神经科学
光遗传学
兴奋性突触后电位
伤害
痛觉超敏
突触后电位
有害刺激
SNi公司
生物
儿茶酚胺能
伤害感受器
痛觉过敏
抑制性突触后电位
遗传学
受体
水解
生物化学
儿茶酚胺
酸水解
作者
Charles A. Warwick,Colleen Cassidy,Junichi Hachisuka,Margaret C. Wright,Kyle M. Baumbauer,Peter Adelman,Kuan H. Lee,Kelly M. Smith,Tayler D. Sheahan,Sarah E. Ross,H. Richard Koerber
出处
期刊:Pain
[Ovid Technologies (Wolters Kluwer)]
日期:2021-02-04
卷期号:162 (7): 2120-2131
被引量:28
标识
DOI:10.1097/j.pain.0000000000002227
摘要
Abstract Most cutaneous C fibers, including both peptidergic and nonpeptidergic subtypes, are presumed to be nociceptors and respond to noxious input in a graded manner. However, mechanically sensitive, nonpeptidergic C fibers also respond to mechanical input in the innocuous range, so the degree to which they contribute to nociception remains unclear. To address this gap, we investigated the function of nonpeptidergic afferents using the Mrgprd Cre allele. In real-time place aversion studies, we found that low-frequency optogenetic activation of Mrgrpd Cre lineage neurons was not aversive in naive mice but became aversive after spared nerve injury (SNI). To address the underlying mechanisms of this allodynia, we recorded responses from lamina I spinoparabrachial (SPB) neurons using the semi-intact ex vivo preparation. After SNI, innocuous brushing of the skin gave rise to abnormal activity in lamina I SPB neurons, consisting of an increase in the proportion of recorded neurons that responded with excitatory postsynaptic potentials or action potentials. This increase was likely due, at least in part, to an increase in the proportion of lamina I SPB neurons that received input on optogenetic activation of Mrgprd Cre lineage neurons. Intriguingly, in SPB neurons, there was a significant increase in the excitatory postsynaptic current latency from Mrgprd Cre lineage input after SNI, consistent with the possibility that the greater activation post-SNI could be due to the recruitment of a new polysynaptic circuit. Together, our findings suggest that Mrgprd Cre lineage neurons can provide mechanical input to the dorsal horn that is nonnoxious before injury but becomes noxious afterwards because of the engagement of a previously silent polysynaptic circuit in the dorsal horn.
科研通智能强力驱动
Strongly Powered by AbleSci AI