Interactions between excitatory amino acids and tachykinins in the rat spinal dorsal horn

Rusin, K.I.; Jiang, Michael; Cerne, R.; Randić, Mirjana

doi:10.1016/0361-9230(93)90261-9

Cited by 61 publications

(28 citation statements)

References 57 publications

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“…The NK1 receptor is coupled to G q/11 and activates PLC leading to formation of IP 3 and diacylglycerol and activation of PKC (Khawaja and Rogers 1996; Krause et al 1993;Mantyh et al 1984). Both PKC and CaMKII are implicated in the facilitatory effects of SP on glutamatergic transmission in the spinal cord (Ikeda et al 2003(Ikeda et al , 2006Rusin et al 1993b). The present results provide strong evidence for a role of PKC in the actions of SP in the RVM as well.…”

Section: Exogenous Sp Facilitates Excitatory Glutamatergic Inputs To mentioning

confidence: 99%

Substance P Enhances Excitatory Synaptic Transmission on Spinally Projecting Neurons in the Rostral Ventromedial Medulla After Inflammatory Injury

Zhang

Hammond²

2009

Journal of Neurophysiology

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Zhang L, Hammond DL. Substance P enhances excitatory synaptic transmission on spinally projecting neurons in the rostral ventromedial medulla after inflammatory injury. J Neurophysiol 102: 1139 -1151, 2009. First published June 3, 2009 doi:10.1152/jn.91337.2008. It has been proposed, but not directly tested, that persistent inflammatory nociception enhances excitatory glutamatergic inputs to neurons in the rostral ventromedial medulla (RVM), altering the activity and function of these neurons. This study used whole cell patch-clamp methods to record evoked excitatory postsynaptic currents (eEPSCs) in spinally projecting RVM neurons from rats injected with saline or complete Freund's adjuvant (CFA) 3-4 days earlier and to examine the role of substance P (SP) in modulating excitatory synaptic transmission. Input-output relationships demonstrated that CFA treatment facilitated fast excitatory glutamatergic inputs to type 1 and type 2 nonserotonergic spinally projecting RVM neurons, but not to type 3 neurons. The facilitation in type 1 and 2 neurons was dependent on neurokinin-1 (NK1) and N-methyl-D-aspartate (NMDA) receptors and prevented by the PKC inhibitor GF109203X. In a subset of neurons from naïve rats, SP mimicked the effects of CFA and increased the potency and efficacy of glutamatergic synaptic transmission. The facilitation was prevented by 10 M GF109203X, but not by 10 M KN93, a CaMKII inhibitor. SP (0.3-3 M) by itself produced concentration-dependent inward currents in most nonserotonergic, but not serotonergic neurons. The present study is the first demonstration, at the cellular level, that persistent inflammatory nociception leads to a sustained facilitation of fast excitatory glutamatergic inputs to RVM neurons by an NK1 and NMDA receptor-dependent mechanism that involves PKC. Further, it demonstrates that the facilitation is restricted to specific populations of RVM neurons that by inference may be pain facilitatory neurons.

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Section: Exogenous Sp Facilitates Excitatory Glutamatergic Inputs To mentioning

confidence: 99%

Substance P Enhances Excitatory Synaptic Transmission on Spinally Projecting Neurons in the Rostral Ventromedial Medulla After Inflammatory Injury

Zhang

Hammond²

2009

Journal of Neurophysiology

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“…Interestingly NK2 receptor, which has high affinity for neurokinin A, but not NK1, which has high affinity for substance P, were found to be involved in the excitatory modulation of inspiratory activity [169]. It is possible that NKA modulates the neuronal response to glutamate in the NTS since NKA has been shown to modulate NMDA and AMPA activation in neurons of the dorsal horn [170]; however this has not properly been tested in the NTS.…”

Section: Respirationmentioning

confidence: 99%

Putative roles of neuropeptides in vagal afferent signaling

Lartigue

2014

Physiology & Behavior

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The vagus nerve is a major pathway by which information is communicated between the brain and peripheral organs. Sensory neurons of the vagus are located in the nodose ganglia. These vagal afferent neurons innervate the heart, the lung and the gastrointestinal tract, and convey information about peripheral signals to the brain important in the control of cardiovascular tone, respiratory tone, and satiation, respectively. Glutamate is thought to be the primary neurotransmitter involved in conveying all of this information to the brain. It remains unclear how a single neurotransmitter can regulate such an extensive list of physiological functions from a wide range of visceral sites. Many neurotransmitters have been identified in vagal afferent neurons and have been suggested to modulate the physiological functions of glutamate. Specifically, the anorectic peptide transmitters, cocaine and amphetamine regulated transcript (CART) and the orexigenic peptide transmitters, melanin concentrating hormone (MCH) are differentially regulated in vagal afferent neurons and have opposing effects on food intake. Using these two peptides as a model, this review will discuss the potential role of peptide transmitters in providing a more precise and refined modulatory control of the broad physiological functions of glutamate, especially in relation to the control of feeding.

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“…Methods used have ranged from studying how candidate agents affect neurotransmitter release in vivo and in vitro to electrophysiological studies monitoring dorsal root ganglion (DRG) responsiveness and postsynaptic neuronal firing. Although glutamate is almost certainly the primary mediator of nociceptive transmission at this first synapse, other neurochemicals, notably the tachykinin peptides SP and neurokinin (NK) A, are major contributors (6,7). These peptides are present in a proportion of the small primary afferent neurons that terminate in the outer laminae of the dorsal horn, lamina I and lamina II (8,9); are released by high intensity stimulation (10)(11)(12)(13)(14)(15)(16); enhance the excitability of spinal neurons to noxious inputs (17)(18)(19); and contribute to a 'window' of noxious stimulus-evoked behaviours (20).…”

Section: Pharmacological Controls Of Primarymentioning

confidence: 99%

Presynaptic control of nociceptor signalling: Differential influence of Mu Opioid and GABAergic Systems

Riley

Trafton

Basbaum

2000

Pain Research and Management

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It is difficult to pick a topic to discuss that adequately honours Ron Melzack's many years of pain research. This is particularly problematic if one is cognizant of the tremendous emphasis that Ron puts on the distinction between pain and nociception. Indeed, the thread that binds so many of Ron's studies is that the complexity of the pain experience will not be understood if one exclusively concentrates on the processing of nociceptive messages at the level of the periphery or spinal cord. Ron always emphasized the importance of affective and cognitive components of the pain experience. These elements of the pain experience, so beautifully and memorably discussed in Melzack and Casey's (1) theoretical review, must always be included when this topic is addressed. Dr Allan Basbaum was a student of Ron's in an undergradu- The relative contribution of pre-and postsynaptic controls to the flow of nociceptive information at the level of the spinal cord has been one of Ron Melzack's longstanding interests and a key issue in the formulation of the gate control theory. The authors review their own studies, in which they monitored internalization of the neurokinin-1 receptor to examine specifically the action of two classically inhibitory systems -mu opioid and gamma-amino butyric acid (GABA) -on noxious stimulus-evoked tachykinin signalling in the rat spinal cord. Evidence that opioids and GABAergic controls operate differently on the central consequences of any noxious stimulus-induced substance P release is provided. Whereas at least 80% of the tachykinin signalling remained intact after even the highest concentration of spinal morphine or D-Ala2, NMe-phe4, Glyol5-enkephalin administration, spinal administration of the GABA B receptor agonist baclofen had a dramatic inhibitory effect. These findings are discussed in light of the disappointing clinical utility of baclofen and neurokinin-1 receptor antagonists to combat pain. Key Words: Gamma-amino butyric acid; Mu opioid; Neurokinin 1 receptors; Receptor internalization; Spinal cord; TachykininsCommande présynaptique de la transmission des signaux par les nocicepteurs : mécanisme d'action des opioïdes de type mu et du GABA Le rôle relatif des commandes pré-et postsynaptiques dans la transmission des signaux nociceptifs dans la moelle épinière, en plus de susciter l'intérêt soutenu de Ron Melzack, a constitué un pilier de la théorie du ‹‹ portillon ››. Les auteurs ont passé en revue leurs propres études dans lesquelles ils se sont penchés sur l'endocytose des récep-teurs de la neurokinine 1 afin d'étudier le mécanisme d'action de deux inhibiteurs classiques, les opioïdes de type mu et l'acide gammaaminobutyrique (GABA), sur la transmission de la tachykinine déclen-chée par un stimulus nocif dans la moelle épinière du rat. Ils ont recueilli des preuves selon lesquelles les opioïdes et le GABA agissent différemment sur les effets centraux de la libération de la substance P, provoquée par un stimulus nocif. Tandis qu'au moins 80 % de la transmission des signaux par la tac...

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Interactions between excitatory amino acids and tachykinins in the rat spinal dorsal horn

Cited by 61 publications

References 57 publications

Substance P Enhances Excitatory Synaptic Transmission on Spinally Projecting Neurons in the Rostral Ventromedial Medulla After Inflammatory Injury

Substance P Enhances Excitatory Synaptic Transmission on Spinally Projecting Neurons in the Rostral Ventromedial Medulla After Inflammatory Injury

Putative roles of neuropeptides in vagal afferent signaling

Presynaptic control of nociceptor signalling: Differential influence of Mu Opioid and GABAergic Systems

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