Objective: Valproic acid (VPA), as known as histone deacetylase inhibitor, has neuroprotective effects. This study investigated the histological changes and functional recovery from spinal cord injury (SCI) associated with VPA treatment in a rat model. Methods: Locomotor function was assessed according to the Basso-Beatlie-Bresnahan scale for 2 weeks in rats after receiving twice daily intraperitoneal injections of 200 mg/kg VPA or the equivalent volume of normal saline for 7 days following SCI. The injured spinal cord was then examined histologically, including quantification of cavitation. Results: Basso-Beatlie-Bresnahan scale scores in rats receiving VPA were significantly higher than in the saline group (p<0.05). The cavity volume in the VPA group was Significantly reduced compared with the control (saline-injected) group (p<0.05). The level of histone acetylation recovered in the VPA group, while it was significantly decreased in the control rats (p<0.05). The macrophage level was significantly decreased in the VPA group (p<0.05). Conclusion: VPA influences the restoration of hyperacetylation and reduction of the inflammatory reaction resulting from SCI, and is effective for histology and motor function recovery.
Myong-Hwan Karm;Hyun-Jung Kwon;Euiyong Shin;Honggyoon Bae;Young Ki Kim;Seong-Soo Choi
The Korean Journal of Pain
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제36권4호
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pp.441-449
/
2023
Background: Hypertonic saline is used for treating chronic pain; however, clinical studies that aid in optimizing therapeutic protocols are lacking. We aimed to determine the concentration of intrathecally injected hypertonic saline at which the effect reaches its peak as well as the underlying γ-aminobutyric acid (GABA) receptor-related antinociceptive mechanism. Methods: Spinal nerve ligation (SNL; left L5 and L6) was performed to induce neuropathic pain in rats weighing 250-300 g. Experiment 1: one week after implanting the intrathecal catheter, 60 rats were assigned randomly to intrathecal injection with 0.45%, 0.9%, 2.5%, 5%, 10%, and 20% NaCl, followed by behavioral testing at baseline and after 30 minutes, 2 hours, 1 day, and 1 week to determine the minimal concentration which produced maximal analgesia. Experiment 2: after determining the optimal intrathecal hypertonic saline concentration, 60 rats were randomly divided into four groups: Sham, hypertonic saline without pretreatment, and hypertonic saline after pretreatment with one of two GABA receptor antagonists (GABAA [bicuculline], or GABAB [phaclofen]). Behavioral tests were performed at weeks 1 and 3 following each treatment. Results: Hypertonic saline at concentrations greater than 5% alleviated SNL-induced mechanical allodynia and had a significant therapeutic effect, while showing a partial time- and dose-dependent antinociceptive effect on thermal and cold hyperalgesia. However, pretreatment with GABA receptor antagonists inhibited the antinociceptive effect of 5% NaCl. Conclusions: This study indicates that the optimal concentration of hypertonic saline for controlling mechanical allodynia in neuropathic pain is 5%, and that its analgesic effect is related to GABAA and GABAB receptors.
Purpose: The purpose of this study was to examine effects of nitric oxide synthase (NOS) inhibitor on muscle weight and myofibrillar protein content of affected and unaffected hindlimb muscles in rats with neuropathic pain induced by unilateral peripheral nerve injury. Methods: Neuropathic pain was induced by ligation and cutting of the left L5 spinal nerve. Adult male Sprague-Dawley rats were randomly assigned to one of two groups: The NOSI group (n=19) had NOS inhibitor (L-NAME) injections daily for 14 days, and the Vehicle group (n=20) had vehicle injections daily for 14 days. Withdrawal threshold, body weight, food intake and activity were measured every day. At 15 days all rats were anesthetized and soleus, plantaris and gastrocnemius muscles were dissected from hindlimbs. Muscle weight and myofibrillar protein content of the dissected muscles were determined. Results: The NOSI group showed significant increases as compared to the Vehicle group for body weight at 15 days, muscle weight and myofibrillar protein content of the unaffected soleus and gastrocnemius. The NOSI group demonstrated a higher pain threshold than the vehicle group. Conclusion: NOSI for 14 days attenuates unaffected soleus and gastrocnemius muscle atrophy in neuropathic pain model.
Background: Transforaminal epidural steroid injections are known to reduce inflammation by inhibiting synthesis of various proinflammatory mediators and have been used increasingly. The anti-inflammatory properties of opioids are not as fully understood but apparently involve antagonism sensory neuron excitability and pro-inflammatory neuropeptide release. To date, no studies have addressed the efficacy of transforaminal epidural morphine in patients with radicular pain, and none have directly compared morphine with a tramadol for this indication. The aim of this study was to compare morphine and tramadol analgesia when administered via epidural injection to patients with lumbar radicular pain. Methods: A total of 59 patients were randomly allocated to 1 of 2 treatment groups and followed for 3 months after procedure. Each patient was subjected to C-arm guided transforaminal epidural injection (TFEI) of an affected nerve root. As assigned, patients received either morphine sulfate (2.5 mg/2.5 ml) or tramadol (25 mg/0.5 ml) in combination with 0.2% ropivacaine (1 ml). Using numeric rating scale was subsequently rates at 2 weeks and 3 months following injection for comparison with baseline. Results: Both groups had significantly lower mean pain scores at 2 weeks and at 3 months after treatment, but outcomes did not differ significantly between groups. Conclusions: TFEI of an opioid plus local anesthetic proved effective in treating radicular pain. Although morphine surpassed tramadol in pain relief scores, the difference was not statistically significant.
Percutaneous osteoplasty (POP) is defined as the injection of bone cement into various painful bony lesions, refractory to conventional therapy, as an extended technique of percutaneous vertebroplasty (PVP). POP can be applied to benign osteochondral lesions and malignant metastatic lesions throughout the whole skeleton, whereas PVP is restricted to the vertebral body. Common spinal metastases occur in the thoracic (70%), lumbosacral (20%), and cervical (10%) vertebrae, in order of frequency. Extraspinal metastases into the ribs, scapulae, sternum, and humeral head commonly originate from lung and breast cancers; extraspinal metastases into the pelvis and femoral head come from prostate, urinary bladder, colon, and uterine cervical cancers. Pain is aggravated in the dependent (or weight bearing) position, or during movement (or respiration). The tenderness and imaging diagnosis should match. The supposed mechanism of pain relief in POP is the augmentation of damaged bones, thermal and chemical ablation of the nociceptive nerves, and local inhibition of tumor invasion. Adjacent (facet) joint injections may be needed prior to POP (PVP). The length and thickness of the applied needle should be chosen according to the targeted bone. Bone cement is also selected by its osteoconduction, osteoinduction, and osteogenesis. Needle route should be chosen as a shortcut to reach the target bony lesions, without damage to the nerves and vessels. POP is a promising minimally invasive procedure for immediate pain relief. This review provides a technical survey for POPs in painful bony lesions.
Background: Transcutaneous electrical nerve stimulation (TENS), manual acupuncture (MA), and spinal cord stimulation (SCS) are used to treat a variety of pain conditions. These non-pharmacological treatments are often thought to work through similar mechanisms, and thus should have similar effects for different types of pain. However, it is unclear if each of these treatments work equally well on each type of pain condition. The purpose of this study was to compared the effects of TENS, MA, and SCS on neuropathic, inflammatory, and non-inflammatory pain models. Methods: TENS 60 Hz, 200 ㎲, 90% motor threshold (MT), SCS was applied at 60 Hz, an intensity of 90% MT, and a 0.25 ms pulse width. MA was performed by inserting a stainless-steel needle to a depth of about 4-5 mm at the Sanyinjiao (SP6) and Zusanli (ST36) acupoints on a spared nerve injury (SNI), knee joint inflammation (3% carrageenan), and non-inflammatory muscle pain (intramuscular pH 4.0 injections) in rats. Mechanical withdrawal thresholds of the paw, muscle, and/or joint were assessed before and after induction of the pain model, and daily before and after treatment. Results: The reduced withdrawal thresholds were significantly reversed by application of either TENS or SCS (P < 0.05). MA, on the other hand, increased the withdrawal threshold in animals with SNI and joint inflammation, but not chronic muscle pain. Conclusions: TENS and SCS produce similar effects in neuropathic, inflammatory and non-inflammatory muscle pain models while MA is only effective in inflammatory and neuropathic pain models.
Lee, Jaehyung;Lee, Eugene;Lee, Joon Woo;Kang, Yusuhn;Ahn, Joong Mo;Kang, Heung Sik
Journal of Korean Neurosurgical Society
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제63권6호
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pp.747-756
/
2020
Objective : To evaluate the effectiveness and long-term outcome predictors of percutaneous sacroplasty (PSP). Methods : This single-center study assessed 40 patients with sacral insufficiency fractures using the short-axis technique under C-arm flat-panel detector computed tomography (CT). Two radiologists reviewed the patients' magnetic resonance and CT images to obtain imaging findings before PSP and determine technical success, respectively. The short-term outcomes were visual analog scale score changes and opioid usage reductions. Long-term outcomes were determined using telephone interviews and the North American Spine Society (NASS) patient-satisfaction index at least one year after PSP. Results : Technical success was achieved without any significant complications in 39 patients (97.5%). Telephone interviews were possible with 12 patients and failed in 10 patients; death was confirmed in 18 patients. Fifteen patients (50%) re-visited the hospital and received conservative treatment, including spinal injections. Nine patients reported positive satisfaction (NASS patient-satisfaction index 1 or 2), while the negative satisfaction group (NASS patient-satisfaction index 3 or 4, n=3) showed a higher incidence of compression fractures at the thoracolumbar spine level (66.7% vs. 22.2%) and previous spinal injection history (66.7% vs. 33.3%). The poor response group also showed higher incidences of facet joint arthrosis (100% vs. 55.6%), central canal stenosis (100% vs. 22.2%), neural foraminal stenosis (33.3% vs. 22.2%), scoliosis (100% vs. 33.3%), and sagittal malalignment (100% vs. 44.4%). Conclusion : PSP was effective for sacral insufficiency fractures and showed good long-term outcomes. Combined compression fractures in the thoracolumbar spine and degenerative lumbar pathologies could be possible poor outcome predictors.
Kim, Min Joon;Lee, Ji Hwan;Jang, Jo Ung;Quan, Fu Shi;Kim, Sun Kwang;Kim, Woojin
The Korean Journal of Physiology and Pharmacology
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제21권6호
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pp.657-666
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2017
Paclitaxel, a chemotherapeutic drug, induces severe peripheral neuropathy. Gabapentin (GBT) is a first line agent used to treat neuropathic pain, and its effect is mediated by spinal noradrenergic and muscarinic cholinergic receptors. Electro-acupuncture (EA) is used for treating various types of pain via its action through spinal opioidergic and noradrenergic receptors. Here, we investigated whether combined treatment of these two agents could exert a synergistic effect on paclitaxel-induced cold and mechanical allodynia, which were assessed by the acetone drop test and von Frey filament assay, respectively. Significant signs of allodynia were observed after four paclitaxel injections (a cumulative dose of 8 mg/kg, i.p.). GBT (3, 30, and 100 mg/kg, i.p.) or EA (ST36, Zusanli) alone produced dose-dependent anti-allodynic effects. The medium and highest doses of GBT (30 and 100 mg/kg) provided a strong analgesic effect, but they induced motor dysfunction in Rota-rod tests. On the contrary, the lowest dose of GBT (3 mg/kg) did not induce motor weakness, but it provided a brief analgesic effect. The combination of the lowest dose of GBT and EA resulted in a greater and longer effect, without inducing motor dysfunction. This effect on mechanical allodynia was blocked by spinal opioidergic (naloxone, $20{\mu}g$), or noradrenergic (idazoxan, $10{\mu}g$) receptor antagonist, whereas on cold allodynia, only opioidergic receptor antagonist blocked the effect. In conclusion, the combination of the lowest dose of GBT and EA has a robust and enduring analgesic action against paclitaxel-induced neuropathic pain, and it should be considered as an alternative treatment method.
Background: Epidural steroid injections (ESI) are a common treatment for spinal disorders. Previous research has shown that aspiration of the syringe is not a sensitive test for placement of an intravascular needle. Serious complications have been reported from injection of steroids and local anesthetics into the vascular space. In addition to safety concerns, the efficacy may decline with partial injection outside the desired epidural location. We hypothesized that incidence of vascular problems is increased in patients who undergo spine surgery compared with the patients who don't undergo spine surgery. We investigated the incidence of vascular problems during lumbosacral transforaminal ESI and we compared the difference of vascular problems between the patients who undergo spinal surgery and those patients who don't undergo spinal surgery. Methods: Two hundreds and three patients were consecutively recruited and they received 299 fluoroscopically guided lumbosacral transforaminal ESIs. Injection of contrast was performed under live dynamic fluoroscopy with using digital substraction analysis. The observed uptake pattern was classified into one of three categories: flashback, aspirated, and positive contrast with negative flashback and aspiration. Results: The vascular incidence rate was 20.4%. Transforaminal ESIs performed at S1 had avascular incidence rate of 27.8% compared with 17.7% for all the other lumbar injection sites. The sensitivity of spontaneous observation of blood in the needle hub or blood aspirate for predicting an intravascular injection in lumbar transforaminal ESIs was 70.4%. Conclusions: There is a high incidence of intravascular problems when performing transforaminal ESIs, and this is significantly increased in patients with previous spine surgery. Using a flash or blood aspiration to predict an intravascular injection is not sensitive therefore; a negative flash or aspiration is not reliable. Fluoroscopically guided procedures without contrast confirmation are prone to instill medications intravascularly. This finding confirms the need for not only fluoroscopic guidance, but also for contrast injection instillation when performing lumbosacral transforaminal ESIs, and especially for patients with previous spine surgery.
Lee, Ho-Jin;Ju, Jiyoun;Choi, Eunjoo;Nahm, Francis Sahngun;Choe, Ghee Young;Lee, Pyung Bok
The Korean Journal of Pain
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제34권4호
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pp.394-404
/
2021
Background: We aimed to investigate the effect of epidural polydeoxyribonucleotide (PDRN) on mechanical allodynia and motor dysfunction in a rat model of lumbar foraminal stenosis (LFS). Methods: This study was conducted in two stages, using male Sprague-Dawley rats. The rats were randomly divided into eight groups. In the first stage, the groups were as follows: vehicle (V), sham (S), and epidural PDRN at 5 (P5), 8 (P8), and 10 (P10) mg/kg; and in the second stage, they were as follows: intraperitoneal PDRN 8 mg/kg, epidural 3,7-dimethyl-1-propargilxanthine (DMPX) (0.1 mg/kg), and DMPX (0.1 mg/kg). The LFS model was established, except for the S group. After an epidural injection of the test solutions, von Frey and treadmill tests were conducted for 3 weeks. Subsequently, histopathologic examinations were conducted in the V, S, P5, and P10 groups. Results: A total of 65 rats were included. The P8 and P10 groups showed significant recovery from mechanical allodynia and motor dysfunction at all time points after drug administration compared to the V group. These effects were abolished by concomitant administration of DMPX. On histopathological examination, no epineurial inflammation or fibrosis was observed in the epidural PDRN groups. Conclusions: Epidural injection of PDRN significantly improves mechanical allodynia and motor dysfunction in a rat model of LFS, which is mediated by the spinal adenosine A2A receptor. The present data support the need for further research to determine the role of epidural PDRN in spinal stenosis treatment.
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