• The Korean Journal of Pain
• /
• v.35 no.4
• /
• pp.433-439
• /
• 2022

Background: Repeated administration of opioid analgesics for pain treatment can produce paradoxical hyperalgesia via peripheral and/or central mechanisms. Thus, this study investigated whether spinally (centrally) administered orexin A attenuates opioid-induced hyperalgesia (OIH). Methods: [D-Ala², N-Me-Phe⁴, Gly⁵-ol]-enkephalin (DAMGO), a selective µ-opioid receptor agonist, was used to induce mechanical hypersensitivity and was administered intradermally (4 times, 1-hour intervals) on the rat hind paw dorsum. To determine whether post- or pretreatments with spinal orexin A, dynorphin A, and anti-dynorphin A were effective in OIH, the drugs were injected through an intrathecal catheter whose tip was positioned dorsally at the L3 segment of the spinal cord (5 ㎍ for all). Mechanical hypersensitivity was assessed using von Frey monofilaments. Results: Repeated intradermal injections of DAMGO resulted in mechanical hypersensitivity in rats, lasting more than 8 days. Although the first intrathecal treatment of orexin A on the 6th day after DAMGO exposure did not show any significant effect on the mechanical threshold, the second (on the 8th day) significantly attenuated the DAMGO-induced mechanical hypersensitivity, which disappeared when the type 1 orexin receptor (OX1R) was blocked. However, intrathecal administration of dynorphin or an anti-dynorphin antibody (dynorphin antagonists) had no effect on DAMGO-induced hypersensitivity. Lastly, pretreatment with orexin A, dynorphin, or anti-dynorphin did not prevent DAMGO-induced mechanical hypersensitivity. Conclusions: Spinal orexin A attenuates mechanical hyperalgesia induced by repetitive intradermal injections of DAMGO through OX1R. These data suggest that OIH can be potentially treated by activating the orexin A-OX1R pathway in the spinal dorsal horn.

• Restorative Dentistry and Endodontics
• /
• v.49 no.3
• /
• pp.31.1-31.11
• /
• 2024

Objectives: The present study investigated the prevalence of mechanical allodynia (MA) in healthy teeth adjacent and contralateral to endodontically diseased teeth. Materials and Methods: This cross-sectional study included 114 patients with symptomatic irreversible pulpitis and apical periodontitis in permanent mandibular first molars who possessed healthy teeth adjacent and contralateral to the endodontically diseased tooth. The mechanical sensitivity of the teeth was determined by percussion testing. The presence or absence of pain on percussion in the teeth adjacent and contralateral to the endodontically diseased tooth and the tooth distal to the contralateral symmetrical tooth was recorded according to coding criteria. The prevalence of MA was computed as a percentage, and binary logistic regression analysis was done. The Fisher exact test and Mann-Whitney U test were used for binary and ordinal data. Results: Age and sex did not influence the prevalence of MA. An increased prevalence of MA was found in patients with higher levels of spontaneous pain (p < 0.001). The prevalence of allodynia was 57% in teeth adjacent to endodontically diseased teeth and 10.5% in teeth contralateral to endodontically diseased teeth. In addition, on the ipsilateral side, there were more painful sensations distal to the diseased tooth than mesially. Conclusions: Despite being disease-free, teeth adjacent and contralateral to endodontically diseased teeth exhibited pain on percussion. There was a direct association between the severity of the patient's pain and the presence of MA.

• The Korean Journal of Pain
• /
• v.30 no.1
• /
• pp.3-17
• /
• 2017

Background: Postherpetic neuralgia (PHN) is a common and painful complication of acute herpes zoster. In some cases, it is refractory to medical treatment. Preventing its occurrence is an important issue. We hypothesized that applying nerve blocks during the acute phase of herpes zoster could reduce PHN incidence by attenuating central sensitization and minimizing nerve damage and the anti-inflammatory effects of local anesthetics and steroids. Methods: This systematic review and meta-analysis evaluates the efficacy of using nerve blocks to prevent PHN. We searched the MEDLINE, EMBASE, Cochrane Library, ClinicalTrials.gov and KoreaMed databases without language restrictions on April, 30 2014. We included all randomized controlled trials performed within 3 weeks after the onset of herpes zoster in order to compare nerve blocks vs active placebo and standard therapy. Results: Nine trials were included in this systematic review and meta-analysis. Nerve blocks reduced the duration of herpes zoster-related pain and PHN incidence of at 3, 6, and 12 months after final intervention. Stellate ganglion block and single epidural injection did not achieve positive outcomes, but administering paravertebral blockage and continuous/repeated epidural blocks reduced PHN incidence at 3 months. None of the included trials reported clinically meaningful serious adverse events. Conclusions: Applying nerve blocks during the acute phase of the herpes zoster shortens the duration of zoster-related pain, and somatic blocks (including paravertebral and repeated/continuous epidural blocks) are recommended to prevent PHN. In future studies, consensus-based PHN definitions, clinical cutoff points that define successful treatment outcomes and standardized outcome-assessment tools will be needed.

• Biomolecules & Therapeutics
• /
• v.27 no.4
• /
• pp.414-422
• /
• 2019

There is accumulating evidence that microRNAs are emerging as pivotal regulators in the development and progression of neuropathic pain. MicroRNA-15a/16 (miR-15a/16) have been reported to play an important role in various diseases and inflammation response processes. However, whether miR-15a/16 participates in the regulation of neuroinflammation and neuropathic pain development remains unknown. In this study, we established a mouse model of neuropathic pain by chronic constriction injury (CCI) of the sciatic nerves. Our results showed that both miR-15a and miR-16 expression was significantly upregulated in the spinal cord of CCI rats. Downregulation of the expression of miR-15a and miR-16 by intrathecal injection of a specific inhibitor significantly attenuated the mechanical allodynia and thermal hyperalgesia of CCI rats. Furthermore, inhibition of miR-15a and miR-16 downregulated the expression of interleukin-$1{\beta}$ and tumor-necrosis factor-${\alpha}$ in the spinal cord of CCI rats. Bioinformatic analysis predicted that G protein-coupled receptor kinase 2 (GRK2), an important regulator in neuropathic pain and inflammation, was a potential target gene of miR-15a and miR-16. Inhibition of miR-15a and miR-16 markedly increased the expression of GRK2 while downregulating the activation of p38 mitogen-activated protein kinase and $NF-{\kappa}B$ in CCI rats. Notably, the silencing of GRK2 significantly reversed the inhibitory effects of miR-15a/16 inhibition in neuropathic pain. In conclusion, our results suggest that inhibition of miR-15a/16 expression alleviates neuropathic pain development by targeting GRK2. These findings provide novel insights into the molecular pathogenesis of neuropathic pain and suggest potential therapeutic targets for preventing neuropathic pain development.

• The Journal of Internal Korean Medicine
• /
• v.44 no.5
• /
• pp.904-910
• /
• 2023

Objectives: The aim of this case report is to present the effects of Korean medicine treatment in a patient with left facial paraesthesia, temporomandibular joint (TMJ) pain, and post-traumatic neck pain induced by cerebral infarction. Methods: A 26-year-old male patient was treated with Cheongpa-Jeon H, acupuncture, pharmacopuncture (Shinbaro2), and Chuna Therapy for 24 days of hospitalization. Left facial paraesthesia, TMJ pain, and post-traumatic neck pain were assessed with a Numeric Rating Scale (NRS) and EuroQoL-5 Dimension (EQ-5D). Post-traumatic neck pain was assessed using the Neck Disability Index (NDI). Results: After 24 days of treatment, the patient's left facial paraesthesia and left arm tingling sensation were relieved from NRS 6 to NRS 2. Left TMJ pain was reduced from NRS 5 to NRS 2. The EQ-5D score increased from 0.138 to 0.73. The NDI score decreased from 71.11 to 37.78. Conclusion: These results show that left facial paraesthesia, TMJ pain, and post-traumatic neck pain can be relieved with Korean medicine treatment. However, further well-designed studies are required to confirm these findings.

• Childhood Kidney Diseases
• /
• v.23 no.2
• /
• pp.124-127
• /
• 2019

Herlyn-Werner-Wunderlich (HWW) syndrome is a rare congenital anomaly of the genitourinary tract comprising uterus didelphys, obstructed hemivagina, and ipsilateral renal agenesis. Patients with HWW syndrome usually present symptoms such as dysmenorrhea, abdominal pain, pelvic mass, and purulent vaginal discharge. If not treated at an appropriate time, complications such as infertility, endometriosis, pyosalpinx, and subsequent pelvic adhesions may occur. Here, we report a case of HWW syndrome in a 7-year-old-girl who was also diagnosed as having central precocious puberty. She was brought to the pediatric department with chief complaints of lump in her breast and vaginal discharge. When she was around 2 months old, she was confirmed to have a single kidney on ultrasonography. We checked her past medical history and diagnosed her as having HWW syndrome based on the results of imaging studies, including abdominal ultrasonography and pelvic magnetic resonance imaging. She underwent treatment with gonadotropin-releasing hormone analogue for 2 years. During 24 months of follow-up, she showed no serious problems or complications. If renal anomalies are identified immediately after birth or in infancy, further screening tests should be conducted prior to menstruation for determining congenital abnormalities of the reproductive tract and vice versa.

• Journal of Oral Medicine and Pain
• /
• v.34 no.4
• /
• pp.387-395
• /
• 2009

Nerve growth factor (NGF) and sensory neuropeptides are involved in the process of nociception at peripheral nerve fibers and wide spread in central nervous system. The aims of this study were to investigate NGF and sensory neuropeptides (substance P [SP] and calcitonin gene-related peptide [CGRP]) levels in human plasma and saliva, and the associations between these sensory neuropeptides levels and chronic orofacial pain symptoms. NGF, SP, and CGRP levels in plasma and resting whole saliva samples collected from 67 orofacial pain patients (joint pain, dental or periodontal pain, mucosal pain) and 36 pain free control subjects were measured by enzyme immunoassay. The characteristic pain intensity of each subject was measured using the Graded Chronic Pain Scale and the flow rate of resting whole saliva was measured. Joint pain patients group showed significantly higher plasma NGF level compared to each of dental pain patients (p<0.01), mucosal pain patients (p<0.01), and control group (p<0.01). Plasma NGF level of dental pain patients group was significantly higher than that of control group (p<0.01). Saliva SP level of dental pain patients group (p<0.05) and saliva CGRP level of mucosal pain group (p<0.05) were significantly higher than that of control group. Plasma and saliva SP levels of joint pain patients was significantly associated with pain intensity (plasma: standardized coefficient=0.599, p<0.01, saliva: standardized coefficient=0.504, p=0.05). In dental pain patients group, plasma SP (standardized coefficient=0.559, p<0.01), saliva SP (standardized coefficient=0.520, p<0.01) and saliva CGRP (standardized coefficient=0.599, p<0.01) levels were significantly associated with age. In mucosal pain patients group, plasma SP (standardized coefficient=0.495, p<0.05), saliva SP (standardized coefficient=0.500, p<0.05), and saliva CGRP (standardized coefficient=0.717, p<0.01) levels were significantly associated with age. NGF and neuropeptides may play a role in the maintenance of various orofacial pain symptoms. The examination of those levels in plasma and saliva helps understanding the mechanism of orofacial pain, and furthermore, can be applied to the diagnosis and therapy of orofacial pain.

• Journal of Pharmacopuncture
• /
• v.14 no.3
• /
• pp.19-45
• /
• 2011

Objectives: This study was performed to analyse the effects of Sweet Bee Venom(Sweet BV-pure melittin, the major component of honey bee venom) on the central nervous system in rats. Methods: All experiments were conducted at Biotoxtech Company, a non-clinical studies authorized institution, under the regulations of Good Laboratory Practice (GLP). Male rats of 5 weeks old were chosen for this study and after confirming condition of rats was stable, Sweet BV was administered in thigh muscle of rats. And checked the effects of Sweet BV on the central nervous system using the functional observational battery (FOB), which is a neuro-toxicity screening assay composed of 30 descriptive, scalar, binary, and continuous endpoints. And home cage observations, home cage removal and handling, open field activity, sensorimotor reflex test/physiological measurements were conducted. Results: 1. In the home cage observation, there was not observed any abnormal signs in rats. 2. In the observation of open field activity, the reduction of number of unit areas crossed and rearing count was observed caused by Sweet BV treatment. 3. In the observation of handling reactivity, there was not observed any abnormal signs in rats. 4. In the observation of sensorimotor reflex tests/physiological measurements, there was not observed any neurotoxic signs in rats. 5. In the measurement of rectal temperature, treatment of Sweet BV did not showed great influences in the body temperature of rats. Conclusions: Above findings suggest that Sweet BV is relatively safe treatment in the central nervous system. But in the using of over dose, Sweet BV may the cause of local pain and disturbance of movement. Further studies on the subject should be conducted to yield more concrete evidences.

• The Journal of the Society of Stroke on Korean Medicine
• /
• v.17 no.1
• /
• pp.1-8
• /
• 2016

■ Objectives The purpose of this clinical study is to evaluate the effect of Sosiho-tang(小柴胡湯) on a patient with Central fever due to pontine hemorrhage. ■ Methods A patient with central fever diagnosed with pontine hemorrhage was treated with herbal medication, acupuncture, electro-acupuncture(EA). Then we evaluated the improvement by average and peak of each day's body temperature. ■ Results Decrease of average and peak of each day's body temperature were observed after taking Sosiho-tang(小柴胡湯). ■ Conclusion This study proved the effect of moxibustion treatment on left side paresthesia due to central post-stroke pain.

• Journal of Acupuncture Research
• /
• v.21 no.3
• /
• pp.145-167
• /
• 2004

Objective : Neuropathic pain can be caused by a partial peripheral nerve injury. This kind of pain is usually accompanied by spontaneous burning pain, allodynia and hyperalgesia. It is not clear that scolopendrid aqua-acupuncture can control neuropathic pain effectively. The purpose of this study is to examine if scolopendrid aqua-acupuncture may be effective to the neuropathic pain (mechanical allodynia, cold allodynia) in a rat model of neuropathic pain. Methods : To produce the model of neuropathic pain, under isoflurane 2.5% anesthesia, tibial nerve and sural nerve was resected. After the neuropathic surgery, the author examined if the animals exhibited the behavioral signs of allodynia. The allodynia was assessed by stimulating the medial malleolus with von Frey filament and acetone. Three weeks after the neuropathic surgery, scolopendrid aqua-acupuncture was injected at Hwando(GB30) one time a day for one week. After that the author examined the withdrawl response of neuropathic rats' legs by von Frey filament and acetone stimulation. And also the author examined c-fos in the midbrain central gray of neuropathic rats and the change of WBC count in the blood of neuropathic rats. Results & Conclusion : 1. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of mechanical allodynia in SHA-1, SHA-2 and SAH-3 group as compared with control group. 2. The scolopendrid aqua-acupuncture injected at Hwando(GB30) decreased the withdrawl response of chemical allodynia(cold allodynia) in SHA-1, SHA-2 and SAH-3 group as compared with control group. 3. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and control group(p=0.01), sham and SHA-3 group(p=0.026), control group and SHA-1 group(p=0.01), control group and SHA-2 group(p=0.024) in the c-fos expression. 4. The scolopendrid aqua-acupuncture injected at Hwando(GB30) showed the significant difference between sham group and SHA-3 group(p=0.010), control group and SHA-3 group(p=0.006) in the WBC count.