当前位置: X-MOL 学术Pain › 论文详情
Our official English website, www.x-mol.net, welcomes your feedback! (Note: you will need to create a separate account there.)
Widespread hyperexcitability of nociceptor somata outlasts enhanced avoidance behavior after incision injury.
Pain ( IF 5.9 ) Pub Date : 2024-10-22 , DOI: 10.1097/j.pain.0000000000003443
Alexis Bavencoffe,Elia R Lopez,Kayla N Johnson,Jinbin Tian,Falih M Gorgun,Breanna Q Shen,Drue M Domagala,Michael X Zhu,Carmen W Dessauer,Edgar T Walters

Nociceptors with somata in dorsal root ganglia (DRGs) readily switch from an electrically silent state to a hyperactive state of tonic, nonaccommodating, low-frequency, irregular discharge of action potentials (APs). Spontaneous activity (SA) during this state is present in vivo in rats months after spinal cord injury (SCI) and has been causally linked to SCI pain. Intrinsically generated SA and, more generally, ongoing activity (OA) are induced by various neuropathic conditions in rats, mice, and humans and are retained in nociceptor somata after dissociation and culturing, providing a powerful tool for investigating its mechanisms and functions. The present study shows that long-lasting hyperexcitability that can generate OA during modest depolarization in probable nociceptors dissociated from DRGs of male and female rats is induced by plantar incision injury. OA occurred when the soma was artificially depolarized to a level within the normal range of membrane potentials where large, transient depolarizing spontaneous fluctuations (DSFs) can approach AP threshold. This hyperexcitability persisted for at least 3 weeks, whereas behavioral indicators of affective pain-hind paw guarding and increased avoidance of a noxious substrate in an operant conflict test-persisted for 1 week or less. The most consistent electrophysiological alteration associated with OA was enhancement of DSFs. An unexpected discovery after plantar incisions was hyperexcitability in neurons from thoracic DRGs that innervate dermatomes distant from the injured tissue. Potential in vivo functions of widespread, low-frequency nociceptor OA consistent with these and other findings are to contribute to hyperalgesic priming and to drive anxiety-related hypervigilance.

中文翻译:


伤害感受器胞体的广泛过度兴奋性超过了切口损伤后增强的回避行为。



背根神经节 (DRG) 中具有胞体的伤害感受器很容易从电静音状态转变为强直、不调节、低频、动作电位 (AP) 不规则放电的亢奋状态。这种状态下的自发活动 (SA) 在脊髓损伤 (SCI) 后数月存在于大鼠体内,并且与 SCI 疼痛有因果关系。内在产生的 SA 和更普遍的持续活动 (OA) 是由大鼠、小鼠和人类的各种神经性条件诱导的,并在解离和培养后保留在伤害感受器胞体中,为研究其机制和功能提供了强大的工具。本研究表明,足底切口损伤诱导了从雄性和雌性大鼠的 DRG 分离的可能伤害感受器在适度去极化期间产生 OA 的长期过度兴奋。当胞体被人工去极化至正常膜电位范围内的水平时,就会发生 OA,其中较大的瞬时去极化自发波动 (DSF) 可以接近 AP 阈值。这种过度兴奋持续至少 3 周,而情感疼痛的行为指标 - 后爪保护和在操作性冲突测试中增加对有害基质的回避 - 持续 1 周或更短时间。与 OA 相关的最一致的电生理改变是 DSF 的增强。足底切口后的一个意外发现是胸部 DRG 神经元的过度兴奋性,这些神经元支配远离受伤组织的皮节。与这些和其他发现一致的广泛、低频伤害感受器 OA 的潜在体内功能是导致痛觉过敏启动并驱动与焦虑相关的过度警觉。
更新日期:2024-10-22
down
wechat
bug