Regulation of Glutamate Release From Primary Afferents and Interneurons in the Spinal Cord by Muscarinic Receptor Subtypes

2007 ◽  
Vol 97 (1) ◽  
pp. 102-109 ◽  
Author(s):  
Hong-Mei Zhang ◽  
Shao-Rui Chen ◽  
Hui-Lin Pan
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Acetylcholine Receptors ◽  
Glutamate Release ◽  
Critical Role ◽  
Inhibitory Effect ◽  
Primary Afferents ◽  
Muscarinic Acetylcholine Receptors ◽  
Receptor Subtypes ◽  
Dorsal Horn Neurons

Activation of spinal muscarinic acetylcholine receptors (mAChRs) produces analgesia and inhibits dorsal horn neurons through potentiation of GABAergic/glycinergic tone and inhibition of glutamatergic input. To investigate the mAChR subtypes involved in the inhibitory effect of mAChR agonists on glutamate release, evoked excitatory postsynaptic currents (eEPSCs) were recorded in lamina II neurons using whole cell recordings in rat spinal cord slices. The nonselective mAChR agonist oxotremorine-M concentration-dependently inhibited the monosynaptic and polysynaptic EPSCs elicited by dorsal root stimulation. Interestingly, oxotromorine-M caused a greater inhibition of polysynaptic EPSCs (64.7%) than that of monosynaptic EPSCs (27.9%). In rats pretreated with intrathecal pertussis toxin, oxotremorine-M failed to decrease monosynaptic EPSCs but still partially inhibited the polysynaptic EPSCs in some neurons. This remaining effect was blocked by a relatively selective M3 antagonist 4-DAMP. Himbacine, an M2/M4 antagonist, or AFDX-116, a selective M2 antagonist, completely blocked the inhibitory effect of oxotremorine-M on monosynaptic EPSCs. However, the specific M4 antagonist MT-3 did not alter the effect of oxotremorine-M on monosynaptic EPSCs. Himbacine also partially attenuated the effect of oxotremorine-M on polysynaptic EPSCs in some cells and this effect was abolished by 4-DAMP. Furthermore, oxotremorine-M significantly decreased spontaneous EPSCs in seven of 22 (31.8%) neurons, an effect that was blocked by 4-DAMP. This study provides new information that the M2 mAChRs play a critical role in the control of glutamatergic input from primary afferents to dorsal horn neurons. The M3 and M2/M4 subtypes on a subpopulation of interneurons are important for regulation of glutamate release from interneurons in the spinal dorsal horn.

Uterine Cervical Distension Induces cFos Expression in Deep Dorsal Horn Neurons of the Rat Spinal Cord

2003 ◽  
Vol 99 (1) ◽  
pp. 205-211 ◽  
Author(s):  
Chuanyao Tong ◽  
Weiya Ma ◽  
Sang-Wook Shin ◽  
Robert L. James ◽  
James C. Eisenach
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Inhibitory Effect ◽  
Central Canal ◽  
Labor Pain ◽  
Female Rats ◽  
Dorsal Horn Neurons ◽  
Dependent Inhibition ◽  
Dose Dependent Inhibition ◽  
Surgical Preparation

Background Uterine cervical distension underlies labor pain, yet its neurophysiology and pharmacology of inhibition remain unexplored. The authors examined uterine cervical distension-evoked cFos immunoreactivity in rat spinal cords, and the inhibitory effect of spinal cyclo-oxygenase inhibition on cFos expression. Methods Female rats were anesthetized with halothane, and pairs of metal rods were inserted in each cervical os through a mid-line laparotomy. A submaximal distension force (75 g) was applied for either 30 or 60 min, or, in control animals, no force was applied. Other animals received cervical lidocaine infiltration prior to uterine cervical distension. At the end of the experiments, the spinal cord at T12 to L2 levels was harvested and immunostained for cFos protein. Other animals received intrathecal ketorolac (0, 5, 25, and 50 microg; n = 5-6 for each group) prior to uterine cervical distension. Results Uterine cervical distension significantly increased cFos immunoreactivity in the spinal cord from T12 to L2, with most cFos expression in the deep dorsal and central canal regions. Surgical preparation alone without uterine cervical distension resulted in minimal cFos expression, primarily in the superficial dorsal horn. Uterine cervical distension-evoked cFos expression was prevented by prior infiltration of lidocaine into the cervix. Intrathecal ketorolac produced a dose-dependent inhibition of uterine cervical distension-induced cFos expression. Conclusion The present study demonstrates that uterine cervical distension results in a similar pattern of spinal cord neuronal activation as seen with other noxious visceral stimuli. The inhibition of cFos expression by intrathecal ketorolac suggests that spinal cyclo-oxygenase plays a role in uterine cervical distension-induced nociception.

Effect of Differential Delivery of Isoflurane to Head and Torso on Lumbar Dorsal Horn Activity 

1998 ◽  
Vol 88 (4) ◽  
pp. 1055-1061 ◽  
Author(s):  
Joseph F. Antognini ◽  
Earl Carstens ◽  
Etsuo Tabo ◽  
Viktor Buzin
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Control Period ◽  
Inhibitory Effect ◽  
Mechanical Stimulus ◽  
Spinal Cord Dorsal Horn ◽  
Jugular Veins ◽  
Isoflurane Concentration ◽  
Dorsal Horn Neurons ◽  
The Brain

Background The spinal cord appears to be the site where anesthetic agents prevent movement in response to noxious stimuli. When isoflurane is differentially delivered to the head and torso (with low torso concentrations), cranial anesthetic requirements increase compared with systemic administration. The aim of the current study was to test the hypothesis that isoflurane action in the brain has descending influences on spinal cord dorsal horn neurons. A secondary aim was to determine the association, if any, of high cranial concentrations of isoflurane (>6%) with dorsal horn activity. Methods Ten goats were anesthetized with isoflurane and the carotid arteries and jugular veins isolated and cannulated for cerebral bypass. A laminectomy was performed for recording from single lumbar dorsal horn neurons with hind limb mechanical receptive fields (one cell per goat). A standard noxious mechanical stimulus was applied to the dew claw or hoof bulb during a control period with end-tidal isoflurane at 1.3% and during bypass with the following head/torso isoflurane concentrations: 1.3%/1.3%, 3.2%/1.3%, 9.4%/1.3%, 1.3%/0.2%, 3.0%/0.2% and 8.8%/0.3%. Results When torso isoflurane concentration was 1.3%, increasing cranial isoflurane concentration to 3% or 9% had no significant effect on the activity of dorsal horn units. When torso isoflurane was 0.2-0.3%, spontaneous activity increased; however, at these torso concentrations, evoked responses were significantly decreased (-60%) only when cranial isoflurane concentration was increased to 9%. Conclusions Isoflurane action in the brain had an inhibitory effect on dorsal horn activity with the combination of supraclinical cranial and low torso concentrations.

scholarly journals Inhibition of Glycine Re-Uptake: A Potential Approach for Treating Pain by Augmenting Glycine-Mediated Spinal Neurotransmission and Blunting Central Nociceptive Signaling

Biomolecules ◽  
2021 ◽  
Vol 11 (6) ◽  
pp. 864
Author(s):  
Christopher L. Cioffi
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Therapeutic Potential ◽  
Opioid Analgesic ◽  
Critical Role ◽  
Analgesic Efficacy ◽  
Standard Of Care ◽  
Current Standard ◽  
Glycine Transporters ◽  
Pathological Pain

Among the myriad of cellular and molecular processes identified as contributing to pathological pain, disinhibition of spinal cord nociceptive signaling to higher cortical centers plays a critical role. Importantly, evidence suggests that impaired glycinergic neurotransmission develops in the dorsal horn of the spinal cord in inflammatory and neuropathic pain models and is a key maladaptive mechanism causing mechanical hyperalgesia and allodynia. Thus, it has been hypothesized that pharmacological agents capable of augmenting glycinergic tone within the dorsal horn may be able to blunt or block aberrant nociceptor signaling to the brain and serve as a novel class of analgesics for various pathological pain states. Indeed, drugs that enhance dysfunctional glycinergic transmission, and in particular inhibitors of the glycine transporters (GlyT1 and GlyT2), are generating widespread interest as a potential class of novel analgesics. The GlyTs are Na+/Cl−-dependent transporters of the solute carrier 6 (SLC6) family and it has been proposed that the inhibition of them presents a possible mechanism by which to increase spinal extracellular glycine concentrations and enhance GlyR-mediated inhibitory neurotransmission in the dorsal horn. Various inhibitors of both GlyT1 and GlyT2 have demonstrated broad analgesic efficacy in several preclinical models of acute and chronic pain, providing promise for the approach to deliver a first-in-class non-opioid analgesic with a mechanism of action differentiated from current standard of care. This review will highlight the therapeutic potential of GlyT inhibitors as a novel class of analgesics, present recent advances reported for the field, and discuss the key challenges associated with the development of a GlyT inhibitor into a safe and effective agent to treat pain.

scholarly journals Neuron-specific spinal cord translatomes reveal a neuropeptide code for mouse dorsal horn excitatory neurons

2021 ◽  
Vol 11 (1) ◽  
Author(s):  
Rebecca Rani Das Gupta ◽  
Louis Scheurer ◽  
Pawel Pelczar ◽  
Hendrik Wildner ◽  
Hanns Ulrich Zeilhofer
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Functional Organization ◽  
Affinity Purification ◽  
Expression Patterns ◽  
Inhibitory Neurons ◽  
Dorsal Horn Neurons ◽  
Expression Of Genes ◽  
Excitatory Neurons ◽  
Genes Encoding

AbstractThe spinal dorsal horn harbors a sophisticated and heterogeneous network of excitatory and inhibitory neurons that process peripheral signals encoding different sensory modalities. Although it has long been recognized that this network is crucial both for the separation and the integration of sensory signals of different modalities, a systematic unbiased approach to the use of specific neuromodulatory systems is still missing. Here, we have used the translating ribosome affinity purification (TRAP) technique to map the translatomes of excitatory glutamatergic (vGluT2+) and inhibitory GABA and/or glycinergic (vGAT+ or Gad67+) neurons of the mouse spinal cord. Our analyses demonstrate that inhibitory and excitatory neurons are not only set apart, as expected, by the expression of genes related to the production, release or re-uptake of their principal neurotransmitters and by genes encoding for transcription factors, but also by a differential engagement of neuromodulator, especially neuropeptide, signaling pathways. Subsequent multiplex in situ hybridization revealed eleven neuropeptide genes that are strongly enriched in excitatory dorsal horn neurons and display largely non-overlapping expression patterns closely adhering to the laminar and presumably also functional organization of the spinal cord grey matter.

Muscle stretch-induced modulation of noxiously activated dorsal horn neurons of feline spinal cord

2004 ◽  
Vol 48 (2) ◽  
pp. 175-184
Author(s):  
M Björklund ◽  
S Radovanovic ◽  
M Ljubisavljevic ◽  
U Windhorst ◽  
H Johansson
Keyword(s):  
Spinal Cord ◽  
Dorsal Horn ◽  
Muscle Stretch ◽  
Dorsal Horn Neurons
Sign in / Sign up

Export Citation Format

Share Document