Nitric oxide as a messenger between neurons and satellite glial cells in dorsal root ganglia

Abstract

Abnormal neuronal activity in sensory ganglia contributes to chronic pain. There is evidence that signals can spread between cells in these ganglia, which may contribute to this activity. Satellite glial cells (SGCs) in sensory ganglia undergo activation following peripheral injury and participate in cellular communication via gap junctions and chemical signaling. Nitric oxide (NO) is released from neurons in dorsal root ganglia (DRG) and induces cyclic GMP (cGMP) production in SCGs, but its role in SGC activation and neuronal excitability has not been explored. It was previously reported that induction of intestinal inflammation with dinitrobenzoate sulfonate (DNBS) increased gap junctional communications among SGCs, which contributed to neuronal excitability and pain. Here we show that DNBS induced SGC activation in mouse DRG, as assayed by glial fibrillary acidic protein upregulation. DNBS also upregulated cGMP level in SGCs, consistent with NO production. In vitro studies on intact ganglia from DNBS‐treated mice showed that blocking NO synthesis inhibited both SGCs activation and cGMP upregulation, indicating an ongoing NO production. Application of NO donor in vitro induced SGC activation, augmented gap junctional communications, and raised neuronal excitability, as assessed by electrical recordings. The cGMP analog 8‐Br‐cGMP mimicked these actions, confirming the role of the NO‐cGMP pathway in intraganglionic communications. NO also augmented Ca2+ waves propagation in DRG cultures. It is proposed that NO synthesis in DRG neurons increases after peripheral inflammation and that NO induces SGC activation, which in turn contributes to neuronal hyperexcitability. Thus, NO plays a major role in neuron–SGC communication.

Emerging importance of satellite glia in nervous system function and dysfunction

“…Active neurons release nitric oxide, which diffuses rapidly over the narrow gap between them and the SGCs. Nitric oxide mimics the observed changes in SGCs that occur after nerve insult 83 , and thus appears to be a key element in SGC activation.…”

How Periodontal Disease and Presence of Nitric Oxide Reducing Oral Bacteria Can Affect Blood Pressure

“…Three NOS isoforms have been studied and they take their names from the tissues they identified: Neuronal NOS (nNOS, NOS 1), inducible NOS (iNOS, NOS 2), and endothelial NOS (eNOS, NOS 3) [ 18 ]. The nNOS was discovered in the brain and is involved in central and peripheral neuronal signal [ 19 ]. The iNOS, the inducible form of NOS, detected in macrophages, produces high levels of NO when such cells are activated.…”

TLR7 Is Expressed by Support Cells, but Not Sensory Neurons, in Ganglia 

“…As in other tissues, macrophages in ganglia are phagocytic cells that contribute to antigenpresentation [36,37], whereas satellite glial cells are unique to peripheral nervous tissues, providing structural support by closely surrounding neuronal somata and directly communicating with other satellite glial cells via gap junctions [35]. Following nerve injury, neuronal mediators including nitric oxide and ATP activate macrophages and satellite glial cells [38,39], and in turn, support cells contribute to nerve regeneration and repair [40,41]. Activated support cells also release in ammatory cytokines TNFalpha and IL-1beta [39], which sensitize neuronal nociceptors and increase nerve excitability to acutely enhance sensations of pain [34,42].…”