STUDY DESIGN: Preliminary clinical trial. PURPOSE: To determine the safety and initial efficacy of intradiscal injection of autologous platelet-rich plasma (PRP) releasate in patients with discogenic low back pain. OVERVIEW OF LITERATURE: PRP, which is comprised of autologous growth factors and cytokines, has been widely used in the clinical setting for tissue regeneration and repair. PRP has been shown in vitro and in vivo to potentially stimulate intervertebral disc matrix metabolism. METHODS: Inclusion criteria for this study included chronic low back pain without leg pain for more than 3 months; one or more lumbar discs (L3/L4 to L5/S1) with evidence of degeneration, as indicated via magnetic resonance imaging (MRI); and at least one symptomatic disc, confirmed using standardized provocative discography. PRP releasate, isolated from clotted PRP, was injected into the center of the nucleus pulposus. Outcome measures included the use of a visual analog scale (VAS) and the Roland-Morris Disability Questionnaire (RDQ), as well as X-ray and MRI (T2-quantification). RESULTS: Data were analyzed from 14 patients (8 men and 6 women; mean age, 33.8 years). The average follow-up period was 10 months. Following treatment, no patient experienced adverse events or significant narrowing of disc height. The mean pain scores before treatment (VAS, 7.5±1.3; RDQ, 12.6±4.1) were significantly decreased at one month, and this was generally sustained throughout the observation period (6 months after treatment: VAS, 3.2±2.4, RDQ; 3.6±4.5 and 12 months: VAS, 2.9±2.8; RDQ, 2.8±3.9; p<0.01, respectively). The mean T2 values did not significantly change after treatment. CONCLUSIONS: We demonstrated that intradiscal injection of autologous PRP releasate in patients with low back pain was safe, with no adverse events observed during follow-up. Future randomized controlled clinical studies should be performed to systematically evaluate the effects of this therapy.
Cytokines ; Female ; Follow-Up Studies ; Humans ; In Vitro Techniques ; Intercellular Signaling Peptides and Proteins ; Intervertebral Disc ; Intervertebral Disc Degeneration ; Leg ; Low Back Pain* ; Magnetic Resonance Imaging ; Male ; Metabolism ; Outcome Assessment (Health Care) ; Platelet-Rich Plasma* ; Regeneration ; Visual Analog Scale

We investigated the role of the central MAPK pathways in extra-territorial (referred) pain resulting from inflammation of the temporomandibular joint (TMJ). Experiments were carried out on male Sprague-Dawley rats weighing 220-280 g. Under anesthesia, these animals were injected with 50 microL of complete Freund's adjuvant (CFA) into the TMJ using a Hamilton syringe. In the control group, saline was injected into the TMJ. To identify the extent of inflammation of the TMJ, Evans blue dye (0.1%, 5 mg/kg) was injected intravenously at 1, 3, 6, 9, 12 and 15 days after CFA injection. The concentration of Evans blue dye in the extracted TMJ tissue was found to be significantly higher in the CFA-treated animals than in the saline-treated group. Air-puff thresholds in the vibrissa pad area were evaluated 3 days before and at 3, 6, 9, 12, 15 and 18 days after CFA injection into the TMJ. Referred mechanical allodynia was established at 3 days, remained until 12 days, and recovered to preoperative levels at 18 days after CFA injection. This referred mechanical allodynia was observed in contralateral side area. To investigate the role of central MAPK pathways, MAPK inhibitors (10 microg) were administrated intracisternally 9 days after CFA injection. SB203580, a p38 MAPK inhibitor, significantly attenuated referred mechanical allodynia, as compared with the vehicle group. PD98059, a MEK inhibitor, also reduced CFA-induced referred mechanical allodynia. These results suggest that TMJ inflammation produces extra-territorial mechanical allodynia, and that this is mediated by central MAPK pathways.
Anesthesia ; Animals ; Evans Blue ; Flavonoids ; Freund's Adjuvant ; Humans ; Hyperalgesia ; Imidazoles ; Inflammation ; Male ; p38 Mitogen-Activated Protein Kinases ; Pain, Referred ; Pyridines ; Rats ; Rats, Sprague-Dawley ; Syringes ; Temporomandibular Joint

The isoflavonol glycoside Talosin A, genistein (GT)-7-alpha-L-6-deoxy talopyranose (GT-Tal), was first isolated from the culture broth of Kitasatospora kifunensis MJM341. The aim of the present study was to evaluate the oral absorption and metabolism of the newly isolated isoflavonol glycoside, GT-Tal compared to genistin (GT-7-O-beta-D-glucopyranoside; GT-Glu). Free GT-Glu and GT-Tal could not be detected prior to enzymatic hydrolysis of the corresponding conjugates in rat plasma. Following oral administration of GT-Tal (15 min), GT-Tal was rapidly absorbed through the gastrointestinal tract and metabolized into GT-Tal conjugates with a mean Cmax of 2.74 microg/mL. GT-Tal was further metabolized to its aglycone, free GT and conjugated GT. After oral administration, GT-Glu was absorbed after being convereted to its aglycone and then further metabolized into its conjugate metabolites (free GT with a mean Cmax of 0.24 mg/mL at 1.25 h; conjugated GT with a mean Cmax of 1.31 mg/mL at 2.00 h). Significant differences in absorption and metabolism of GT-Tal and GT-Glu were observed. GT-Tal was metabolized into its corresponding conjugates or underwent deglycosylation to form GT, whereas GT-Glu was metabolized into its aglycone, GT.
Actinobacteria/*chemistry ; Administration, Oral ; Animals ; Area Under Curve ; Glycosides/administration & dosage/*metabolism/pharmacokinetics ; Hydrolysis ; Intestinal Absorption ; Isoflavones/administration & dosage/*metabolism/pharmacokinetics ; Male ; Random Allocation ; Rats ; Rats, Sprague-Dawley

Among the various sacral fixation techniques used to enhance the strength of fixation, S1 screw placement in the sacrum is the most common method. Ventrolateral S1 screw placement through the sacral ala has been used alone or in combination with a medially-directed screw in the S1 pedicle to enhance pull-out resistance. Although the anatomical safe zone was identified, there is a risk of neurovascular injury particularly when the enhancement of fixation strength requires bicortical purchase. The purpose of this cadaver study is to re-evaluate the previous anatomical safe zone when using an S1 screw laterally directed toward the sacral ala. After dissecting the lateral safe zone of sacral ala in 12 human cadavers, K-wires were intentionally inserted deep into this zone. Each "safe" angle to the center of the safe zone was measured and the degree of risk to neurovascular structures was recorded on the basis of the distance in millimeters from the tips of the penetrating K-wires. The results are as follows: the mean safe angle to the center of the anatomical safe zone was 33.5degrees+/-9.3(20-50). Between 20 and 50 degrees, the range of safe angle was too wide. The distance between the tip of the K-wire and the sacroiliac joint, lumbosacral trunk, obturator nerve was 4.8mm+/-1(4-7.5), 6.8mm+/-1(6-9.5) and 6.8mm+/-3.2(0-10) respectively, while the anterior height between sacral cortex and lumbosacral trunk, internal iliac vein was 0mm and 2.1mm+/-1.8(0-5) respectively. In 29% of cases, the iliolumbar artery, the first branch of the internal iliac artery, abnormally crossed the middle of the safe zone. The sacroiliac joint, lumbosacral trunk, internal iliac vein and iliolumbar artery were at risk from laterally-directed S1 screws. This study shows that bicortical placement of S1 screws into the sacral ala presents unnecessary risks to neurovascular structures. It is concluded that the previous anatomical safe zone for bicortical S1 screw placement into the sacral ala was not surgically safe, and when lumbosacral fixation surgery is planned, operative techniques other than bicortical screw placement should be considered.
Arteries ; Cadaver ; Humans ; Iliac Artery ; Iliac Vein ; Intention ; Obturator Nerve ; Sacroiliac Joint ; Sacrum

The L-gulono-gamma-lactone oxidase gene (Gulo) encodes an essential enzyme in the synthesis of ascorbic acid from glucose. On the basis of previous findings of bone abnormalities in Gulo-/- mice under conditions of ascorbic acid insufficiency, we investigated the effect of ascorbic acid insufficiency on factors related to bone metabolism in Gulo-/- mice. Four groups of mice were raised for 4 weeks under differing conditions of ascorbic acid insufficiency, namely, wild type; ascorbic acid-sufficient Gulo-/- mice, 3-week ascorbic acid-insufficient Gulo-/- mice, and 4-week ascorbic acid-insufficient Gulo-/- mice. Four weeks of ascorbic acid insufficiency resulted in significant weight loss in Gulo-/- mice. Interestingly, average plasma osteocalcin levels were significantly decreased in Gulo-/- mice after 3 weeks of ascorbic acid insufficiency. In addition, the tibia weight in ascorbic acid-sufficient Gulo-/- mice was significantly higher than that in the other three groups. Moreover, significant decreases in trabecular bone volume near to the growth plate, as well as in trabecular bone attachment to the growth plate, were evident in 3- or 4-week ascorbic acid-insufficient Gulo-/-. In summary, ascorbic acid insufficiency in Gulo-/- mice results in severe defects in normal bone formation, which are closely related to a decrease in plasma osteocalcin levels.
Animals ; Ascorbic Acid* ; Down-Regulation* ; Glucose ; Growth Plate ; L-Gulonolactone Oxidase ; Metabolism ; Mice ; Osteocalcin* ; Osteogenesis* ; Plasma ; Tibia ; Weight Loss