Search

Background: Neuropathic pain is difficult to control and patient response to current treatment is often inadequate. Opioids have been widely used to treat a variety of pain states, but have several side effects. Endogenous opioids are clinically safe, but are not used for treatment because of rapid metabolism. However, in-vivo transfection of endogenous opioid genes could have a powerful and safe analgesic effect. The purpose of this study was to investigate the efficacy of proopiomelanocortin (POMC, a precursor of the endogenous opioid peptide β-endorphin) gene transfer by use of radial shock waves (RSWs) in a rat neuropathic pain model., Methods: As a neuropathic pain model, we used the Bennett chronic constriction injury (CCI) method. Immediately after CCI induction, POMC plasmid was injected into the rats' gastrocnemius muscle followed by exposure to RSW. Mechanical allodynia was measured for 4 weeks and dorsal root ganglion (DRG) neurons were sectioned and immunostained., Results: β-Endorphin blood levels and the number of β-endorphin-immunoreactive (IR) muscle fibers increased over 28 days. β-Endorphin overexpression caused a decrease in the number of calcitonin gene-related peptide (CGRP)-IR DRG neurons and suppressed neuropathic pain induced by CCI without causing adverse side effects. The size-distribution pattern of CGRP-IR DRG neurons shifted from small to large cells in the CCI group; however, the number of both small and large CGRP-IR cells decreased in the POMC group., Conclusion: POMC gene transfection alleviated allodynia and reduced CGRP expression in DRG neurons without adverse effects. CGRP is not produced in large neurons under physiologic conditions; however, in this study CGRP expression was shifted to large neurons after nerve injury. This change in cell-size distribution suggests that CGRP expression in large neurons is related to neuropathic pain. These findings suggest that POMC gene transfection using RSWs is a safe and effective treatment for neuropathic pain.

Background: Nonsteroidal anti-inflammatory drugs (NSAIDs) are commonly used in clinical situations to reduce inflammation and pain. Percutaneous administration is one of the routes mainly used in Japan to deal with the pain from acute injuries, to chronic pain such as chronic low back pain and osteoarthritis (OA). There have been no studies that report the effect of percutaneous administration of NSAIDs on chronic pain in animal models. This study aimed to investigate the effect of percutaneously absorbed NSAIDs on a rodent model of OA., Methods: OA was induced with an intra-articular injection of monoiodoacetate into the right knees (left knee was treated with saline, normal control) of female Sprague-Dawley rats. Physical evaluation, diameter, and the range of motion (ROM) of the knee joint, as well as pain-related behavior, were evaluated. Animals were killed and perfused 7 days after the intra-articular injection, and then local tissue from the knee [for cytokine assay: tumor necrosis factor (TNF)-α, interleukin (IL)-6, and nerve growth factor (NGF)] and spinal cord (immunostained for c-Fos protein reflecting neuronal excitation) were evaluated (n = 7 each). Twenty-eight days after the injection, the other rats were then divided into three groups and were identified by a plaster tape containing an NSAID or a vehicle applied to their OA (ipsilateral) knees: a vehicle-treated group, a loxoprofen-treated (lox) group, and a ketoprofen-treated (ket) group. The behavior elicited by von Frey hairs, inflammatory cytokines, and c-Fos protein at 0, 8, and 24 h after tape application were evaluated (n = 7 each). The plaster tapes contained corresponding NSAIDs used in clinical settings: lox 2.8 mg and ket 1.1 mg. Three of the OA animals were histologically evaluated., Results: As the OA progressed, the ipsilateral knee joint showed OA-like appearance physically and histologically. The knee diameter increased and ROM decreased significantly (P < 0.05), showing histological OA-like cartilage degeneration. Pain threshold decreased significantly according to OA progression (P < 0.05). NSAID application significantly improved the threshold 24 h after application in both the lox and ket groups (P < 0.05) without any significant difference between groups. Cytokine concentrations and c-Fos were significantly suppressed in both lox and ket groups (P < 0.05). Lox suppressed TNF-α and NGF more than ket, whereas ket suppressed IL-6 more., Conclusion: Suppression of proinflammatory cytokines and c-Fos expression by clinically used NSAIDs suggests that their percutaneous administration may have an analgesic effect for treating chronic pain at a molecular level.

Background: Surgery for lumbar spondylolisthesis is widely performed. However, there have been no reports comparing posterolateral and anterior interbody fusion prospectively. We compared instrumented posterolateral fusion with anterior interbody fusion for L4 spondylolisthesis in a prospective study., Methods: Forty-six patients diagnosed with L4 degenerated spondylolisthesis were divided into two groups. Twenty-two consecutive patients underwent non-instrumented anterior interbody fusion using an iliac bone graft (ALIF; L4-L5 level), and 24 consecutive patients underwent instrumented posterolateral fusion with local bone (PLF; L4-L5 level). The rates of bone union, visual analog scale (VAS) score, Japanese Orthopedic Association (JOA) score, Oswestry Disability Index (ODI), surgical invasion, and complications were evaluated before and 2 years after surgery., Results: Age, VAS score, JOA score, and ODI were not significantly different between the two groups before surgery (P > 0.05). Success of bone union between the two groups was not significantly different (P > 0.05). Blood loss during surgery was significantly less; however, periods of bed rest and hospital stay were significantly longer in the ALIF group (P < 0.05). Overall patient satisfaction, and low back and leg pain in both groups were significantly improved after surgery; however, low back pain showed greater improvement in the ALIF group compared with the PLF group (P < 0.05). Complications such as donor site pain (4 patients in the ALIF group) and dural tearing (3 patients in the PLF group) were observed., Conclusions: If single level fusion for L4 spondylolisthesis is performed, both anterior and posterior methods reduce patients' low back and leg pain. Improvement of low back pain was significantly greater after ALIF; however, periods of hospital stay and of bed rest were significantly longer.

Background: It has been reported that rat L5/6 lumbar discs are innervated mainly by L2 dorsal root ganglion neurons. We previously reported that L2 spinal nerve infiltration was effective for discogenic low back pain (DLBP) patients, although the diagnosis was based only on the results of physical examination, plain films, and magnetic resonance imaging (MRI). The purpose of the current study was to evaluate L2 spinal nerve block for DLBP patients retrospectively based on MRI findings and surgical results., Methods: A total of 62 patients with only LBP and no accompanying radicular pain were investigated. Patients had only one level of disc degeneration on MRI. When pain was provoked during discography, we performed surgery at the next stage (40 patients). In all, 22 patients were excluded owing to negative discography results. Of the 40 patients, we evaluated 25 strictly selected patients suffering from DLBP. DLBP was diagnosed when the patient experienced pain relief at least 2 years after anterior lumbar interbody fusion. Fifteen patients who did not show pain relief after surgery were used for the non-DLBP group. L2 spinal nerve infiltration using 1.5 ml of lidocaine was performed in all 40 patients before surgery. The visual analogue scale (VAS) score after L2 spinal nerve infiltration was recorded, and an association of L2 spinal nerve infiltration and DLBP was explored., Results: Low back pain scores assessed using the VAS score, the Japanese Orthopedic Association score, and the Oswestry Disability Index score in the two groups were not significantly different. L 2 spinal nerve infiltration was effective for 27 patients but not effective for 13 patients; the VAS score after 15 min and 2 h improved in the DLBP group compared with that of the non-DLBP group (P < 0. 05). L2 spinal nerve infiltration was more effective in DLBP patients (21 patients, 84%) than in the non-DLBP group (6 patients, 40%) (P < 0.05)., Conclusions: In the current study, L2 spinal nerve infiltration was effective in 84% of selected DLBP patients and is thought to be a useful tool for diagnosing DLBP. However, we should take into consideration that the L2 spinal nerve infiltration was effective in 40% of non-DLBP patients as well.

Background: Recent studies have revealed that the low-affinity nerve growth factor receptor, p75 neurotrophin receptor (p75NTR), is important in inflammatory pain. Moreover, p75NTR immunoreactive sensory nerve and dorsal root ganglion (DRG) neurons have been found to innervate lumbar intervertebral discs. The purpose of the current study was to investigate the effect of p75NTR saporin, a toxin used to destroy p75NTR, on calcitonin gene-related peptide (CGRP), an inflammatory neuropeptide associated with pain, in DRG neurons innervating punctured intervertebral discs in rats., Methods: The neurotracer fluorogold (FG) was applied to the surfaces of L5/6 discs to label their innervating DRG neurons (n = 30). Of 30 rats, 10 were in a nonpunctured disc sham surgery control group (nonpuncture group), and the other 20 were in experimental groups in which intervertebral discs were punctured with a 23-gauge needle. p75NTR saporin was applied to the discs of 10 rats (puncture + p75NTR saporin group) and the other 10 received the same volume of saline (puncture + saline group). At 14 days after surgery, DRGs from L1 to L6 were harvested, sectioned, and immunostained for CGRP, and the proportions of CGRP-immunoreactive DRG neurons was evaluated., Results: Of the FG-labeled neurons innervating the L5/6 disc, the proportion of CGRP-immunoreactive neurons was 32% +/- 6% (mean +/- SE) in the nonpuncture group, 47.2% +/- 8% in the puncture + saline group, and 34.6% +/- 9% in the puncture + p75NTR saporin group. The proportion of CGRP-immunoreactive neurons was significantly greater in the puncture + saline group compared with the nonpuncture and puncture + p75NTR saporin groups (P < 0.01)., Conclusions: Half of the DRG neurons innervating the discs were positive for CGRP in the puncture + saline group. CGRP is important for mediating inflammatory and nerve-injured pain and may be important in discogenic pain. However, p75NTR saporin suppressed CGRP expression in DRG neurons. Therefore, p75NTR may be an important receptor for mediating discogenic pain via CGRP expression.

Background: Clinically, the origin of low back pain is unknown. The pain may originate from the lumbar muscles directly, or it may be referred pain from the spine. Dorsal root ganglion (DRG) neurons with dichotomizing axons have been reported in several species and are thought to be related to referred pain. However, these neurons, which have dichotomizing axons to the lumbar facet joints and to the lumbar muscle, have not been fully investigated., Methods: Two neurotracers - 1,1'-dioctadecyl-3,3,3',3'- tetramethyl-indocarbocyanine perchlorate (DiI) and fluorogold (FG) - were used in the present double-labeling study. DiI crystals were placed in the right L5/6 facet joint, and FG was applied to right multifidus muscles at the L5 level in 10 rats. Two weeks later, bilateral DRGs from L1 through L6 were harvested, sectioned, and observed under a fluorescence microscope., Results: DiI-labeled DRG neurons innervating the L5/6 facet joint (5.17% of the total DRG neurons) were distributed from L1 to L6. FG-labeled DRG neurons innervating the lower back muscle (15.9% of the total) were also distributed from L1 to L6. Double-labeled DRG neurons were found from L1 to L6. The ratio of total double-labeled/total DiI-labeled DRG neurons was 17% and that of total double-labeled/total FG-labeled DRG neurons was 7%. Approximately 17% of all DRG neurons innervating the facet joints had other axons that extended to the lower back muscle., Conclusions: This finding provides a possible neuroanatomical explanation for referred low back muscle pain from the lower facet joints.

Objective: This study aimed to investigate the level of vascular endothelial growth factor (VEGF) in the temporomandibular joint (TMJ) synovial fluid (SF) and the severity of arthroscopically observed synovitis before and after visually guided TMJ irrigation (VGIR) in patients with chronic closed lock (CCL). In addition, the findings were correlated with the clinical outcome., Study Design: Twenty-four patients with unilateral CCL, who underwent a second VGIR either as a repeated therapeutic TMJ irrigation or as a follow-up arthroscopy, were enrolled in the study. They were divided into either successful (s-group; n = 11) and unsuccessful (u-group; n = 13) groups. The VEGF level in the aspirated SF and the severity of synovitis were compared between the s- and u-groups. In each group, the same parameters were compared before and after VGIR. The correlation of the VEGF level with the severity of synovitis was also studied., Results: At the first VGIR, the VEGF levels showed no significant differences when comparing s- and u-groups. At the second VGIR, the VEGF level was significantly higher in the u-group. The VEGF level significantly decreased after the first VGIR in the s-group but remained unchanged in the u-group. There was no significant correlation between the VEGF level and the severity of synovitis., Conclusions: The level of VEGF in TMJ SF seems to reflect the clinical status in patients with CCL. Moreover, VEGF may be an important target molecule in future chemotherapy of TMJ CCL., (Copyright (c) 2010 Mosby, Inc. All rights reserved.)

Objective: This study aimed to investigate the changes of joint effusion (JE) on the MRI and arthroscopically observed pathology after visually guided TMJ irrigation (VGIR) in patients with chronic closed lock. The correlation of these findings to the clinical outcome was also studied., Study Design: Forty patients with unilateral chronic closed lock who underwent 2-time VGIR, were divided into either the good outcome (g-) group (n = 29) or poor outcome (p-) group (n = 11) after the first VGIR. Before each VGIR, the each severity of JE, osteoarthritis, synovitis, and fibrous adhesion were assessed. They were compared between the g- and p-groups, or between the first and second VGIR., Results: The severity of JE at the first VGIR was significantly worse in the p-group. In both groups, JE significantly improved after the first VGIR. In the g-group, synovitis significantly improved after the first VGIR, but fibrous adhesion significantly became worse., Conclusions: JE may be predictive for the clinical outcome of TMJ irrigation in chronic closed lock patients. Moreover, the severity of JE and arthroscopically observed synovitis could reflect the clinical state to some degree.

The membranous urethral muscles, bulbocavernosus muscle (BCM) and ischiocavernosus muscle (ICM) play a significant role on expulsion at ejaculation. Projection of the sympathetic pathways in the retroperitoneum to these muscles was investigated in the dog. Intraluminar pressure of the membranous urethra and contractions of the BCM and ICM to electrical stimulation of the lumbar splanchnic nerve (LSN) or the lumbosacral sympathetic chain (LSC) were examined. Stimulation of the LSN was performed after transection of the unilateral hypogastric nerve (HGN) to clarify its cross-innervation. Stimulation of each of the 2nd to 4th LSNs elicited elevation of the intraluminal pressure of the membranous urethra. In eight dogs whose right HGNs were transected, 15 of the 19 right LSNs, and 12 of the 16 left LSNs examined elicited elevation of the membranous urethral pressure, respectively. In five dogs whose left HGNs were transected, 6 of the 9 right LSNs and 10 of the 12 left LSNs stimulated elicited elevation of the pressure. Stimulation of the HGN caused no detectable contractions of the BCM and ICM in all six dogs examined. Stimulation of the LSC elicited responses of the BCM and ICM in all six dogs examined and the membranous urethra in three of six dogs. The maximum value of the response of the BCM was greater than that of the ICM. After consecutive transection of the ipsilateral pelvic nerve, stimulation of the LSC showed no significant changes in the responses of the BCM and ICM. The above results indicate the following: (1). each of the L2-L4 LSNs sends signals to the membranous urethra via two routes, passing through the ipsilateral or contralateral HGN; (2). the above nerve does not send effective signals to the BCM and ICM; (3). the LSC sends signals to the membranous urethra, BCM and ICM; (4). the signals from the LSC mainly pass through the pudendal nerve to the BCM and ICM; and (5). the signals were dominant to the BCM compared with the ICM.