• The Korean Journal of Physiology and Pharmacology
• /
• v.9 no.3
• /
• pp.143-147
• /
• 2005

Following peripheral nerve injury, excessive nociceptive inputs result in diverse physiological alterations in the spinal cord substantia gelatinosa (SG), lamina II of the dorsal horn. Here, I report the alterations of excitatory or inhibitory transmission in the SG of a rat model for neuropathic pain ('spared nerve injury'). Results from whole-cell recordings of SG neurons show that the number of distinct primary afferent fibers, identified by graded intensity of stimulation, is increased at 2 weeks after spared nerve injury. In addition, short-term depression, recognized by paired-pulse ratio of excitatory postsynaptic currents, is significantly increased, indicating the increase of glutamate release probability at primary afferent terminals. The peripheral nerve injury also increases the amplitude, but not the frequency, of spontaneous inhibitory postsynaptic currents. These data support the hypothesis that peripheral nerve injury modifies spinal pain conduction and modulation systems to develop neuropathic pain.

• Journal of Korean Medical Ki-Gong Academy
• /
• v.22 no.1
• /
• pp.1-27
• /
• 2023

Objective : This paper provides a narrative review of the research literature on the neurophysiological and neurochemical mechanisms of local vibration while studying the treatment principles and mechanisms of Whidam's vibrator Sugi therapy. Methods : Searches related to vibration therapy research were conducted in PUBMED using "Vibration", "Whole Body Vibration", "Localized Vibration", and "Focal Vibration". The Conditions were limited to review and systematic review. Results : Roberto Casale's paper was selected as an inquiry task and reviewed critically and narratively by referring to other papers. The stimulation process of local vibration (LV) was broadly classified into receptor transmission (pain reception phase), ascending sensory pathway to the spinal cord (segmental phase), and action of the cortex and subcortical structures (systemic control phase) according to the pain pathway. In addition, the role of C-tactile mechanoreceptors, changes in neurotransmitters and neurohormones, LV stimulation below perception threshold (lower threshold), pain control and kinesiologic illusions were specially addressed. In addition, the expression and function of Piezo Channels were added to supplement the human pain and tactile sensing mechanism. Conclusions : LV exerts pain control mechanisms through different interactions that can interfere with pain transmission and pain perception. Since LV provides sufficient neurophysiological reasons for clinical application, it is necessary to expand the use of Whidam's vibrator Sugi therapy to a wider range of clinical applications.

• The Korean Journal of Physiology and Pharmacology
• /
• v.22 no.4
• /
• pp.419-425
• /
• 2018

The superficial dorsal horn of the spinal cord plays an important role in pain transmission and opioid activity. Several studies have demonstrated that opioids modulate pain transmission, and the activation of ${\mu}$-opioid receptors (MORs) by opioids contributes to analgesic effects in the spinal cord. However, the effect of the activation of MORs on GABAergic interneurons and the contribution to the analgesic effect are much less clear. In this study, using transgenic mice, which allow the identification of GABAergic interneurons, we investigated how the activation of MORs affects the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive afferent and GABAergic interneurons. We found that a selective ${\mu}$-opioid agonist, [$D-Ala^2$, $NMe-Phe^4$, Gly-ol]-enkephanlin (DAMGO), induced an outward current mediated by $K^+$ channels in GABAergic interneurons. In addition, DAMGO reduced the amplitude of evoked excitatory postsynaptic currents (EPSCs) of GABAergic interneurons which receive monosynaptic inputs from primary nociceptive C fibers. Taken together, we found that DAMGO reduced the excitability of GABAergic interneurons and synaptic transmission between primary nociceptive C fibers and GABAergic interneurons. These results suggest one possibility that suppression of GABAergic interneurons by DMAGO may reduce the inhibition on secondary GABAergic interneurons, which increase the inhibition of the secondary GABAergic interneurons to excitatory neurons in the spinal dorsal horn. In this circumstance, the sum of excitation of the entire spinal network will control the pain transmission.

• The Korean Journal of Pain
• /
• v.11 no.2
• /
• pp.294-298
• /
• 1998

The feature of neuropathic pain may occur in the absence of any apparent stimulus and be exaggerated in either amplitude or duration. Peripheral nerve injury may produce neuropathic pain and opioids have been shown to be relatively unsatisfactory for the treatment of most cases of neuropathic pain. The NMDA receptor system is involved in transmission and modulation of nociceptive information. We treated patients with severe pain, hyperaesthesia and allodynia with epidural injection of NMDA receptor antagonist, ketamine (10 mg) and morphine (0.5 mg) or other opioid. The combinations provided effective pain management in 23 patients with neuropathic pain.

• The Korean Journal of Pain
• /
• v.34 no.2
• /
• pp.176-184
• /
• 2021

Background: Diabetes-related neuropathic pain frequently occurs, and the underpinning mechanism remains elusive. The periaqueductal gray (PAG) exhibits descending inhibitory effects on central pain transmission. The current work aimed to examine whether inflammatory cytokines regulate mechanical allodynia and thermal hyperalgesia induced by diabetes through the phosphoinositide 3-kinase (PI3K)-mammalian target of rapamycin (mTOR) pathway in the PAG. Methods: Streptozotocin (STZ) was administered intraperitoneally to mimic allodynia and hyperalgesia evoked by diabetes in rats. Behavioral assays were carried out for determining mechanical pain and thermal hypersensitivity. Immunoblot and ELISA were performed to examine PAG protein amounts of interleukin-1β (IL-1β), IL-6, and tumor necrosis factor-α (TNF-α), as well as their corresponding receptors in STZ rats, and the expression of PI3K/protein kinase B (Akt)/mTOR signaling effectors. Results: Increased PAG p-PI3K/p-Akt/p-mTOR protein amounts were observed in STZ-induced animals, a PI3K-mTOR pathway inhibition in the PAG attenuated neuropathic pain responses. Moreover, the PAG concentrations of IL-1β, IL-6, and TNF-α and their receptors (namely, IL-1R, IL-6R, and tumor necrosis factor receptor [TNFR] subtype TNFR1, respectively) were increased in the STZ rats. Additionally, inhibiting IL-1R, IL-6R, and TNFR1 ameliorated mechanical allodynia and thermal hyperalgesia in STZ rats, alongside the downregulation of PI3K-mTOR signaling. Conclusions: Overall, the current study suggests that upregulated proinflammatory cytokines and their receptors in the PAG activate PI3K-mTOR signaling, thereby producing a de-inhibition effect on descending pathways in modulating pain transmission, and eventually contributing to neuropathic pain.

• The Korean Journal of Physiology and Pharmacology
• /
• v.27 no.1
• /
• pp.39-48
• /
• 2023

Spinal nerve injury causes mechanical allodynia and structural imbalance of neurotransmission, which were typically associated with calcium overload. Storeoperated calcium entry (SOCE) is considered crucial elements-mediating intracellular calcium homeostasis, ion channel activity, and synaptic plasticity. However, the underlying mechanism of SOCE in mediating neuronal transmitter release and synaptic transmission remains ambiguous in neuropathic pain. Neuropathic rats were operated by spinal nerve ligations. Neurotransmissions were assessed by whole-cell recording in substantia gelatinosa. Immunofluorescence staining of STIM1 with neuronal and glial biomarkers in the spinal dorsal horn. The endoplasmic reticulum stress level was estimated from qRT-PCR. Intrathecal injection of SOCE antagonist SKF96365 dose-dependently alleviated mechanical allodynia in ipsilateral hind paws of neuropathic rats with ED₅₀ of 18 ㎍. Immunofluorescence staining demonstrated that STIM1 was specifically and significantly expressed in neurons but not astrocytes and microglia in the spinal dorsal horn. Bath application of SKF96365 inhibited enhanced miniature excitatory postsynaptic currents in a dosage-dependent manner without affecting miniature inhibitory postsynaptic currents. Mal-adaption of SOCE was commonly related to endoplasmic reticulum (ER) stress in the central nervous system. SKF96365 markedly suppressed ER stress levels by alleviating mRNA expression of C/ EBP homologous protein and heat shock protein 70 in neuropathic rats. Our findings suggested that nerve injury might promote SOCE-mediated calcium levels, resulting in long-term imbalance of spinal synaptic transmission and behavioral sensitization, SKF96365 produces antinociception by alleviating glutamatergic transmission and ER stress. This work demonstrated the involvement of SOCE in neuropathic pain, implying that SOCE might be a potential target for pain management.

• The Korean Journal of Pain
• /
• v.13 no.1
• /
• pp.19-30
• /
• 2000

Background: Partial nerve injury to a peripheral nerve may induce the development of neuropathic pain which is characterized by symptoms such as spontaneous burning pain, allodynia and hyperalgesia. Though underlying mechanism has not fully understood, sensitization of dorsal horn neurons may contribute to generate such symptoms. Nitric oxide acts as an inter- and intracellular messenger in the nervous system and is produced from L-arginine by nitric oxide synthase (NOS). Evidence is accumulating which indicate that nitric oxide may mediate nociceptive information transmission. Recently, it has been reported that NOS inhibitor suppresses neuropathic pain behavior in an neuropathic pain animal model. This study was conducted to determine whether nitric oxide could be involved in the sensitization of dorsal horn neurons in neuropathic animal model. Methods: Neuropathic animal model was made by tightly ligating the left L5 and L6 spinal nerves and we examined the effects of iontophoretically applied NOS inhibitor (L-NAME) on the dorsal horn neuron's responses to mechanical stimuli within the receptive fields. Results: In normal animals, NOS inhibitor (L-NAME) specifically suppressed the responses to the noxious mechanical stimuli. In neuropathic animals, the dorsal horn neuron's responses to mechanical stimuli were enhanced and NOS inhibitor suppressed the dorsal horn neuron's enhanced responses to non-noxious stimuli as well as those to noxious ones. Conclusions: These results suggest that nitric oxide may mediate nociceptive transmission in normal animal and also mediate sensitization of dorsal horn neurons in neuropathic pain state.

• The Korean Journal of Pain
• /
• v.22 no.1
• /
• pp.1-15
• /
• 2009

Neuropathic pain is often refractory to intervention because of the complex etiology and an incomplete understanding of the mechanisms behind this type of pain. Glial cells, specifically microglia and astrocytes, are powerful modulators of pain and new targets of drug development for neuropathic pain. Glial activation could be the driving force behind chronic pain, maintaining the noxious signal transmission even after the original injury has healed. Glia express chemokine, purinergic, toll-like, glutaminergic and other receptors that enable them to respond to neural signals, and they can modulate neuronal synaptic function and neuronal excitability. Nerve injury upregulates multiple receptors in spinal microglia and astrocytes. Microglia influence neuronal communication by producing inflammatory products at the synapse, as do astrocytes because they completely encapsulate synapses and are in close contact with neuronal somas through gap junctions. Glia are the main source of inflammatory mediators in the central nervous system. New therapeutic strategies for neuropathic pain are emerging such as targeting the glial cells, novel pharmacologic approaches and gene therapy. Drugs targeting microglia and astrocytes, cytokine production, and neural structures including dorsal root ganglion are now under study, as is gene therapy. Isoform-specific inhibition will minimize the side effects produced by blocking all glia with a general inhibitor. Enhancing the anti-inflammatory cytokines could prove more beneficial than administering proinflammatory cytokine antagonists that block glial activation systemically. Research on therapeutic gene transfer to the central nervous system is underway, although obstacles prevent immediate clinical application.

• The Korean Journal of Pain
• /
• v.25 no.1
• /
• pp.38-42
• /
• 2012

Chronic pelvic pain is a common problem with variable etiology. The sympathetic nervous system plays an important role in the transmission of visceral pain regardless of its etiology. Sympathetic nerve block is effective and safe for treatment of pelvic visceral pain. One of them, the inferior hypogastric plexus, is not easily assessable to blockade by local anesthetics and neurolytic agents. Inferior hypogastric plexus block is not commonly used in chronic pelvic pain patients due to pre-sacral location. Therefore, inferior hypogastric plexus is not readily blocked using paravertebral or transdiscal approaches. There is only one report of inferior hypogastric plexus block via transsacral approach. This approach has several disadvantages. In this case a favorable outcome was obtained by using coccygeal transverse approach of inferior hypogastric plexus. Thus, we report a patient who was successfully given inferior hypogastric plexus block via coccygeal transverse approach to treat chronic pelvic pain conditions involving the lower pelvic viscera.

• The Journal of Korean Physical Therapy
• /
• v.13 no.1
• /
• pp.205-218
• /
• 2001

Interpretation of pain by the patients and the observers as well as the methods of treatment remain as varied as are the concepts of pain. The physiologic mechanism of pain is undergoing a serious revision. It is nociceptive receptive mechanism and Melzak concept of gate theory of pain transmission and etc. Therefore pain depend on the evaluator's learning, experience, or specialty.