scholarly journals Electrophysiological and Morphological Features of Rebound Depolarization Characterized Interneurons in Rat Superficial Spinal Dorsal Horn

2021 ◽  
Vol 15 ◽  
Author(s):  
Mengye Zhu ◽  
Yi Yan ◽  
Xuezhong Cao ◽  
Fei Zeng ◽  
Gang Xu ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Morphological Characteristics ◽  
Substantia Gelatinosa ◽  
Morphological Properties ◽  
Specific Cell ◽  
Membrane Hyperpolarization ◽  
Spinal Dorsal ◽  
C Fibers ◽  
Somatosensory Information

Substantia gelatinosa (SG) neurons, which are located in the spinal dorsal horn (lamina II), have been identified as the “central gate” for the transmission and modulation of nociceptive information. Rebound depolarization (RD), a biophysical property mediated by membrane hyperpolarization that is frequently recorded in the central nervous system, contributes to shaping neuronal intrinsic excitability and, in turn, contributes to neuronal output and network function. However, the electrophysiological and morphological properties of SG neurons exhibiting RD remain unclarified. In this study, whole-cell patch-clamp recordings were performed on SG neurons from parasagittal spinal cord slices. RD was detected in 44.44% (84 out of 189) of the SG neurons recorded. We found that RD-expressing neurons had more depolarized resting membrane potentials, more hyperpolarized action potential (AP) thresholds, higher AP amplitudes, shorter AP durations, and higher spike frequencies in response to depolarizing current injection than neurons without RD. Based on their firing patterns and morphological characteristics, we propose that most of the SG neurons with RD mainly displayed tonic firing (69.05%) and corresponded to islet cell morphology (58.82%). Meanwhile, subthreshold currents, including the hyperpolarization-activated cation current (Ih) and T-type calcium current (IT), were identified in SG neurons with RD. Blockage of Ih delayed the onset of the first spike in RD, while abolishment of IT significantly blunted the amplitude of RD. Regarding synaptic inputs, SG neurons with RD showed lower frequencies in both spontaneous and miniature excitatory synaptic currents. Furthermore, RD-expressing neurons received either Aδ- or C-afferent-mediated monosynaptic and polysynaptic inputs. However, RD-lacking neurons received afferents from monosynaptic and polysynaptic Aδ fibers and predominantly polysynaptic C-fibers. These findings demonstrate that SG neurons with RD have a specific cell-type distribution, and may differentially process somatosensory information compared to those without RD.

scholarly journals Analgesic Effect of Acetaminophen: A Review of Known and Novel Mechanisms of Action

2020 ◽  
Vol 11 ◽  
Author(s):  
Nobuko Ohashi ◽  
Tatsuro Kohno
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Transient Receptor Potential ◽  
Receptor Potential ◽  
Transient Receptor Potential Vanilloid ◽  
Nociceptive Transmission ◽  
Spinal Dorsal ◽  
C Fibers ◽  
Trpv1 Receptors ◽  
The Brain

Acetaminophen is one of the most commonly used analgesic agents for treating acute and chronic pain. However, its metabolism is complex, and its analgesic mechanisms have not been completely understood. Previously, it was believed that acetaminophen induces analgesia by inhibiting cyclooxygenase enzymes; however, it has been considered recently that the main analgesic mechanism of acetaminophen is its metabolization to N-acylphenolamine (AM404), which then acts on the transient receptor potential vanilloid 1 (TRPV1) and cannabinoid 1 receptors in the brain. We also recently revealed that the acetaminophen metabolite AM404 directly induces analgesia via TRPV1 receptors on terminals of C-fibers in the spinal dorsal horn. It is known that, similar to the brain, the spinal dorsal horn is critical to pain pathways and modulates nociceptive transmission. Therefore, acetaminophen induces analgesia by acting not only on the brain but also the spinal cord. In addition, acetaminophen is not considered to possess any anti-inflammatory activity because of its weak inhibition of cyclooxygenase (COX). However, we also revealed that AM404 induces analgesia via TRPV1 receptors on the spinal dorsal horn in an inflammatory pain rat model, and these analgesic effects were stronger in the model than in naïve rats. The purpose of this review was to summarize the previous and new issues related to the analgesic mechanisms of acetaminophen. We believe that it will allow clinicians to consider new pain management techniques involving acetaminophen.

In Vivo Patch-Clamp Analysis of IPSCs Evoked in Rat Substantia Gelatinosa Neurons by Cutaneous Mechanical Stimulation

2000 ◽  
Vol 84 (4) ◽  
pp. 2171-2174 ◽  
Author(s):  
Keita Narikawa ◽  
Hidemasa Furue ◽  
Eiichi Kumamoto ◽  
Megumu Yoshimura
Keyword(s):  
Patch Clamp ◽  
Receptor Antagonist ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Substantia Gelatinosa ◽  
Mechanical Stimuli ◽  
Patch Clamp Technique ◽  
Spinal Dorsal ◽  
Postsynaptic Currents

To know a functional role of inhibitory synaptic responses in transmitting noxious and innoxious information from the periphery to the rat spinal dorsal horn, we examined inhibitory postsynaptic currents (IPSCs) elicited in substantia gelatinosa (SG) neurons by mechanical stimuli applied to the skin using the newly developed in vivo patch-clamp technique. In the majority (80%) of SG neurons examined, a brush stimulus applied to the ipsilateral hind limb produced a barrage of IPSCs that persisted during the stimulus, while a pinch stimulus evoked IPSCs only at its beginning and end. The pinch-evoked IPSCs may have been caused by a touch that occurs at the on/off time of the pinch. The evoked IPSCs were blocked by either a glycine-receptor antagonist, strychnine (4 μM), or a GABAA-receptor antagonist, bicuculline (20 μM). All SG neurons examined received inhibitory inputs from a wide area throughout the thigh and lower leg. When IPSCs were examined together with excitatory postsynaptic currents (EPSCs) in the same neurons, a brush evoked a persistent activity of both IPSCs and EPSCs during the stimulus while a pinch evoked such an activity of EPSCs but not IPSCs. It is suggested that innoxious mechanical stimuli activate a GABAergic or glycinergic circuitry in the spinal dorsal horn. This inhibitory transmission may play an important role in the modulation of noxious information in the SG.

Action of neuropeptide Y on nociceptive transmission in substantia gelatinosa of the adult rat spinal dorsal horn

Neuroscience ◽  
2005 ◽  
Vol 134 (2) ◽  
pp. 595-604 ◽  
Author(s):  
A. Miyakawa ◽  
H. Furue ◽  
T. Katafuchi ◽  
N. Jiang ◽  
T. Yasaka ◽  
...  
Keyword(s):  
Neuropeptide Y ◽  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Substantia Gelatinosa ◽  
Nociceptive Transmission ◽  
Adult Rat ◽  
Spinal Dorsal

Effects of naftopidil on inhibitory transmission in substantia gelatinosa neurons of the rat spinal dorsal horn in vitro

2017 ◽  
Vol 380 ◽  
pp. 205-211 ◽  
Author(s):  
Daisuke Uta ◽  
Du-Jie Xie ◽  
Tsuyoshi Hattori ◽  
Ken-ichi Kasahara ◽  
Megumu Yoshimura
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Substantia Gelatinosa ◽  
Inhibitory Transmission ◽  
Spinal Dorsal

Presynaptic inhibition by baclofen of miniature EPSCs and IPSCs in substantia gelatinosa neurons of the adult rat spinal dorsal horn

Pain ◽  
2000 ◽  
Vol 85 (3) ◽  
pp. 385-393 ◽  
Author(s):  
Minako Iyadomi ◽  
Ikuo Iyadomi ◽  
Eiichi Kumamoto ◽  
Katsumaro Tomokuni ◽  
Megumu Yoshimura
Keyword(s):  
Dorsal Horn ◽  
Presynaptic Inhibition ◽  
Spinal Dorsal Horn ◽  
Substantia Gelatinosa ◽  
Adult Rat ◽  
Spinal Dorsal

scholarly journals Neuron Type-Dependent Synaptic Activity in the Spinal Dorsal Horn of Opioid-Induced Hyperalgesia Mouse Model

2021 ◽  
Vol 13 ◽  
Author(s):  
Austin Kearns ◽  
Jazmine Jayasi ◽  
Xin Liu ◽  
Jigong Wang ◽  
Yuqiang Shi ◽  
...  
Keyword(s):  
Dorsal Horn ◽  
Spinal Dorsal Horn ◽  
Pain Sensitivity ◽  
Specific Cell ◽  
Dependent Manner ◽  
Neuronal Circuit ◽  
Morphine Treatment ◽  
Tonic Firing ◽  
Spinal Dorsal ◽  
Opioid Induced Hyperalgesia

Opioids are widely used for pain relief; however, chronic opioid use causes a paradoxical state of enhanced pain sensitivity, termed “Opioid-induced hyperalgesia (OIH).” Despite the clinical importance of OIH, the detailed mechanism by which it enhances pain sensitivity remains unclear. In this study, we tested whether repeated morphine induces a neuronal circuit polarization in the mouse spinal dorsal horn (SDH). Transgenic mice expressing GFP to neurokinin 1 receptor-expressing neurons (sNK1Rn) and GABAergic interneurons (sGABAn) that received morphine [20 mg/kg, once daily for four consecutive days (i.p.)] developed mechanical hypersensitivity. Repeated morphine altered synaptic strengths in the SDH as a specific cell-type but not in a gender-dependent manner. In sNK1Rn and non-tonic firing neurons, repeated morphine treatment significantly increased frequency of spontaneous excitatory postsynaptic current (sEPSC) and evoked EPSC (eEPSC). In addition, repeated morphine treatment significantly decreased evoked inhibitory postsynaptic current (eIPSC) in sNK1Rn. Conversely, in sGABAn and tonic firing neurons, repeated morphine treatment significantly decreased sEPSC frequency and eEPSC, but had no change of eIPSC in sGABAn. Interestingly, repeated morphine treatment significantly decreased neuronal rheobase of sNK1Rn but had no effect on sGABAn. These findings suggest that spinal neuronal circuit polarization maybe the mechanism of OIH and identify a potential therapeutic mechanism to prevent or treat opioid-induced pain.

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