• The Korean Journal of Physiology and Pharmacology
• /
• 제1권3호
• /
• pp.251-262
• /
• 1997

Peripheral nerve injury sometimes leads to neuropathic pain and depletion of calcitonin gene related-peptide (CGRP) and substance P (SP) in the spinal cord. However, the pathophysiological mechanisms for depletion of CGRP and SP following the neurorathic injury are still unknown. This study was performed to see whether the distribution of immunoreactivity for CGRP and SP in the superficial dorsal horn and dorsal root ganglia(DRG) was related to the distance between the DRG and injury site. To this aim, we compared two groups of rats; one group was subjected to unilateral inferior and superior caudal trunk transections at the level between the S3 and S4 spinal nerves (S34 group) and the other group at the levels between the S1 and S2, between S2 and S3 and between S3 and S4 spinal nerve (S123 group). The transections in both groups equally eliminated the inputs from the tail to the S1-3 DRG, but the distance from the S1/S2 DRG to the injury site was different between the two groups. Immunostaining with SP and CGRP antibody was done in the S1-S3 spinal cord and DRG of the two groups 1 and 12 weeks after the injury. The results obtained are as follows: 1. The immunoreactivity for CGRP and SP in the ipsilateral superficial dorsal horn and DRG decreased 1 and 12 weeks after neuropathic nerve injury. 2. The immunoreactive area of SP and CGRP in the S1 dorsal horn was smaller in the S123 group than in the S34 group, whereas that in the S3 dorsal horn was not significantly different between the two groups. The number of SP-immunoreactive DRG cells decreased on the neuropathic side as compared to the sham group's in all DRGs of experimental groups except the S1 DRG of the S34 group. These results suggest that the amounts of SP and CGRP in the dorsal horn and DRG following neuropathic injury inversely decrease according to the distance between the DRG and injury site.

• The Journal of Korean Physical Therapy
• /
• 제21권2호
• /
• pp.117-124
• /
• 2009

Purpose: This study examined the effects of swimming exercise and Achyranthes Radix extracts on the inflammatory and behavioral responses in type II collagen-induced arthritic rats for 28 days. Methods: Sprague-Dawley rats were allocated randomly to one of the following four groups: only type II collageninduced (group Ⅰ), application of swimming exercise after type II collagen-induced (group II), application of Achyranthes Radix ointment after type II collagen-induced (group III), application of swimming exercise and Achyranthes Radix ointment after type II collagen-induced (group IV). Arthritis was established in SD rats by an intradermal injection of Chick type II collagen plus incomplete Freund's adjuvant at the base of the tail of the animals. The swimming exercise program consisted of a 25 min swimming session/day with a load corresponding to 5.5% of the weight bearing, three days/week for four weeks. The Achyranthes Radix ointment (0.1g) was applied twice a day for five days. The changes in behavior, H & E stain, and cyclooxygenase-2 (COX-2) level in the knee joint were assessed. Results: The gross and histological examination, after RA induction showed reddening, edema and erythema. The H & E stain revealed the destruction of articular cartilage, bony erosion and the infiltration of inflammatory cells after RA induction. The mechanical allodynia test results were significantly higher in group I than in groups II, III and IV (p<0.01). The immunohistochemistrical response of COX-2 in the knee joint showed that groups II, III, IV had a lower response effect than group I. Conclusion: Swimming exercise training and Achyranthes Radix ointment decreased the inflammatory responses and enhanced the behavioral responses in the arthritic rats.

• The Korean Journal of Pain
• /
• 제6권2호
• /
• pp.275-279
• /
• 1993

Reflex sympathetic dystrophy is a syndrome characterized by persistent, burning pain, hyperpathia, allodynia & hyperaesthesia in an extremity, with concurrent evidence of autonomic nervous system dysfunction. It generally develops after nerve injury, trauma, surgery, et al. The most successful therapies are directed towards blocking the sympathetic intervention to the affected extremity by regional sympathetic ganglion block or Bier block with sympathetic blocker; other traditional treatments include transcutaneous electrical stimulation, immobilization with cast & splint, physical therapy, psychotherapy, administration of sympathetic blocker, calcitonin, corticosteroid and analgesic agents. The purpose of this report is to evaluate and describe the effects of magnetic resonance following unsatisfactory results with traditional treatments of RSD. A 17 year old female patient, 1 year earlier, had received excision and drainage of pus at the right femoral triangle due to an injury caused by a stone. Afterwards, she experienced burning pain, knee joint stiffness, and muscle dystrophy of the right thigh, especially when standing and walking. Despite a year of number of traditional treatments such as: lumbar sympathetic block, continuous epidural analgesia, transcutaneous electrical stimulation, & administration of predisolone, her pain did not improve. Surprisingly, the patients was able to walk free from pain and difficulty after just one application of magnetic resonance. The patient has been successfully treated with further treatment of two to three times a week for approximately ten weeks. More recently, magnetic resonance has been demonstrated to produce effective results for the relief of pain in a variety of diseases. From our experiences we recognize magnetic resonance as a therapeutic modality which can provide excellent results for the treatment of RSD. It has been suggested that polysynaptic reflex which are disturbed in RSD may be modulated normally on the spinal cord level through the application of magnetic resonance.

• Journal of Acupuncture Research
• /
• 제30권3호
• /
• pp.125-134
• /
• 2013

Objectives : We studied the effects of electro and laser acupuncture treatment with $GB_{39}$ and $GB_{34}$ on neuropathic pain in rats induced by tibial and sural nerve ligation. Methods : To produce the model of neuropathic pain, the tibial and sural nerves of rats were ligated by a 6-0 silk thread. Three days after the neuropathic surgery, only electro acupuncture(EA), electro acupuncture and 830 nm laser acupuncture(EA-LA-1), and electro acupuncture and 904 nm laser acupuncture(EA-LA-2) were treated with $GB_{39}$ and $GB_{34}$ twice a week for 8 weeks. We observed the withdrawal response of neuropathic rats' legs by von Frey filament and acetone stimulation. We also observed c-fos and nocieptin on the central gray area in the midbrain of neuropathic rats. Results : As we observed the effect of mechanical allodynia, the EA and EA-LA-1 groups in 5 and 6 weeks and the EA-LA-2 group in 6 weeks increased significantly compared with the control group. As for the effect of c-fos activity in the central gray region, the EA, EA-LA-1, and EA-LA-2 groups decreased significantly compared with the control group. The EA-LA-2 group increased significantly compared with the control group as regards the effect of nociceptin activity in the central gray region. Conclusions : We noticed the synergic effect of electro and laser acupuncture treatment because the EA-LA-1 and EA-LA-2 groups had more controllable effect compared with the control group. This study can be used in clinical therapy for neuropathic pain.

• 대한약침학회지
• /
• 제4권2호
• /
• pp.95-103
• /
• 2001

Background : Central poststroke pain(CPSP) can occur as a result of lesion or dysfunction of the brain from stroke and may cause many difficulty in the social activities and daily life. In this study, we evaluate the clinical effectiveness of east-west medical management for CPSP through VAS(visual analogue scale), infrared themography, MBI(Moderfied Barthel Index) and Rankin scale. Methods : We treated thirty patients with oriental medical treatment method and western & oriental medical treatment method. Each group has fifteen patients of the CPSP. We evaluated their pain(characterizes tingling and burning sensation, aching, hyperalgesia, and allodynia) through VAS(visual analog scale) pain score, the skin temperature of pain site by infrared thermography and assessed their mobility & rehabilitation ability through MBI(Moderfied Barthel Index), Rankin scale before and after pain treatment. Results : The skin temperature of pain site was lower than non-pain site. The difference of skin temperature improved from $0.65{\pm}0.45^{\circ}C$ to $0.39{\pm}0.25^{\circ}C$ after oriental medical treatment and $0.68{\pm}0.54^{\circ}C$ to $0.27{\pm}0.24^{\circ}C$ after western & oriental medical treatment VAS scores improved from $7.9{\pm}1.4$ to $4.7{\pm}1.6$ after oriental medical treatment and $8.1{\pm}1.3$ to $4.6{\pm}1.2$ after western & oriental medical treatment. MBI scores improved from $61.40{\pm}13.58$ to $85.00{\pm}13.85$ after oriental medical treatment and $52.26{\pm}13.52$ to $77.13{\pm}12.04$ after western & oriental medical treatment. And Rankin scale scores improved from $3.33{\pm}0.72$ to $2.46{\pm}0.74$ after oriental medical treatment and $3.60{\pm}0.82$ to $2.66{\pm}0.81$ after western & oriental medical treatment Conclusion : The difference of skin temperature and Rankin scale scores more significantly improved after western & oriental medical treatment than oriental medical treatment. According to the results, we thought east-west medical management is very useful treatment for CPSP and rehabilitation of the patients with stroke.

• Biomolecules & Therapeutics
• /
• 제27권4호
• /
• 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 Korean Journal of Pain
• /
• 제34권1호
• /
• pp.58-65
• /
• 2021

Background: Supraspinal delivery of neurotensin (NTS), which may contribute to the effect of a systemically administered agonist, has been reported to be either pronociceptive or antinociceptive. Here, we evaluated the effects of systemically administered NTSR1 agonist in a rat model of neuropathic pain and elucidated the underlying supraspinal mechanism. Methods: Neuropathic pain was induced by L5 and L6 spinal nerve ligation in male Sprague-Dawley rats. The effects of intraperitoneally administered NTSR1 agonist PD 149163 was assessed using von Frey filaments. To examine the role of 5-HT neurotransmission, a serotonin (5-HT) receptor antagonist dihydroergocristine was pretreated intrathecally, and spinal microdialysis studies were performed to measure the change in extracellular level of 5-HT in response to PD 149163 administration. To investigate the supraspinal mechanism, NTSR1 antagonist 48692 was microinjected into the rostral ventromedial medulla (RVM) prior to systemic PD 149163. Additionally, the effect of intrathecal DHE on intra-RVM PD 149163 was assessed. Results: Intraperitoneally administered PD 149163 exhibited a dose-dependent attenuation of mechanical allodynia. This effect was partially reversed by intrathecal pretreatment with dihydroergocristine and was accompanied by an increased extracellular level of 5-HT in the spinal cord. The PD 149163-produced antinociception was also blocked by intra-RVM SB 48692. Direct injection of PD 149163 into the RVM mimicked the maximum effect of the same drug delivered intraperitoneally, which was reversed by intrathecal dihydroergocristine. Conclusions: These observations indicate that systemically administered NTSR1 agonist produces antinociception through the NTSR1 in the RVM, activating descending serotonergic projection to release 5-HT into the spinal dorsal horn.

• The Korean Journal of Pain
• /
• 제34권1호
• /
• pp.27-34
• /
• 2021

Background: Chemotherapy-induced peripheral neuropathy (CIPN) is a major reason for stopping or changing anticancer therapy. Among the proposed pathomechanisms underlying CIPN, proinflammatory processes have attracted increasing attention. Here we assessed the role of prostaglandin D2 (PGD2) signaling in cisplatin-induced neuropathic pain. Methods: CIPN was induced by intraperitoneal administration of cisplatin 2 mg/kg for 4 consecutive days using adult male Sprague-Dawley rats. PGD2 receptor DP1 and/or DP2 antagonists were administered intrathecally and the paw withdrawal thresholds were measured using von Frey filaments. Spinal expression of DP1, DP2, hematopoietic PGD synthase (H-PGDS), and lipocalin PGD synthase (L-PGDS) proteins were analyzed by western blotting. Results: The DP1 and DP2 antagonist AMG 853 and the selective DP2 antagonist CAY10471, but not the DP1 antagonist MK0524, significantly increased the paw withdrawal threshold compared to vehicle controls (P = 0.004 and P < 0.001, respectively). Western blotting analyses revealed comparable protein expression levels in DP1 and DP2 in the spinal cord. In the CIPN group the protein expression level of L-PGDS, but not of H-PGDS, was significantly increased compared to the control group (P < 0.001). Conclusions: The findings presented here indicate that enhanced PGD2 signaling, via upregulation of L-PGDS in the spinal cord, contributes to mechanical allodynia via DP2 receptors in a cisplatin-induced neuropathic pain model in rats, and that a blockade of DP2 receptor activation may present a novel therapeutic target for managing CIPN.