Treatment Of Intervertebral Disc Disease Research Articles

LAMINECTOMIA DORSAL E HEMILAMINECTOMIA TORÁCICAS PARA TRATAMENTO DE EXTRUSÃO DE DISCO INTERVERTEBRAL EM CANINO

Intervertebral disc disease (IVDD) is the most common disc disease in dogs. The diagnosis is based on anamnesis, patient history, neurological examination and imaging tests and the association of these data influences the choice between conservative or surgical treatment. The objective of this report is to present a case of chronic intervertebral disc extrusion, located between thoracic vertebrae, emphasizing the clinical-surgical approach, diagnosis and established therapy. An eight-year-old female Maltese canine was referred for surgical treatment after two years of conservative treatment for IVDD. For better identification of the affected intervertebral spaces, a computed tomography scan was requested and, based on the imaging results, the procedure of hemilaminectomy in vertebrae T8-T9-T10 and dorsal laminectomy in vertebrae T12-T13 was indicated. It is concluded that the association of both surgical techniques achieved multiple decompression of the affected thoracic intervertebral spaces, ensuring better quality of life for the patient.

Leptin accelerates BMSC transformation into vertebral epiphyseal plate chondrocytes by activating SENP1-mediated deSUMOylation of SIRT3.

Bone marrow mesenchymal stem cells (BMSCs) are capable of multidirectional differentiation, and engrafted BMSCs can be used to replace damaged chondrocytes for treatment of intervertebral disc disease. However, chondroblast differentiation of implanted BMSCs is inhibited by the anoxic environment of the articular cavity. Here, we found that leptin enhanced the transformation of BMSCs into chondrocytes under hypoxic conditions. BMSCs isolated from mice were cultured in medium supplemented with leptin under hypoxia. The expression of MFN1/2 and OPA1 were increased only in BMSCs cultured in an anoxic environment. In addition, in hypoxic environments cell energy metabolism relies on glycolysis regulated by leptin, rather than by mitochondrial oxidation. The expression of the de-SUMOylation protease SENP1 was elevated, leading to SIRT3-mediated activation of PGC-1α; these processes were regulated by CREB phosphorylation, and promoted mitochondrial fusion and cell differentiation. The chondrogenic activity of BMSCs isolated from SIRT3-knockout mice was lower than that of BMSCs isolated from wildtype mice. Implantation of SIRT3-knockout murine-derived BMSCs did not significantly improve the articular cartilage layer of the disc. In conclusion, the hypoxic microenvironment promoted BMSC differentiation into chondrocytes, whereas osteoblast differentiation was inhibited. SENP1 activated SIRT3 through the deSUMOylation of mitochondria and eliminated the antagonistic effect of SIRT3 acetylation on phosphorylation. When phosphorylation activity of CREB was increased, phosphorylated CREB is then transferred to the nucleus, affecting PGC-1α. This promotes mitochondrial fusion and differentiation of BMSCs. Leptin not only maintains chondrogenic differentiation homeostasis of BMSCs, but also provides energy for differentiation of BMSCs under hypoxic conditions through glycolysis.

UBR3 promotes inflammation and apoptosis via DUSP1/p38 pathway in the nucleus pulposus cells of patients with intervertebral disc degeneration.

Intervertebral disc disease (IDD) is a primary cause of low back pain, affecting 5% of individuals. Previous study have shown that dual-specificity (Thr/Tyr) phosphatase 1 (DUSP1) regulates p38 MAPK activity and DUSP1 level is regulated by ubiquitination. As an E3 ubiquitin-protein ligase, UBR3 has been shown to regulate a variety of biological processes through ubiquitination. However, the role of UBR3/DUSP1/p38 in IDD remains to be elucidated. In the current study, we found that UBR3 was significantly increased in the nucleus pulposus tissues of IDD patients and was correlated with IDD severity. Silencing UBR3 promoted the growth, inhibited apoptosis, and inhibited inflammation in primary NPCs. Mechanism study suggested that UBR3 exerted its effects through p38. Co-immunoprecipitation assay indicated that UBR3 promoted DUSP1 ubiquitination. Overexpression of DUSP1 reversed the effect of UBR3 overexpression. Our data also supported that UBR3 was positively correlated with p-p38, but negatively correlated with DUSP1 in IDD. In summary, UBR3 promotes inflammation and apoptosis via inhibiting the p38 signaling pathway by DUSP1 ubiquitination in the NPCs of IDD patients. These findings highlight the importance of UBR3/DUSP1/p38 signaling pathway in IDD and provide new insights for the prevention and treatment of IDD.

Randomized controlled trial of pregabalin for analgesia after surgical treatment of intervertebral disc disease in dogs.

To assess the effect of perioperative pregabalin on pain behavior in dogs after intervertebral disc surgery. Prospective, randomized, controlled clinical trial with a blinded observer. Forty-six client-owned dogs undergoing intervertebral disc surgery. Dogs were randomly assigned to two groups, with the placebo group receiving opioids alone and the pregabalin group receiving opioids plus pregabalin. Opioid analgesia consisted of 0.6 mg/kg l-methadone given intravenously at anesthetic induction, followed by 0.2 mg/kg given at 8, 16, and 24 hours after extubation and fentanyl patches applied at the end of surgery. Pregabalin was given orally (4 mg/kg) 1 hour before anesthesia, followed by postoperative treatment three times per day (4 mg/kg) for 5 days. The outcome measures were the treatment-group differences in peri-incisional mechanical sensitivity and Glasgow Composite Measure Pain Scale (CMPS-SF) assessed during the first 5 postoperative days. Pregabalin serum concentrations were measured after 24, 72, and 120 hours. Pregabalin reduced pain levels in the treatment group by a mean of 2.5 CMPS-SF units (95% confidence interval [CI] = -3.19 to -1.83, P < .001) compared with the control group during the study period. Pregabalin increased the mechanical nociceptive threshold by a mean of 6.89 N per day (95% CI = 1.87-11.92, P < .001) and of 7.52 N per day (95% CI = 2.29-12.77, P < .001) during the study period, depending on location. Mean levels of serum pregabalin were 5.1, 4.71, and 3.68 μg/mL at 24, 72, and 120 hours postoperatively, respectively. Postoperative signs of pain after surgical treatment of intervertebral disc herniation (IVDH) were reduced when dogs received perioperative pregabalin rather than opioids alone. Perioperative pregabalin reduces postoperative pain after surgical treatment of IVDH.

Butyrate alleviates inflammatory response and NF-κB activation in human degenerated intervertebral disc tissues

Butyrate has multiple protective effects in inflammation-related intestinal diseases. Previous studies have found that butyrate could inhibit inflammation in rheumatoid arthritis. Inflammation is a pivotal inducement in the degeneration progress of the intervertebral disc. The anti-inflammatory treatment has an apparent curative effect in the symptomatic treatment of spine-related disease. Herein we investigated whether butyrate plays a protective role in degenerated intervertebral disc model. To mimic the lumbar disc local inflammatory environment, human primary nucleus pulposus cells were cultured with interleukin-1β (IL-1β, 10 ng/ml) to build a nucleus pulposus cell inflammation model. Butyrate was added to the cell culture medium to test the effect of butyrate on disc inflammation. Furthermore, a cultured nucleus pulposus tissue model was treated with butyrate (1 mM) to simulate the local treatment of intervertebral disc disease. Herein, we found that butyrate could downregulate the production of the inflammatory mediator caused by IL-1β stimulation in the cell culture model. Additionally, butyrate inhibits the secretion of pro-inflammatory cytokines or graded enzymes in disc tissues from lumbar disc herniation patients. Furthermore, the anti-inflammatory function of butyrate in lumbar disc degenerated model may be caused by inhibiting the activation of the nuclear factor kappa B (NF-κB) signal pathway. This study presents butyrate as a candidate therapeutic method to treat lumbar disc degenerative disease.

Treatment of Intervertebral Disc Disease by Regenerative Medicinal Techniques

Treatment of Intervertebral Disc Disease by Regenerative Medicinal Techniques

Treatment of Intervertebral Disk Disease by the Administration of mRNA Encoding a Cartilage-Anabolic Transcription Factor

Intervertebral disk (IVD) degeneration is often associated with severity of lower back pain. IVD core is an avascular, highly hydrated tissue composed of type II collagen, glycosaminoglycans, and proteoglycans. The disk degeneration is not only a destruction of IVD structure but also is related to a disorder of the turnover of the disk matrix, leading the jelly-like IVD core to be replaced by fibrous components. Here we present a disease-modifying strategy for IVD degenerative diseases by direct regulation of the cells in the IVD using mRNA medicine, to alter the misbalanced homeostasis during disk degeneration. When mRNA encoding a cartilage-anabolic transcription factor, runt-related transcription factor-1, was administered to a rat model of coccygeal disk degeneration using a polyplex nanomicelle composed of polyethylene glycol-polyamino acid block copolymers and mRNA, the disk height was maintained to a significantly higher extent (≈81%) compared to saline control (69%), with prevention of fibrosis in the disk tissue. In addition, the use of nanomicelles effectively prevented inflammation, which was observed by injection of naked mRNA into the disk. This proof-of-concept study revealed that mRNA medicine has a potential for treating IVD degenerative diseases by introducing a cartilage-anabolic factor into the host cells, proposing a new therapeutic strategy using mRNA medicine.

Canine chondrodystrophic intervertebral disc disease (Hansen type I disc disease)

Intervertebral disc disease (IVDD) is the most common spinal disease in dogs. Chondrodystrophic dogs, which have disproportionably short and curved limbs, are predisposed to Hansen type I IVDD and of these the miniature Dachshund is over represented [1,2], is more likely to be presented at an earlier age [3] and is at greater risk of a severe spinal cord injury [4]. The tendency for IVDD in Dachshunds is inherited [5,6] and a major locus on chromosome 12 harbours genetic variations affecting the development of intervertebral disc calcification [7]. Hansen type I disc degeneration is thought to occur because of loss of notochordal cells which produce proteoglycans which “hold water” in the disc. Chondrodystrophic dogs have a primary deficiency of notochordal cells, a study found that large notochordal cells in the nucleus pulposus of chondrodystrophoid dogs formed 13% of the cell population in young dogs and fell to 0.4% in adults, whereas they were the predominant cell type in the nonchondrodystrophoid dogs at all ages [8]. Thus chondrodystrophoid dogs suffer early degenerative changes in the disc and a concomitant reduction in proteoglycan content, increased collagen, and loss of water content making the discs likely to herniate [8]. Certain lifestyle factors may increase or decrease risk of IVDD and this is currently under investigation. There is a suggestion that exercise (including stair climbing) reduces the incidence of disc calcification [9]. By contrast it has been hypothesized that obesity/lack of postural muscle strength may increase risk. Dachshunds with intervertebral disc extrusion had significantly smaller cross sectional area and greater fat infiltration in the epaxial muscles (muscles which lie dorsal to the horizontal septum of the vertebrae which mobilize and globally stabilize the trunk [10]) compared to dogs presenting with fibrocartilagenous embolism (another acute onset intervertebral disc related spinal disease) [11]. In addition chondrodystrophic dogs may have increased risk of IVVD if they have a more extreme conformation e.g. Dachshunds that have a longer back and shorter limbs are more at risk [12] and breeds with a comparatively heavy head such as the Bassett Hound may be more at risk of cervical disc disease. Breeds with a tendency for kyphoscoliosis such as the French Bulldog may be more at risk of IVDD in the IVDs adjacent to a vertebral malformation [13,14]. This presentation details the pathogeneis, clinical presentation, diagnosis and treatment of IVDD in chondrodystrophic dogs.

Hemilaminectomy for Herniated Discs at the Cervicothoracic Junction in a Beagle Dog

A 7-year-old, female Beagle dog presented with a primary complaint of severe neck pain and paretic gait. A lesion was suspected between C6 and T2 on the basis of neurological examinations. Magnetic resonance imaging of the cervicothoracic spine revealed herniation of disc material from the C7-T1 intervertebral space resulting in marked spinal cord compression. Hemilaminectomy was performed to treat the intervertebral disc disease at C7-T1. Treatment was effective and the clinical condition of the dog was remarkably improved. This result suggests that hemilaminectomy is an effective option for surgical treatment of intervertebral disc disease at the cervicothoracic junction in dogs.

COMPARISON BETWEEN COMPUTED TOMOGRAPHY, FLUOROSCOPY, AND ULTRASONOGRAPHY FOR GUIDING PERCUTANEOUS INJECTION OF THE CANINE INTERVERTEBRAL DISC

A minimally invasive method for delivering injectable therapeutic agents would be desirable for the treatment of intervertebral disc disease in dogs. The purpose of this study was to compare computed tomography (CT), ultrasonography (US), and fluoroscopy modalities for guiding percutaneous injection into canine intervertebral discs. Intervertebral discs of 14 dog cadavers were injected with a gelified ethanol therapeutic agent. Successful injectate placement and injectate leakage were determined based on necropsy inspection of discs. Injection into the nucleus pulposus was successful in 55 of 78 (71%) of all injected discs. Injections guided using CT and fluoroscopy were significantly more successful than US-guided injections. Odds of successful injection without leakage were greater for CT vs. US (P = 0.0026) but there was no significant difference between CT and fluoroscopy (P = 0.0620). Injection success rates did not differ among vertebral sites or dog cadavers of varying weights. Forty-nine (63%) of injection sites had injectate leakage outside the disc and 10 of these involved structures within the vertebral canal. The highest rate of injection success with the least amount of leakage was achieved with CT guidance. Findings indicated that CT, fluoroscopy, and US are feasible modalities for guiding percutaneous injection of a gelified ethanol therapeutic agent into the canine intervertebral disc, with moderate to high success rates for different regions of the spine. However, a moderately high rate of injectate leakage occurred outside of the disc and this should be taken into consideration for future safety and efficacy studies.

Comparison of Two Minimally Invasive Approaches to the Thoracolumbar Spinal Canal in Dogs

To describe 2 minimally invasive approaches to the spinal canal for treatment of intervertebral disc disease and compare their efficacy to conventional hemilaminectomy. Experimental; randomized, controlled design. Canine cadavers (n = 10; 5 small and 5 large dogs). Barium-impregnated agarose gel (BA-gel) was injected into the spinal canal at 3 intervertebral spaces of the thoracolumbar spine in each cadaver. Sites were randomly assigned to 1 of 3 approaches: conventional (standard) hemilaminectomy (SH), endoscopic foraminotomy (EF), or foraminotomy via an illuminated port (FP). Computed tomographic scans were performed before and after the procedures. Procedures were compared for duration, bone window size, incision length, complications and percentage of BA-gel removed via repeated measures ANOVA. The incisions created during EF and FP were similar and smaller to that of a SH. The duration of EF was prolonged compared to FP and SH. The size of the vertebral window created was greater after SH in large dogs, while no difference was found between procedures in small dogs. The amount of simulated disc material removed from the spinal canal did not differ between procedures, regardless of the size of the dog. The two minimally invasive approaches were feasible in small and large dogs. Both techniques allowed similar removal of simulated disc material and may decrease soft tissue morbidity compared to SH.

Incidence of and risk factors for postoperative pneumonia in dogs anesthetized for diagnosis or treatment of intervertebral disk disease

To determine incidence of and risk factors for postoperative pneumonia in dogs anesthetized for diagnosis or treatment of intervertebral disk disease (IVDD). Retrospective case-control study. 707 dogs that underwent general anesthesia for the diagnosis or treatment of IVDD between 1992 and 1996 or between 2002 and 2006. Postoperative pneumonia was diagnosed if compatible clinical signs (cough or hypoxemia) and radiographic abnormalities (alveolar infiltrates) developed within 48 hours after anesthesia. To identify risk factors for postoperative pneumonia, findings for dogs that developed postoperative pneumonia between 2002 and 2006 were compared with findings for a randomly selected control group of unaffected dogs from the same population. There were no significant differences in age, breed, body weight, sex, location of IVDD, or survival rate between the 2 time periods, but there were significant differences in the use of magnetic resonance imaging, computed tomography, and hemilaminectomy and in the percentage of dogs that developed postoperative pneumonia in the later (4.6%) versus the earlier (0.6%) years. Significant risk factors for postoperative pneumonia included preanesthetic tetraparesis, cervical lesions, undergoing magnetic resonance imaging, undergoing > 1 anesthetic procedure, longer duration of anesthesia, and postanesthetic vomiting or regurgitation. Results suggested that at this institution, the incidence of postoperative pneumonia in dogs anesthetized for diagnosis or treatment of IVDD had increased in recent years.

Complications Related to Surgical Treatment of Intervertebral Disc Disease in Dogs

After intervertebral disk surgery we often have to deal with various complications (seizures, gastrointestinal tract (GIT) ulcerations, cystitis, and surgical wound healing problems). These complications may lead to the death of the patient. We performed clinical and laboratory investigations in 161 dogs with an intervertebral disc disease. After that, we performed a cranial (n = 31), caudal (n = 125) or both (n = 5) types of myelography at the same time, and surgery - ventral slot decompression (SLOT) (n = 18) or hemilaminectomy (n = 143). During the postsurgical period we observed seizures, GIT complications, cystitis, and surgical wound healing problems or even death of the patients. These complications appeared to be related to the lesion site, the degree of clinical signs and the type of surgical procedure. In our study we found a higher incidence of seizures after cranial myelography, higher incidence of gastrointestinal (GI) complications particularly in paraplegic dogs, and a higher risk of death in patients after the SLOT surgery. The occurrence of cystitis was not significant (p = 0.5524, p = 0.1655, respectively). We consider seizures, GI ulcerations, and death the most frequent complications after intervertebral disc surgery. Their incidence depends on the lesion site and the degree of neurologic symptoms.

Transplantation of mesenchymal stem cells embedded in Atelocollagen ® gel to the intervertebral disc: a potential therapeutic model for disc degeneration

Intervertebral disc degeneration is considered to be one of the major causes of low back pain. Despite this irreversible phenomenon, attempts to decelerate disc degeneration using various techniques have been reported. However, to date there has been no proven technique effective for broad clinical application. Based on previous studies, we hypothesize that maintenance of proteoglycan content in the disc is achieved by avoiding the depletion of nucleus pulposus and preserving the structure of the annulus is a primary factor in decelerating disc degeneration. One novel approach to solve the dilemma of intervertebral disc degeneration is found at the stem cell level. Mesenchymal stem cells (MSCs) are known to possess the ability to differentiate into various kinds of cells from mesenchymal origin. Although the majority of cells that contribute to disc formation are known to obtain chondrocyte-like phenotypes, no reported study has emphasized the correlation with mesenchymal stem cells. To evaluate the possible potential of MSCs in disc cell research and treatment of degenerative disc disease, autologous MSCs embedded in Atelocollagen ® gel were transplanted into the discs of rabbits which had undergone a procedure proven to induce degeneration. The results suggest that MSC transplantation is effective in decelerating disc degeneration in experimental models and provided new hopes for treatment of degenerative disc disease in humans. Atelocollagen ® gel served as an important carrier of MSCs in transplantation, permitting proliferation, matrix synthesis and differentiation of MSCs. This study strengthens the viable efficacy of practical application of MSCs in treatment of intervertebral disc disease.

Biochemical injection treatment for discogenic low back pain: a pilot study

Background context: Biochemical treatment options including attempts at intervertebral disc restoration are desirable for the physiologic treatment of degenerative disc disease. Purpose: This was a pilot study to test the potential effectiveness of intradiscal injection therapy using agents known to induce proteoglycan synthesis in the treatment of intervertebral disc disease. Study design: Prospective, within subject, experimental design was applied in the study. Patient sample: Thirty patients, average age 46.5 years, with chronic intractable low back pain of 8.5 years average duration, took part in the study. All patients had lumbar discography with reproduction of pain. Outcome measures: Pretreatment Roland-Morris disability scores and visual analogue scores were compared with 1-year follow-up posttest values of these scores. Methods: Lumbar intervertebral discs were injected with a solution of glucosamine and chondroitin sulfate combined with hypertonic dextrose and dimethlysulfoxide (DMSO). Assessment of pain and disability was completed before treatment and an average of 12 months after the last treatment. Results: Posttreatment Roland-Morris scores for the entire group of 30 patients of 6.4±.994 were significantly (p<.001) lower than pretreatment scores of 12.0±.92 (mean±SE). The posttreatment visual analogue scores of 3.00±.44 were also significantly less than the pretreatment of 6.11±.33 (mean±SE). Although the results were statistically significant for the 30 patients as a whole, 17 of the 30 patients (57%) improved markedly with an average of 72% improvement in disability scores and 76% in visual analogue scores. The other 13 patients (43%) had little or no improvement. Patients who did poorly included those with failed spinal surgery, spinal stenosis and long-term disability. There were no complications or serious side effects, although postinjection pain was moderate to severe for 48 to 72 hours and required epidural steroids in five cases. Conclusions: The results of this pilot study suggest that intradiscal injection therapy with glucosamine, chondroitin sulfate, hypertonic dextrose and DMSO warrants further evaluation with randomized controlled trials.

Nursing the Dog with Intervertebral Disc Disease

Intervertebral disc (IVD) disease is the most common spinal disease in dogs. The veterinary nurse plays an important role in treating patients with this disease, as good nursing care and physiotherapy are paramount for ensuring a satisfactory clinical outcome. In the second of two articles, Clare Rusbridge discusses aspects of nursing the spinal patient. Pathophysiology, clinical signs and treatment of IVD disease were reviewed in the last issue.

Chemonucleolysis for treatment of intervertebral disk disease

Chemonucleolysis for treatment of intervertebral disk disease

Late results of treatment of intervertebral disc disease with chymopapain.

The authors report a 12-year follow-up review of 33 patients treated with chymopapain (Discase) injection for intervertebral disc disease. This carefully controlled series of patients was treated under local anesthesia in the prone position. Only the single offending disc that correlated with the myelographic and clinical pathology (without the use of discography) was injected with Discase. Anaphylaxis is treated instantly at the first sign of disturbance, and no patients suffered shock. The percentage of patients who were completely cured or improved continues at about 70%. Aside from sensitivity, complications attributable to proper use of the enzyme remain at zero. Follow-up review of those patients over 10 years would indicate that there is no risk of delayed organ toxicity, no risk of carcinogenesis, and no apparent risk of first-generation teratogenesis.

Evaluation of Dorsal Column Stimulation in the Treatment of Chronic Pain

Abstract Dorsal column stimulation (DCS) was used in the treatment of chronic intractable pain in 51 patients. Twenty-five of the patients had back and leg pain secondary to the treatment of intervertebral disc disease; 11 had postoperative pain after general or thoracic surgical procedures. The remainder suffered pain related to multiple sclerosis, spinal cord injury, carcinoma, and peripheral vascular disease. Pain had been present for a mean of 24 months. Thirty-seven patients underwent DCS electrode placement by open laminectomy, and 11 had percutaneous epidural DCS electrode placement. Three patients first underwent epidural DCS electrode implantation and subsequently had DCS electrode implantation by laminectomy. No major complications were noted, although multiple lesser complications required 33 additional operative procedures for correction. Follow-up periods ranged from 12 to 67 months, with a mean of 38 months. Immediately after implantation. 47% of the patients reported that they had essentially complete pain relief, but 3 years later this had decreased to 8%. No patient followed for 4 years or longer reported complete pain relief. Thirty-three per cent of the patients discontinued the regular use of narcotics for pain relief after DCS electrode implantation. Unfortunately, only 16% were able to return to gainful employment or full physical activity after DCS. Based on these data and a review of the literature, the following conclusions are made: (a) assessment of success in the treatment of chronic pain is strongly dependent on the criteria used for patient evaluation: (b) with the criteria of this report, DCS is a relatively ineffective treatment for chronic pain; (c) epidural percutaneous DCS systems are no more effective than are those placed by laminectomy, and, because of technical problems with epidural systems (mainly lead breakage and migration), the latter may actually be less effective; and (d) at present DCS seems to play a minor role in the treatment of chronic intractable pain.

The Double Blind Study Comparing Disease to Placebo

The authors participated in a double blind study on the effectiveness of chymopapain in the treatment of intervertebral disc disease. Results of the double blind study indicated that chymopapain was no more effective than a placebo. The authors challenge the validity of the double blind study because of timing of result evaluation, possible therapeutic activities of the placebo utilized, and possible insufficient dose of chymopapain.