scholarly journals Presynaptic NMDA receptors control nociceptive transmission at the spinal cord level in neuropathic pain

2019 ◽  
Vol 76 (10) ◽  
pp. 1889-1899 ◽  
Author(s):  
Meichun Deng ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Nmda Receptors ◽  
Nociceptive Transmission ◽  
Spinal Cord Level ◽  
Presynaptic Nmda Receptors

Calcineurin Regulates Synaptic Plasticity and Nociceptive Transmissionat the Spinal Cord Level

2021 ◽  
pp. 107385842110468
Author(s):  
Yuying Huang ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Neuropathic Pain ◽  
Protein Phosphatase ◽  
Transient Receptor Potential ◽  
Calcineurin Inhibitors ◽  
Receptor Potential ◽  
Transient Receptor Potential Channels ◽  
Negative Feedback Regulation ◽  
Spinal Cord Level ◽  
Calcineurin Activity

Calcineurin, the predominant Ca2+/calmodulin-dependent serine/threonine protein phosphatase (also known as protein phosphatase 2B), is highly expressed in immune T cells and the nervous system, including the dorsal root ganglion and spinal cord. It controls synaptic transmission and plasticity by maintaining the appropriate phosphorylation status of many ion channels present at presynaptic and postsynaptic sites. As such, normal calcineurin activity in neurons and synapses is mainly involved in negative feedback regulation in response to increased neuronal activity and intracellular Ca2+ levels. Calcineurin inhibitors (e.g., cyclosporine and tacrolimus) are widely used as immunosuppressants in tissue and organ transplantation recipients and for treating autoimmune diseases but can cause severe pain in some patients. Furthermore, diminished calcineurin activity at the spinal cord level may play a major role in the transition from acute to chronic neuropathic pain after nerve injury. Restoring calcineurin activity at the spinal cord level produces long-lasting pain relief in animal models of neuropathic pain. In this article, we provide an overview of recent studies on the critical roles of calcineurin in regulating glutamate NMDA and AMPA receptors, voltage-gated Ca2+ channels, potassium channels, and transient receptor potential channels expressed in the spinal dorsal horn and primary sensory neurons.

scholarly journals Alternation of nociceptive transmission at spinal cord level in SART stress rat.

1991 ◽  
Vol 55 ◽  
pp. 280
Author(s):  
Minoru Kawamura ◽  
Hiroyuki Ohara ◽  
Ryozo Yoneda ◽  
Yasushi Kuraishi ◽  
Masamichi Satoh
Keyword(s):  
Spinal Cord ◽  
Nociceptive Transmission ◽  
Spinal Cord Level

Activation of Spinal N-methyl-D-aspartate Receptors Stimulates a Nitric Oxide/Cyclic Guanosine 3′,5′-monophosphate/Glutamate Release Cascade in Nociceptive Signaling 

1999 ◽  
Vol 91 (5) ◽  
pp. 1415-1415 ◽  
Author(s):  
Tomoyuki Kawamata ◽  
Keiichi Omote
Keyword(s):  
Nitric Oxide ◽  
Spinal Cord ◽  
Nmda Receptors ◽  
Soluble Guanylate Cyclase ◽  
Glutamate Release ◽  
No Synthase ◽  
Nociceptive Transmission ◽  
Glutamate Concentration ◽  
Cgmp Pathway ◽  
Synthase Inhibitor

Background Increasing evidence has suggested the possibility that the activation of N-methyl-D-aspartate (NMDA) receptors modulates spinal nociceptive transmission via a nitric oxide (NO)/cyclic guanosine 3',5'-monophosphate (cGMP) pathway. However, the existence and the role of an NO/cGMP pathway in the modulation of spinal nociceptive transmission has been unclear. The authors hypothesized that the activation of NMDA receptors stimulates an NO/cGMP pathway, and this pathway evokes glutamate release within the spinal cord, modulating spinal nociceptive transmission. Methods The authors have examined the effects of an NO synthase inhibitor and a soluble guanylate cyclase inhibitor on the concentrations of NO metabolites (NO2-/NO3-) and glutamate in the cerebrospinal fluid after intrathecal perfusion of NMDA, concomitantly observing pain-related behavior (scratching, biting, and vocalization) in unanesthetized, free-moving rats using an intrathecal microdialysis method. The contents of cGMP in the dorsal horn were also measured using enzyme immunoassay method. Results Intrathecal perfusion of NMDA produced pain-related behavior and increased glutamate and NO2-/NO3-concentrations in a dose-dependent manner. A competitive NMDA receptor antagonist, D,L-2-amino-5-phosphonovaleric acid, completely blocked the NMDA-induced responses. An NO synthase inhibitor, N(G)-monomethyl-L-arginine acetate, at a dose that completely blocked the increase in NO2-/NO3-, inhibited both the NMDA-induced pain-related behavior and the increase in glutamate concentration. In addition, a soluble guanylate cyclase inhibitor, 1H-[1,2,4]oxadiazole[4,3-a]quinoxaline-1-one, also inhibited significantly NMDA-induced pain-related behavior and the increase in glutamate concentration. NMDA induced an increase in cGMP in the dorsal half of the spinal cord, which was blocked by N(G)-monomethyl-L-arginine acetate. Conclusions The results of this study support the hypothesis that the activation of NMDA receptors modulated pain-related behavior via an NO/cGMP/glutamate release cascade within the spinal cord.

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