only yield transient effects and target the effector organs, rather than addressing the primary issue of central sympathetic dysregulation. As such, strategies that aim to restore supraspinal reinnervation of SPNs to improve cardiovascular sympathetic regulation are likely more effective for AD. Recent pre-clinical investigations show that cell transplantation therapy is efficacious in reestablishing spinal sympathetic connections and improving hemodynamic per- formance, which holds promise as a potential therapeutic approach.
文摘Background: selective activation and the contempo- rary recording of A delta and C fibers from Yap laser on the scalp is a new neurophysiological assessment, allowing the selective activation of the nociceptive system. Objectives: to evaluate if the damage of the nociceptive system was related to post herptic nevral-gia (PHN) development in a sample of 26 patients affected by Herpes zooster (HZ);secondly to assess if the impairment of thermal pathway and PHN development were related. Methods: Thirty-two patients were selected for the study, 26 of these were included in the study, whereas 6 were excluded because of cog- nitive impairment. All 26 study patients were sub- mitted to LEP analysis at baseline (T0) and after six months (T1), and the correlation between clinical thermal disease and the development of PHN was monitored. Results: pain duration was evidenced by the presence or absence of an instrumental signal in patients with acute HZ infection. There was total concordance between the absence of LEP signal and pain duration. The concordance between the clinical thermal disease and the pain duration was statisti- cally significant for 43% of the sample. Conclusions: our results suggested a possible role of LEP for PHN prognosis estimation;indeed, most patients affected by acute HZ, with absence of instrumental LEP signal had pain > 6 months. We also noted a significant (43% of cases) clinical concordance between the thermal pathway damage, the absence of instrumental signal and PHN development. Further studies are needed to address this issue.
基金Supported by National Natural Science Foundation of China, No. C30100245 National Basic Research 973 Program, No. 2005CB523308
文摘AIM: To investigate the acupuncture-modulated gastric motility and its underlying neural mechanism.METHODS: Intragastric pressure and/or waves of gastric contraction in rats were recorded by intrapyloric balloon and changes of gastric motility induced by acupuncture stimulation were compared with the background activity before any stimulation. Gastro-vagal or splanchnic-sympathetic nerves were recorded or cut respectively for investigating the involvement of autonomic nerve pathways. Spinalization experiment was also performed.RESULTS: Acupuncture-stimulation by exciting Aδ and/or C afferent fibers, could only modulate gastric motility. Acupuncture-stimulation on fore- and hind-limbs evoked a moderate gastric motility followed by increased vagus discharges with unchanged sympathetic activity, while the same stimulus to the acupoints in abdomen resulted in reversed effects on gastric motility and autonomic nervous activities. The inhibitory gastric response was completely abolished by splanchnic denervation, but the facilitative gastric response to stimulation of acupoints in limbs was not influenced, which was opposite to the effect when vagotomy was performed. The similar depressive effects were produced by the stimulation at the acupoints homo-segmental to the gastric innervation in the animals with or without spinalization. However, the facilitation induced by the stimulation at the acupoints hetero-segmental to the gastric innervation was not observed in the spinalized animals.CONCLUSION: Facilitative effects of stimulating hetero-segmental acupoints are involved in the intact preparation of vagal nerves and spinal cord, while the inhibitory response induced by stimulating homo-segmental acupoints is involved in the intact preparation of sympathetic nerves. Only the acupuncture-stimulation with intensity over the threshold of Aδ and/or C afferent fibers can markedly modulate gastrointestinal motility.
文摘The author hypothesizes that sleep loss associated with a decrease in serotonergic activity plays a significant role in attempted suicide. Recent research has emphasized the role of the economic recession on the occurrence of suicide, but with no attention paid to possible biological aspects. In this brief review, the association between sleep, the serotonergic system, and suicide is initially introduced. Then, with consideration of recent research, a hypothesis regarding the oc- currence of suicide is proposed. Finally, based on that hypothesis, three factors possibly germane to reducing suicides (sufficient sleep duration, activation of the serotonergic system, and activation of the prefrontal cortex) are discussed.
基金This work was supported by National Natural Science Foundation of China （Nos. 81330087 and 81503668） and Beijing Natural Science Foundation （No. 7132148）.
文摘Previous studies have demonstrated the effects of different afferent fibers on electroacupuncture （EA）- induced analgesia. However, contributions of functional receptors expressed on afferent fibers to the EA analgesia remain unclear. This study investigates the roles of acid-sensing ion channel 3 （ASIC3） and transient receptor potential vanifioid 1 （TRPV1） receptors in EA-induced segmental and systemic analgesia. Effects of EA at acupoint ST36 with different intensities on the C-fiber reflex and mechanical and thermal pain thresholds were measured among the ASIC3-/-, TRPV1-/-, and C57BL/6 mice. Compared with C57BL/6 mice, the ipsilateral inhibition of EA with 0.8 C-fiber threshold （0.8Tc） intensity on C-fiber reflex was markedly reduced in ASIC3-/- mice, whereas the bilateral inhibition of 1.0 and 2.0Tc EA was significantly decreased in TRPV1-/- mice. The segmental increase in pain thresholds induced by 0.3 mA EA was significantly reduced in ASIC3-/- mice, whereas the systemic enhancement of 1.0 mA EA was markedly decreased in TRPV1-/- mice. Thus, segmental analgesia of EA with lower intensity is partially mediated by ASIC3 receptor on Aβ-fiber, whereas systemic analgesia induced by EA with higher intensity is more likely induced by TRPV1 receptor on Aδ- and C-fibers.
基金supported by the National Natural Science Foundation of China(Grant Nos.11872276,11572225)
文摘Action potentials can be induced by external electronic impulsive stimulations applied at one end of the unmyelinated fibers(C-fibers), while some action potentials fail to conduct to the other end of the fiber when the stimulation frequency becomes high. Such a phenomenon is called as conduction failure, which was observed in the biological experiments and related to the painful diabetic neuropathy, inflammation, and trauma in the previous studies. On-off firing pattern was recorded from the fiber when conduction failure happened. In the present study, the diffusion Hodgkin-Huxley(HH) model with resting state near a Hopf bifurcation is adopted to simulate the experimental observations. When the periodic electrical pulses with high frequency are applied to one end of the fiber described by the deterministic HH model, conduction failure and the corresponding firing patterns different from the on-off firing pattern are simulated. When noise is introduced to form the stochastic HH model, the firing pattern corresponding to conduction failure becomes the on-off firing pattern, which is characterised by transition behaviors between on-phase(continuous action potentials) and off-phase(a long quiescent state) and large variations in the durations of both phases. Furthermore, the increase of potassium conductance can enhance the conduction failure degree, which closely matches those observed in the experiment and is suggested to be related to the reduction of pain signals. The results show that noise is an important factor to evoke the on-off firing pattern, reveal the functional capability in the pain signals propagation along C-fiber,and present a possible measure for the treatment of chronic pain.
