Synchronized cluster firing, a distinct form of sensory neuron activation, drives spontaneous pain.
Neuron
; 110(2): 209-220.e6, 2022 01 19.
Article
in En
| MEDLINE
| ID: mdl-34752775
ABSTRACT
Spontaneous pain refers to pain occurring without external stimuli. It is a primary complaint in chronic pain conditions and remains difficult to treat. Moreover, the mechanisms underlying spontaneous pain remain poorly understood. Here we employed in vivo imaging of dorsal root ganglion (DRG) neurons and discovered a distinct form of abnormal spontaneous activity following peripheral nerve injury clusters of adjacent DRG neurons firing synchronously and sporadically. The level of cluster firing correlated directly with nerve injury-induced spontaneous pain behaviors. Furthermore, we demonstrated that cluster firing is triggered by activity of sympathetic nerves, which sprout into DRGs after injury, and identified norepinephrine as a key neurotransmitter mediating this unique firing. Chemogenetic and pharmacological manipulations of sympathetic activity and norepinephrine receptors suggest that they are necessary and sufficient for DRG cluster firing and spontaneous pain behavior. Therefore, blocking sympathetically mediated cluster firing may be a new paradigm for treating spontaneous pain.
Key words
Full text:
1
Database:
MEDLINE
Main subject:
Spinal Nerves
/
Ganglia, Spinal
Limits:
Humans
Language:
En
Journal:
Neuron
Journal subject:
NEUROLOGIA
Year:
2022
Type:
Article
Affiliation country:
United States