兴趣范围

beplay苹果手机能用吗研究兴趣

伤害感受器记忆和慢性疼痛

Research Information

伤害感受器记忆和慢性疼痛

Nocteptor SA Sci疼痛模型

Nocteptor SA Sci疼痛模型

伤害感受器是检测损伤和炎症的主要感觉神经元。重复或严重受伤，炎症会导致慢性，甚至终身疼痛。几种形式的慢性疼痛的主要驱动力是伤害感受器的持续过度刺激性和自发性电活动。这些持久的改变代表了身体损伤的细胞记忆，该记忆可能涉及大脑中也用于存储更多传统记忆的机制。我们的目标是定义导致伤害感受器持续过度过度过度的机制，以评估这种过度兴奋性的功能后果，并在伤害感受器中找到新的分子靶标，从而为治疗慢性疼痛提供希望。这些目标是通过两种补充方法来追求的。

Nociceptor mechanisms driving chronic pain after spinal cord injury.脊髓损伤（SCI）引起的永久性疼痛是已知的最棘手的慢性疼痛形式之一。我们发现，SCI几个月后测试的大鼠的行为超敏反应与伤害感受器细胞体的自发活性（SA）的显着，广泛增加，而这种SA既表现为in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in in acTy and in Vivo and to t。分离和培养伤害感受器的第二天。当前的项目采用多学科方法（行为测试，全细胞斑块夹，免疫细胞化学，生物化学，分子生物学）来定义SCI诱导的SA的电生理机制，慢性SA的开发和维持以及Noceptor SA的行为后果的开发和维持的细胞信号改变。

Comparative insights into nociceptor memory functions and mechanisms.Our work and others’ have revealed striking similarities in how the nociceptors of invertebrates and vertebrates detect and “remember” injury-related stimulation. Mollusks offer well-known advantages for relating the properties of identifiable cells to behavioral functions. We use the large marine snail, Aplysia, to define cellular signaling pathways important for the induction and long-term maintenance of hyperexcitability in the cell body, axon, and peripheral and central terminals of identified nociceptors. Some of these signals also contribute to long-term alterations in vertebrate nociceptors, including the cAMP-PKA-CREB and NO-cGMP-PKG pathways. Others have not yet been investigated in vertebrates, such as a potent pathway that depends upon local depolarization (and protein synthesis) but not calcium signals. We found recently that another mollusc, the longfin Atlantic squid, displays long-term nociceptive sensitization of defensive behavior paralleled by sensitization of the peripheral branches of nociceptors. Comparisons of behavioral alterations and nociceptor memory in squid, Aplysia, and rats point to shared functions that have shaped the evolution of nociceptor plasticity and to conserved mechanisms that may be fundamental to many memory-like phenomena, including some forms of chronic pain.

出版物

出版信息

References

  • Crook RJ，Dickson K，Hanlon RT，Walters等。（2014）。伤害性敏化降低了捕食风险。Curr Biol。，24：1121–1125。
  • 克鲁克RJ，Walters等。（2014）。神经义学：自我识别有助于章鱼避免纠缠。Curr Biol。，24：R520–1。
  • Luo J,Walters et，Carlton SM和Hu H.（2013）。靶向疼痛引起的瞬态受体电位通道，以治疗疼痛。Curr Neuropharm。，11（6）：652 - 663。
  • Wu ZZ，Yang Q，Crook RJ，O’Neil RG，Walters等。（2013）。TRPV1 channels make major contributions to behavioral hypersensitivity and spontaneous activity in nociceptors after spinal cord injury.J疼痛。, Oct; 154 (10): 2130-41.
  • Yang Q, Wu ZZ, Crook RJ, Du J, Carlton SM,Walters等。（2013）。KCNQ/KV7通道的开放阻碍了小型DRG神经元中的自发活性和脊髓损伤后慢性疼痛的迹象。J疼痛。，14，S54。
  • Yin s*，Luo J*，Qian A，Du J，Yang Q，Zhou S，Yu W，Du G，Clark RB，Walters等, Carlton SM, Hu H. (2013). Retinoids activate the irritant receptor TRPV1 and produce sensory hypersensitivity.J Clin Invest123（9）：3941-51。
  • Bedi SS，Lago MT，Masha Li，Crook RJ，Grill，RJ，Walters等。（2012）。Spinal cord injury triggers an intrinsic growth-promoting state in nociceptors.J Neurotrauma，29：925–935。
  • Walters等。（2012）。伤害感受器是脊髓损伤后的慢性疼痛驱动因素和超反射症：一种适应性 - 抗腹膜过度功能性的假设。前生理学，3：309（开放式第309条，第13页）。
  • Crook RJ，Lewis T，Hanlon RT，Walters等。（2011）。Peripheral injury induces long-term sensitization of defensive responses to visual and tactile stimuli in the squid Loligo pealeii, Lesueur 1821.J Exp Biol, 214:3173–3185.
  • 克鲁克RJ，Walters等。（2011）。Molluscs的伤害性行为和生理学：动物福利的影响。我的j，52：185–195。
  • Jin M，Wu Z，Chen L，James J，Collins D，Walters等, and O’Neil RG. (2011). Determinants of TRPV4 activity following selective activation by small molecule agonist GSK1016790A.PLOS ONE, 6(2):e16713.
  • Bedi S, Yang Q, Crook R, Du J, Wu Z, Fishman H, Grill R, Carlton S andWalters等。(2010)。Chronic spontaneous activity generated in the somata of small dorsal root ganglion neurons is associated with pain-related behavior following spinal cord injury.J Neurosci30,14870-82。
  • Kunjilwar KK，Fishman HM，Englot DJ，O’Neil RG和Walters等。(2010)。持久的兴奋过度诱导by depolarization in the absence of detectable Ca2+ signals.J Neurophysiol101, 1351-1360.
  • 雷耶斯FD和Walters等。(2010)。在消除可检测到的Ca2+信号的条件下，由去极化引起的持久突触增强。J Neurophysiol103,1283-1294.
  • Toy EC, Weisbrodt N, Dubinsky WP, O’Neil RG,Walters等，危害KP。病例文件：生理，第二版。Lange Medical Books/McGraw-Hill，纽约，（2009年）。
  • Walters等，莫罗兹LL。（2009）。软体动物的伤害记忆：对慢性疼痛和神经系统疾病的进化见解。大脑行为效果，74,206-218。
  • Walters等。（2009）。慢性疼痛，记忆力和伤害：蜗牛和大鼠伤害感受器的进化线索。Int J Comp Psychol，22,127–140。
  • Kunjilwar KK，Fishman HM，Englot DJ，O’Neil RG，Walters等。（2009）。在没有可检测到的Ca2+信号的情况下，由去极化引起的持久过度刺激性，J Neurophysiol，101,1351–1360。
  • Weragoda RMS，Walters等。(2007). Serotonin induces memory-like, rapamycin-sensitive hyperexcitability in sensory axons of Aplysia that contributes to injury responses.J Neurophysiol，98：1231-1239。
  • Song XJ，Wang ZB，Gan Q，Walters等。（2006）。CAPP和CGMP在具有背部根神经节压缩的大鼠中有助于感觉神经元过敏性和超痛性。J Neurophysiol, 95:479-492.
  • Zheng JH，Walters等，歌XJ。（2006）。背根神经神经元的解离可引起过度刺激性，这通过对cAMP和CGMP的反应性提高而保持。J Neurophysiol, 97:15-25.
  • Gasull X, Liao X, Dulin MF, Phelps C,Walters等。(2005). Evidence that long-term hyperexcitability of the sensory neuron soma induced by nerve injury is adaptive.J Neurophysiol3:2218-2230.