Objective: Transient receptor potential vanilloid subfamily type 1 (TRPV1), a most specific marker of the nociceptive primary afferent, is expressed in peptidergic and non-peptidergic primary afferents innervating skin and viscera. However, its expression in sensory fibers to skeletal muscle is not well known. In this study, we studied the neurochemical characteristics of TRPV1-positive primary afferents to skeletal muscles. Methods: Sprague-Dawley rats were injected with total $20{\mu}l$ of 1% fast blue (FB) into the gastrocnemius and erector spinae muscle and animals were perfused 4 days after injection. FB-positive cells were traced in the L4-L5 (for gastrocnemius muscle) and L2-L4 (for erector spinae muscle) dorsal root ganglia. The neurochemical characteristics of the muscle afferents were studied with multiple immunofluorescence with TRPV1, calcitonin gene-related peptide (CGRP) and $P2X_3$. To identify spinal neurons responding to noxious stimulus to the skeletal muscle, 10% acetic acids were injected into the gastrocnemius and erector spinae muscles and expression of phospho extracellular signal-regulated kinase (pERK) in spinal cords were identified with immunohistochemical method. Results: TRPVl was expressed in about 49% of muscle afferents traced from gastrocnemius and 40% of erector spinae. Sixty-five to 60% of TRPV1-positive muscles afferents also expressed CGRP. In contrast, expression of $P2X_3$ immnoreaction in TRPV1-positive muscle afferents were about 20%. TRPV1-positive primary afferents were contacted with spinal neurons expressing pERK after injection of acetic acid into the muscles. Conclusion: It is consequently suggested that nociception from skeletal muscles are mediated by TRPV1-positive primary afferents and majority of them are also peptidergic.
Hwang, Min Sub;Hwang, Ji Hye;Kang, Seok Yong;Kang, An Na;Roh, Hyo Sun;Park, Yong-Ki
The Korea Journal of Herbology
/
v.31
no.6
/
pp.63-71
/
2016
Objective : To suggest a scientific evidence of Aconitum carmichaeli Debx. (Aconiti Lateralis Radix Preparata: ALRP) as one of cooling and heating medicines on the regulation of body temperature, we investigated the effects of ALRP water extract on hypothyroidism. Methods : Hypothyroidism was induced by intradermal injection with PTU for 4 weeks in SD rats. ALRP extract or L-thyroxine as a control drug was orally administrated for 2 weeks with PTU injection in rats. The physiological and serological parameters were measured in rats. The histological change of thyroid tissues was observed by H&E staining, and also the expression of thermo-regulating proteins was determined by Western blot in dorsal root ganglia and brain tissues of rats. Results : The administration of ALRP extract in PTU-induced hypothyroidism rats was significantly increased body temperature, but did not changes on body weight, food and water intake. ALRP extract did not effect on the levels of TSH and T4 in the hypothyroidism rats. ALRP extract significantly decreased the levels of GPT, glucose, HDL-cholesterol, LDL-cholesterol, and total cholesterol in the hypothyroidism rats. In histological observation, the enlarged epithelium and atrophic follicles with higher concentration of follicular cells on hypothyroidism were improved by ALRP extract. In addition, ALRP extract increased the expression of TRPV1 and TRPM8 ion channel proteins in hypothyroidism rats. Conclusion : These results indicate that ALRP extract can improve PTU-induced hypothyroidism through regulation of body temperature and lipid accumulation. The action mechanism of ALRP extract is related with body temperature control by thermoregulation with TRP ion channels.
Naseer, Muhammad Imran;Alwasiyah, Mohammad Khalid;Abdulkareem, Angham Abdulrahman;Bajammal, Rayan Abdullah;Trujillo, Carlos;Abu-Elmagd, Muhammad;Jafri, Mohammad Alam;Chaudhary, Adeel G.;Al-Qahtani, Mohammad H.
Genes and Genomics
/
v.40
no.11
/
pp.1149-1155
/
2018
Epileptic encephalopathies are genetically heterogeneous disorders which leads to epilepsy and cause neurological disorders. Seizure threshold 2 (SZT2) gene located on chromosome 1p34.2 encodes protein mainly expressed predominantly in the parietal and frontal cortex and dorsal root ganglia in the brain. Previous studies in mice showed that mutation in this gene can confers low seizure threshold, enhance epileptogenesis and in human may leads to facial dysmorphism, intellectual disability, seizure and macrocephaly. Objective of this study was to find out novel gene or novel mutation related to the gene phenotype. We have identified a large consanguineous Saudi family segregating developmental delay, intellectual disability, epilepsy, high forehead and macrocephaly. Exome sequencing was performed in affected siblings of the family to study the novel mutation. Whole exome sequencing data analysis, confirmed by subsequent Sanger sequencing validation study. Our results showed a novel homozygous mutation (c.9368G>A) in a substitution of a conserved glycine residue into a glutamic acid in the exon 67 of SZT2 gene. The mutation was ruled out in 100 unrelated healthy controls. The missense variant has not yet been reported as pathogenic in literature or variant databases. In conclusion, the here detected homozygous SZT2 variant might be the causative mutation that further explain epilepsy and developmental delay in this Saudi family.
Doo, A Ram;Choi, Jin-Wook;Lee, Ju-Hyung;Kim, Ye Sull;Ki, Min-Jong;Han, Young Jin;Son, Ji-Seon
The Korean Journal of Pain
/
v.32
no.3
/
pp.215-222
/
2019
Background: Several nerve blocks can reduce the incidence of postherpetic neuralgia (PHN) as well as relieve acute zoster-related pain, but the long-term outcome of PHN has not been clearly determined. This study investigated the efficacy of selective nerve root block (SNRB) for herpes zoster (HZ) on the long-term outcome of PHN. Methods: We prospectively conducted an interview of patients who had undergone an SNRB for HZ from January 2006 to December 2016 to evaluate their long-term PHN status. The relationship between the time from HZ onset to the first SNRB and the long-term outcome of PHN was investigated. Results: The data of 67 patients were collected. The patients were allocated to acute ($SNRB{\leq}14days$, n = 16) or subacute (SNRB > 14 days, n = 51) groups. The proportions of cured patients were 62.5% and 25.5% in the acute and subacute groups (P = 0.007), respectively. In logistic regression, an SNRB >14 days was the significant predictor of PHN (adjusted odd ratio, 3.89; 95% confidence interval, 1.02-14.93; P = 0.047). Kaplan-Meier analysis revealed that time from the SNRB to the cure of PHN was significantly shorter in the acute group ($2.4{\pm}0.7yr$) than in the subacute group ($5.0{\pm}0.4yr$; P = 0.003). Conclusions: An early SNRB during the acute stage of HZ (within 14 days) appears to decrease the incidence and shorten the duration of PHN, with a median of 5.0 years of follow-up.
Yoon, Cindy W;Jeong, Hye Jin;Seo, Seongho;Lee, Sang-Yoon;Suh, Mee Kyung;Heo, Jae-Hyeok;Lee, Yeong-Bae;Park, Kee Hyung;Okamura, Nobuyuki;Lee, Kyoung-Min;Noh, Young
Dementia and Neurocognitive Disorders
/
v.17
no.3
/
pp.110-119
/
2018
Background and Purpose: To analyze $^{18}F-THK5351$ positron emission tomography (PET) scans of patients with clinically diagnosed nonfluent/agrammatic variant primary progressive aphasia (navPPA). Methods: Thirty-one participants, including those with Alzheimer's disease (AD, n=13), navPPA (n=3), and those with normal control (NC, n=15) who completed 3 Tesla magnetic resonance imaging, $^{18}F-THK5351$ PET scans, and detailed neuropsychological tests, were included. Voxel-based and region of interest (ROI)-based analyses were performed to evaluate retention of $^{18}F-THK5351$ in navPPA patients. Results: In ROI-based analysis, patients with navPPA had higher levels of THK retention in the Broca's area, bilateral inferior frontal lobes, bilateral precentral gyri, and bilateral basal ganglia. Patients with navPPA showed higher levels of THK retention in bilateral frontal lobes (mainly left side) compared than NC in voxel-wise analysis. Conclusions: In our study, THK retention in navPPA patients was mainly distributed at the frontal region which was well correlated with functional-radiological distribution of navPPA. Our results suggest that tau PET imaging could be a supportive tool for diagnosis of navPPA in combination with a clinical history.
Objective : Globus pallidus interna (GPi) is acknowledged as an essential treatment for advanced Parkinson's disease (PD). Nonetheless, the neurotransmitter study about its results is undiscovered. The goal of this research was to examine influences of entopeduncular nucleus (EPN) stimulation, identical to human GPi, in no-lesioned (NL) rat and 6-hydroxydopamine (6-HD)-lesioned rat on glutamate change in the striatum. Methods : Extracellular glutamate level changes in striatum of NL category, NL with deep brain stimulation (DBS) category, 6-HD category, and 6-HD with DBS category were examined using microdialysis and high-pressure liquid chromatography. Tyrosine hydroxylase (TH) immunoreactivities in substantia nigra and striatum of the four categories were also analyzed. Results : Extracellular glutamate levels in the striatum of NL with DBS category and 6-HD with DBS category were significantly increased by EPN stimulation compared to those in the NL category and 6-HD category. EPN stimulation had no significant effect on the expression of TH in NL or 6-HD category. Conclusion : Clinical results of GPi DBS are not only limited to direct inhibitory outflow to thalamus. They also include extensive alteration within basal ganglia.
Background: The study investigated virtual reality (VR) immersion in alleviating procedure-related pain in patients with chronic pain undergoing fluoroscopy-guided minimally-invasive intervention in a prone position at an outpatient clinic. Methods: In this prospective randomized controlled study, 38 patients undergoing lumbar sympathetic ganglion block were randomized into either the VR or the control group. In the VR group, procedure-related pain was controlled via infiltration of local anesthetics while watching a 30-minute VR hypnotic program. In the control group, the skin infiltration alone was used, with the VR device switched off. The primary endpoint was an 11-point score on the numerical rating scale, indicating procedure-related pain. Patients' satisfaction with pain control, anxiety levels, the need for additional local anesthetics during the procedure, hemodynamic stability, and any adverse events were assessed. Results: Procedure-related pain was significantly lower in the VR group (3.7 ± 1.4) than in the control group (5.5 ± 1.7; P = 0.002). Post-procedural anxiety was lower in the VR group than in the control group (P = 0.025), with a significant reduction from pre-procedural anxiety (P < 0.001). Although patients' satisfaction did not differ significantly (P = 0.158) between the groups, a higher number of patients required additional local anesthetics in the control group (n = 13) than in the VR group (n = 4; P = 0.001). No severe adverse events occurred in either group during the study. Conclusions: VR immersion can be safely used as a novel adjunct to reduce procedural pain and anxiety during fluoroscopic pain intervention.
Kim, Jae-Yeon;Abdi, Salahadin;Huh, Billy;Kim, Kyung-Hoon
The Korean Journal of Pain
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v.34
no.1
/
pp.4-18
/
2021
Except for carbamazepine for trigeminal neuralgia, gabapentinoid anticonvulsants have been the standard for the treatment of neuropathic pain. Pregabalin, which followed gabapentin, was developed with the benefit of rapid peak blood concentration and better bioavailability. Mirogabalin besylate (DS-5565, Tarlige®) shows greater sustained analgesia due to a high affinity to, and slow dissociation from, the α2δ-1 subunits in the dorsal root ganglion (DRG). Additionally, it produces a lower level of central nervous system-specific adverse drug reactions (ADRs), due to a low affinity to, and rapid dissociation from, the α2δ-2 subunits in the cerebellum. Maximum plasma concentration is achieved in less than 1 hour, compared to 1 hour for pregabalin and 3 hours for gabapentin. The plasma protein binding is relatively low, at less than 25%. As with all gabapentinoids, it is also largely excreted via the kidneys in an unchanged form, and so the administration dose should also be adjusted according to renal function. The equianalgesic daily dose for 30 mg of mirogabalin is 600 mg of pregabalin and over 1,200 mg of gabapentin. The initial adult dose starts at 5 mg, given orally twice a day, and is gradually increased by 5 mg at an interval of at least a week, to 15 mg. In conclusion, mirogabalin is anticipated to be a novel, safe gabapentinoid anticonvulsant with a greater therapeutic effect for neuropathic pain in the DRG and lower ADRs in the cerebellum.
Sencan, Savas;Yolcu, Gunay;Bilim, Serhad;Kenis-Coskun, Ozge;Gunduz, Osman Hakan
The Korean Journal of Pain
/
v.35
no.1
/
pp.106-113
/
2022
Background: Coccygodynia is one of the chronic, refractory painful musculoskeletal disorders. Interventional procedures are applied to patients unresponsive to initial treatment in coccygodynia. This study aims to compare the treatment outcomes of ganglion impar block (GIB) and caudal epidural steroid injection (CESI) in patients with chronic coccygodynia. Methods: This study was a prospective randomized comparison study conducted between June 2019 and January 2021. Patients diagnosed with chronic coccygodynia were randomly divided into two groups: the GIB group and the CESI group. The severity of pain, presence of neuropathic pain, and quality of life were evaluated using the Numeric Rating Scale, Leeds Assessment of the Neuropathic Symptoms and Signs Scale, and Short Form-12 Health Survey (SF-12), respectively. Results: A total of 34 patients in each group were included in the final analyses. While there was a significant decrease in pain intensity in both groups in the 3-month follow-up, this decrease was more significant in the GIB group at the 3rd week. There was a significant improvement in the SF-12 physical score and the number of patients with neuropathic pain in both groups in the 3rd week, but this improvement was not observed in the 3rd month. Conclusions: Although GIB may provide more pain relief in short term, both GIB and CESI are useful treatment methods in coccygodynia unresponsive to more conservative treatments.
Background: Different views have been proposed on the radiofrequency treatment modes and parameters of radiofrequency thermocoagulation of the spinal dorsal root ganglion for the treatment of postherpetic neuralgia (PHN). It is urgent to identify a more effective therapy for patients with PHN. Methods: Patients who underwent radiofrequency thermocoagulation therapy for PHN were retrospectively reviewed and were divided into a radiofrequency thermocoagulation (CRF) and double neddles radiofrequency thermocoagulation (DCRF). The pain scores (numerical rating scale, NRS) were evaluated at the following time points: before the operation, 1 day, 3 months, 6 months, 1 year, and 2 years after operation. The incidence of complications and the degree of pain relief were evaluated. The in vitro ovalbumin experiment was used to indicate the effects of radiofrequency thermocoagulation. Results: Compared with the preoperative NRS scores, the postoperative NRS scores decreased significantly; the NRS scores of the DCRF group was lower than that of the CRF group at all time points from 6 months to 2 years following the operation. The total effective rate of the DCRF group was significantly higher than that of the CRF group at 2 years following the operation. The incidence of numbness in the DCRF group was higher than that noted in the CRF group. The ovalbumin experiments in vitro indicated that the effects of radiofrequency thermocoagulation were optimal when the distance between the two needles was 5 mm. Conclusions: DCRF with a 5 mm spacing exhibits a longer duration and higher effective rate in the treatment of PHN and is worth promoting.
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