BACK PAIN, DISC PROLAPSE, FAILED BACK SURGERY - OXYMED HYPERBARIC OXYGEN THERAPY TIER 2
Our originating work using Tier 2 HBOT - Disc Prolapse, Chronic Pain Syndromes, Failed Back Surgical Syndrome (Hooper 1996)
10th International Hyperbaric Medical Symposium 2016 USA - Malcolm R. Hooper Australia
Hyperbaric Oxygen (HBO) - ‘intermittent, short term, high dose Oxygen inhalation’.
HBO is a method of safely delivering high doses of Oxygen to the body. It is done by breathing 100% O2 through a mask or hood while inside a pressurized air chamber.
The pressure (1.75-2.0ATA) inside the chamber causes the (100%) Oxygen you breathe to be dissolved at greater levels in your blood is the same way that pressure causes carbon dioxide to be dissolved in soft drinks. The net effect is to increase Oxygen concentrations (tension) within the blood, which is then driven into the ‘targeted tissue’.
HBO is provided daily and the typical baseline within an initial therapeutic window is between 40-60 and up to an initial 80-100 hours (depending on complexity and chronicity) to promote stabilisation. Complex cases including failed back surgery often require a greater period during the initial intensive saturation.
Integrative Medicine & Lifestyle changes including Ketogenic Diet - you must change your diet and reduce inflammatory acidosis.
Chronic Back Pain and Cytokines - Tumor Necrosis Factor Alpha is a 'pro-inflammatory' cytokine produced by monocyte and macrophage white blood cells which acts as the master regulator of the human inflammatory response.
HBO combined with Low Dose Naltrexone, NAC, MSM and targeted peptides including Etanercept to down regulate (block) TNF-alpha and other proinflammatory markers causing the Cytokine inflammatory cascade.
Antibiotics or viral based therapy depending on blood investigations.
Peptides including BPC157, Cerebrolysin (Brain Derived Neurotrophic Factor) etc (medical referral required).
HBO upregulates the effects and delivery of targeted peptides and supplements. All therapeutic agents require Oxygen as a carrier. Inadequate tissue Oxygen is the basis of many disorders. HBO ensures that target tissues are fully exposed to the benefits of drug and supportive therapies.
Does antibiotic or anti-viral medication reduce your back pain?
* Blood investigations may include specific testing for Mycoplasma profile, Chlamydia profile, Rickettsia profile, Herpes strains, Cytomegalovirus, Epstein Barr Virus, Borrelia species (Lyme Disease). Chlamydia pneumonia and other chronic anaerobic based infections are associated with arthritis and chronic pain syndromes. Opportunistic Infections act as a 'triggering agent' driving chronic pain cycles and progressive degeneration. Chlamydia Pneumonia and chronic diseases.
** If you are considering the antibiotic approach, then ask your doctor to trial Minocycline which elevate IL10, IL4, IL15 (pro anti-inflammatory cytokines - 'good guys')
Med Hypotheses. 2020 Feb 10;138:109617. doi: 10.1016/j.mehy.2020.109617. [Epub ahead of print]
Hyperbaric oxygen treatment: A complementary treatment modality of Modic changes?
Modic changes (MCs) have attracted great interest in recent years. The complex process of MC development and progression seems to involve interplay between mechanical, infective, inflammatory, and degenerative processes that cannot be clearly differentiated. Based on signal intensity on T1- and T2-weighted MRI scans, MCs can be divided three types: Type 1, Type 2, and Type 3.
Predominantly Type 1 MCs are commonly associated with chronic low back pain that is unresponsive to classic treatment options. Infection with low-virulent anaerobic microorganisms, most commonly Propionibacterium acnes, has been implicated in MC development following a disc herniation when a tear enables bacteria to enter the disc.
Recent studies in patients with chronic low back pain following a lumbar disc herniation associated with Type 1 MCs have reported promising results following prolonged systemic antibiotic treatment with amoxicillin-clavulanate.
Hyperbaric oxygen therapy, as primary or adjuvant treatment in association combination with systemic antibiotics or anti-inflammatory therapy, could offer important advantages in treating patients with suspected low-virulent disc infections due to anaerobic microorganisms associated with Type 1 MCs.
We believe that hyperbaric oxygenation could contribute to faster resolution of Type 1 MCs and associated pain through multiple effects-including direct antimicrobial effects through formation of reactive oxygen species (ROS), altering the favorable low oxygen tension milieu such that it becomes unfavorable for bacterial growth and survival, and anti-biofilm effects.
Additionally, hyperbaric oxygenation could contribute to faster pain resolution via direct and indirect anti-inflammatory effects. As an adjuvant treatment administered in combination with systemic antibiotics, HBOT could increase the sensitivity of Propionibacterium acnes to antimicrobial drugs under hyperoxic conditions, resulting in faster MC resolution.
Overall, the faster infection resolution, diminished bacterial load, and anti-inflammatory effects due to reduced cytokine expression and levels of infectious by-products could lead to faster pain resolution following HBOT, and a significant improvement of quality of life in these patients.
Minocycline modulates cytokine and gene expression profiles in the brain after whole-body exposure to radiation.
Author information - Chan Shun Pavilion, Room A-1010, 11175 Campus Street, Loma Linda University, Loma Linda, CA 92354, U.S.A. email@example.com.
An effective countermeasure against radiation damage to normal tissues is urgently needed. The major goal of the present study was to determine if minocycline could modify the immunomodulatory effects of radiation on the brain. C57BL/6 mice were treated with minocycline intraperitoneally for 5 days beginning immediately before total-body exposure to 0, 1, 2 and 3 Gray (Gy) (60)Co γ-rays. Brains were collected on days 4 and 32 post-irradiation for cytokine and gene analyses.
Minocycline treatment significantly increased the levels of interleukin (IL)-10, IL-15 and vascular endothelial growth factor (VEGF) in the brain on day 4 in one or more irradiated groups compared to radiation-alone (p<0.05). IL-10 is anti-inflammatory, IL-15 can prevent apoptosis and VEGF is neuroprotective. On day 32, the drug decreased IL-1β in the 2- Gy group (p<0.05 vs. 2-Gy alone); this cytokine is implicated in immune-related central nervous system pathologies. Microarray analysis of brains on day 32 showed that while radiation increased expression of inflammatory genes such as Il1f10, Il17, Tnfrsf11b, Tnfsf12, Il12b and Il1f8, these were no longer up-regulated in the minocycline-treated groups. Similarly, the pro-apoptotic gene Bik and nitric oxide synthase producer (Nostrin) were no longer up-regulated in the drug-treated groups. Pathway analysis based on gene data suggested that catenin-β1 and tumor suppressor-related transcription regulation were significantly activated by radiation and/or minocycline (activation z-score >2.0). Overall, the data warrant further testing of minocycline as a potential neuroprotectant against radiation-induced damage.
Cytokine Gene Expression Biomarkers
Elevated pro-inflammatory markers Cytokines, Growth Factors, Interleukins are linked with chronic and progressive neurodegenerative disease and often referred to as a Cytokine (Metabolic) Storm leading to multisystem inflammatory cascade.
* Cytokine imbalances are known to be involved in multiple autoimmune disorders, chronic pain syndromes, chronic infections, metabolic disorders, atopic conditions as well as neuropsychiatric disorders.
** Cytokine Interleukin 6 (IL6) can increase up to a 1,000-fold during trauma, infection and elevated in chronic disc pathology.
Cytokines are chemical messengers that primarily signal the immune system and also play a role as neuromodulators. They can be defined as either pro-inflammatory or anti-inflammatory.
Cytokines are signalling proteins and glycoproteins that mediate and regular immunity, inflammation and hematopoiesis. They are also involved in cell growth and differentiation, cell death, angiogenesis, normal development and neuromodulations.
Cytokines are critical to the functional both innate (cell-mediated) and adaptive (antigen specific/humoral) immune systems.
* Pro-inflammatory cytokines include: IL1, IL6, IL7, IL8, IL12 & TNF-α.
** Anti-inflammatory cytokines include: IL4, IL5, IL10, IL12, IL13.
* Interferon-Gamma (INFγ) is a biomarker and often elevated in response to anti TNF therapies and is a biomarker of positive cytokine therapies.
** Tumour Necrosis Factor TNFα is a master regulator of inflammation and associated with multiple autoimmune inflammatory disorders and disease processes.
GM-CSF (Granulocyte Macrophage Colony Stimulating Factor), IFNγ (Interferon Gamma), IL-1, IL-2, IL-4, IL-5, IL-6, IL-7, IL-8, IL-10, IL-12, IL-13, TNFα (Tumour Necrois Factor alpha), TNFβ (Tumour necrosis factor beta), TGFβ (Transforming growth factor beta)
** The combination effects of hypoxia, inflammatory interleukins (IL1, IL6, IL7, IL8), TNFα, co-infections, hi glucose & carbohydrate diet all contribute to the metabolic state referred to as the Cytokine Storm - the precise FUEL for chronic infections, disease progression and autoimmune disorders (multisystem erosion).
Post-traumatic arthritis (PTA) develops after an acute direct trauma to the joints. PTA causes about 12% of all osteoarthritis cases, and a history of physical trauma may also be found in patients with chronic inflammatory arthritis.
* Symptoms include swelling, synovial effusion, pain and sometimes intra-articular bleeding.
Usually, PTA recoveries spontaneously, but the persistence of symptoms after 6 months may be considered pathological and so-called chronic PTA. A variety of molecular, mechanobiological and cellular events involved in the pathogenesis and the progression of PTA have been identified. The activation of inflammatory mechanisms during the PTA acute phase appears to play a critical role in the chronic disease onset. Human studies and experimental models have revealed that a series of inflammatory mediators are released in synovial fluid immediately after the joint trauma. These molecules have been proposed as markers of disease and as a potential target for the development of specific and preventative interventions. Currently, chronic PTA cannot be prevented, although a large number of agents have been tested in preclinical studies.
Given the relevance of inflammatory reaction, anticytokines therapy, in particular the inhibition of interleukin 1 (IL-1), seems to be the most promising strategy. At the present time, intra-articular injection of IL-1 receptor antagonist is the only anticytokine approach that has been used in a human study of PTA. Despite the fact that knowledge in this area has increased in the past years, the identification of more specific disease markers and new therapeutic opportunities are needed.
Most destructive symptoms associated with arthritis and progressive back pain are due to chronic 'Autoimmune' inflammation
Hyperbaric Oxygen Tier 2, Targets Chronic Inflammation And Chronic Pain Syndromes
HBO at 1.75-2.4 ATA stimulates the patient’s own circulating stem cells (Abstract: 8-fold increase after 40- hours using 100% O2 at 2.0 ATA) and a range of growth factors including vascular endothelial and nerve growth factors critical for recovery.
* The positive clinical effects of Hyperbaric Oxygenation in the treatment of chronic inflammation is due to the effects on local and systemic Inflammatory Cytokines - IL-1, IL-6, IL17 and Tumor Necrosis Factor-alpha (TNF-alpha).
** Hyperbaric Oxygenation causes down regulation of inflammatory cytokines and the upregulation of Growth Factors required for stabilization and repair. HBO suppresses stimulus-induced proinflammatory cytokine production reducing the release of Tumor Necrosis Factor -alpha (TNF-a) and Endothelins.
HBO upregulates IL-10 - immune response anti-inflammatory which down-regulates pro-inflammatory species IL-1β, IL-2, IL-6 (Interleukin 6 can increase up to a 1,000-fold during trauma and infection), tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. Pro-apoptotic factors cytochrome c, caspase 3, and Bax are down-regulated by IL-10, whereas anti-apoptotic factors Bcl-2 and Bcl-xl are up-regulated by IL-10. IL-10 also provides trophic support to neurons through the IL-10 receptor. Increased tissue sparing, functional recovery, and neuroprotection are seen with an immediate post systemic administration of IL-10.
Stem Cell Mobilization and Vascular Endothelial Growth Factor (VEGF) levels are significantly increased with HBO therapy (100% O2 @ 1.8-2.0 ATA); whereas levels of prostaglandin E2 and cyclo-oxygenase-2 mRNA are markedly reduced. Therefore, the anti-inflammatory and immunosuppressive properties of Hyperbaric Oxygenation might account for its efficacy in the treatment and management of Immunosuppressive and Inflammatory conditions
HBO effects on Neuropathic Pain - TNF, IL6.pdf - Hyperbaric Oxygenation Therapy Alleviates Chronic Constrictive Injury–Induced Neuropathic Pain and Reduces Tumor Necrosis Factor-Alpha Production
Summary Effects HBO
* Hyperbaric Oxygen (HBO) UP~REGULATES Circulating Stem Cells (CD34+), Growth Factors (VEGF, BDNF, GDNF), Anti-inflammatory Interleukins including IL4, IL10, IL12, IL13 and INFγ (positive feedback loop).
** HBO DOWN~REGULATES Pro-inflammatory Interleukins IL1, IL2, IL6, IL7, IL8 and TNFα.
What Is The Underlying Cause Of Back Pain?
Managing Low Back Pain (3rd Edition); William H. Kirkaldy-Willis, MA, MD, LLD (Hon), FRCS (E and C), FACS, FICC (Hon), Emeritus Professor and Head, Department of Orthopaedic Surgery, University of Saskatchewan College of Medicine; Royal University Hospital, Saskatoon, Saskatchewan, Canada;
Kirkaldy-Willis details the ischemic model of back pain describing the 'degenerative cascade' associated with degenerative disc disease. ‘Structures within the spine have a very poor and often inadequate blood supply. There is minimal blood supply to the disc, and blood is what brings healing nutrients and Oxygen to damaged structures in the body. This means that the spinal disc lacks any significant reparative powers. Unlike muscles, which have good blood supply, once a spinal disc is injured it cannot repair itself.’
M. Adams, P Roughley Spine 2006 Lippincott Willams & Wilkins
'In adult discs, blood vessels are normally restricted to the outmost layers of the annulus. Metabolite transport is by diffusion, which is important for small molecules, and by bulk fluid flow, which is important for large molecules. Low oxygen tension in the center of a disc leads to anaerobic metabolism, resulting in a high concentration of lactic acid and low pH. In vitro experiments show that a chronic lack of oxygen causes nucleus cells to become quiescent, whereas a chronic lack of glucose can kill them. Deficiencies in metabolite transport appear to limit both the density and metabolic activity of disc cells. As a result, discs have only a limited ability to recover from any metabolic or mechanical injury. Endplate permeability and, therefore, disc metabolite transport normally decrease during growth and aging, and yet increase in the presence of disc degeneration and following endplate damage. This is one essential difference between aging and degeneration.'
What About Stem Cells - Inflammatory Cytokines block differentiation
Curr Stem Cell Res Ther. 2015 Feb 11. [Epub ahead of print]
1McGill University Health Centre, Department of Surgery, Montreal General Hospital, Room C9.173, 1650 Cedar Ave, Montreal, QC H3G 1A4. firstname.lastname@example.org.
Intervertebral disc degeneration is directly linked to chronic low back pain, a condition that affects multitudes of people worldwide and presents tremendous direct and indirect health costs. Water-loss, inflammation and disruption of the extracellular matrix ultimately result in loss of tissue function and associated pain. Cytokines present in degenerate tissue can upregulate protease activity and directly causes pain. Non-invasive therapies provide limited efficacy for pain management, and surgical intervention is therefore often required to treat chronic low back pain.
Disc removal can offer immediate pain-relief, however degeneration of adjacent segments can occur and pain can return. To circumvent the caveats of recurring pain and invasive surgeries, stem cell therapy is currently being investigated as a promising means to repair degenerating discs. However, while initial studies have shown promise, few studies have addressed whether stem cell therapies can modulate the inflammatory microenvironment or whether cytokines can affect the ability of the implanted cells to repair damaged tissue. This review focuses briefly on mechanisms of disc degeneration, with more attention given to the role of an inflammatory milieu in this process.
Cytokine upregulation in disc degeneration, the potential role of toll-like receptor signaling, and effects of these inflammatory factors on stem cells will be discussed. We find that while stem cell differentiation can be negatively influenced by inflammatory cytokines, stem cells can potentially have anti-inflammatory effects.
We conclude that further investigation of stem cell interactions with the inflammatory microenvironment is required, and that priming of stem cells under various conditions may be necessary for optimal therapeutic value for intervertebral disc repair and pain reduction.
Pain improvement in rheumatoid arthritis with hyperbaric oxygen: report of three cases.
Undersea Hyperb Med 2016 Jul-Aug;43(4):467-472
David Grant Medical Center (DGMC), 101 Bodin Circle, Travis Air Force Base, CA U.S.
Rheumatoid arthritis (RA) is a chronic, erosive, symmetrical inflammatory disease that can progress to synovial destruction, severe disability and premature mortality. Immunotherapies, while beneficial, can cause significant adverse events. Three patients with RA treated in our facility with hyperbaric oxygen (HBO₂) for unrelated diagnoses all reported significant but unanticipated improvement in RA-related pain, increased activity and improved sleeping patterns. Two improved while continuing traditional RA medications; the other patient had all RA meds held due to cancer and postoperative wound healing problems.
The significant symptomatic improvement in these three patients led us to hypothesize that HBO₂ for patients with RA may result in decreased joint pain, increased activity level, improvement in sleeping patterns and possibly a decreased need for standard rheumatologic medications, effectively reducing or avoiding the effects of immunosuppression. A clinical trial is planned to objectively assess these findings.
BMC Neurol. 2017 Dec 16;17(1):220. doi: 10.1186/s12883-017-1004-1.
Neuroprotective effects of hyperbaric oxygen (HBO) therapy on neuronal death induced by sciatic nerve transection in rat.
Recent studies shows that hyperbaric oxygen (HBO) therapy exerts some protective effects against neural injuries. The purpose of this study was to determine the neuroprotective effects of HBO following sciatic nerve transection (SNT).
Rats were randomly divided into five groups (n = 14 per group): Sham-operated (SH) group, SH + HBO group, SNT group, and SNT + pre- and SNT + post-HBO groups (100% oxygen at 2.0 atm absolute, 60 min/day for five consecutive days beginning on 1 day before and immediately after nerve transaction, respectively). Spinal cord segments of the sciatic nerve and related dorsal root ganglions (DRGs) were removed 4 weeks after nerve transection for biochemical assessment of malodialdehyde (MDA) levels in spinal cord, biochemical assessment of superoxide dismutase (SOD) and catalse (CAT) activities in spinal cord, immunohistochemistry of caspase-3, cyclooxigenase-2 (COX-2), S100beta (S100ß), and terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) in spinal cord and DRG.
The results revealed that MDA levels were significantly decreased in the SNT + pre-HBO group, while SOD and CAT activities were significantly increased in SNT + pre- and SNT + post-HBO treated rats. Attenuated caspase-3 and COX-2 expression, and TUNEL reaction could be significantly detected in the HBO-treated rats after nerve transection. Also, HBO significantly increased S100ß expression.
Based on these results, we can conclude that pre- and post-HBO therapy had neuroprotective effects against sciatic nerve transection-induced degeneration.
Spine J. 2016 Aug 4. pii: S1529-9430(16)30847-6. doi: 10.1016/j.spinee.2016.08.006. [Epub ahead of print]
Are modic changes associated with intervertebral disc cytokine profiles?
OF BACKGROUND DATA:
Degenerative changes including Modic Changes (MCs) are commonly observed in patients with chronic low back pain. Although intervertebral disc (IVD) cytokine expression has been shown to be associated with low back pain, the cytokine profile for degenerative IVD with and without MC has not been compared.
To evaluate the potential association between intervertebral disc cytokine expression and MCs.
Laboratory Study METHODS: The IVD from ten patients with Type II MCs and ten patients without MCs who underwent an anterior lumbar interbody and fusion for significant low back pain were collected. The expression levels of 42 cytokines were determined using a RayBio Human Antibody Array C3 and the results were verified with Enzyme-Linked Immunosorbent Assay (ELISA).
The cytokine array demonstrated a statistically significant increase in the expression of granulocyte-macrophage colony-stimulating factor (GM-CSF) (p = 0.001) and ENA-78 (p = 0.04), and a trend towards an increase in interleukin-1β (IL-1β) (p = 0.12) and tumor necrosis factor-α (TNF-α) (p = 0.22) in IVDs associated with Type II MCs. These results were validated with ELISA which demonstrated a 3.85 fold increase in theGM-CSF level between IVDs with Type II MCs compared to those without MCs (p = 0.03). Similarly there was a significant increase in the level of both ENA-78 (3.68 fold, p = 0.02) and IL-1β (2.11 fold, p = 0.01) in IVDs with Type II MCs. Lastly, there was a trend (p = 0.07) towards an increase in TNF-α in IVDs with Type II MCs (4.4 fold).
Intervertebral discs with Type II MCs demonstrate a significant increase in IL-1β, GM-CSF and ENA-78, and there is a trend towards an increase in TNF-α. These results further strengthen the association between MCs and low back pain.
Int J Clin Exp Med 2015 Jun 15;8(6):9979-84. eCollection 2015.
1Department of Traumatic Surgery, The Weifang People's Hospital Weifang 261041, China.
2Department of Orthopedics, The Binhai Development Zone People's Hospital Weifang 262737, China.
To compare the long and short term effectiveness of different preoperative approaches for lumber spinal fractures and finds a better surgical method for the disease. Follow up records of 144 patients received hyperbaric oxygen therapy or methylprednisolone infusion within 8 hours after the lubmer spinal injury were analyzed. Postoperative outcome immediately and 3, 6, 12, 36 months after the surgery were compared to evaluate the effectiveness two different approaches. The results indicated that there are no significant differences regarding age, sexual proportion, body mass index (BMI), visual analogue scale of pain (VAS) score as well as Frankel scores before the surgery, and significant differences VAS score as well as Frankel scores immediately after the surgery.
In conclusion, hyperbaric oxygen therapy within 8 hours after the injury can be more effective than methylprednisolone infusion in patients with lumber spinal injury.
Brain Behav Immun. 2015 Jan 31. pii: S0889-1591(15)00010-0. doi: 10.1016/j.bbi.2015.01.008. [Epub ahead of print]
1Communication and Research Unit for Musculoskeletal Disorders (FORMI), Oslo University Hospital, Norway. Electronic address: email@example.com.
2Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Norway. Electronic address: firstname.lastname@example.org.
3Communication and Research Unit for Musculoskeletal Disorders (FORMI), Oslo University Hospital, Norway. Electronic address: email@example.com.
4Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Norway; Faculty of medicine, University of Oslo, Norway. Electronic address: Ceroee@ous-hf.no.
5Department of Physical Medicine and Rehabilitation, Oslo University Hospital, Norway; National Institute of Occupational Health, Oslo, Norway; Department of Bioscience, University of Oslo, Norway. Electronic address: firstname.lastname@example.org.
Earlier studies indicate that lumbar radicular pain after disc herniation may be associated with a local inflammation induced by leakage of nucleus pulposus (NP) into the spinal canal and neuroforamen. In the present study we addressed the role of two interleukins, IL-6 and IL-8 in such long-lasting lumbar radicular pain. All 127 patients were recruited from Oslo University Hospital, Ullevål, Norway. At inclusion, 6weeks and 12months, serum concentrations of IL-6 and IL-8 were analyzed by enzyme-linked immunosorbent assay (ELISA) and pain intensity was reported on a 0-10cm visual analog scale (VAS). Significantly higher levels of IL-6 and IL-8 in serum were found in patients with VAS ⩾3 at 12months, than in patient with VAS <3 at 12months (p⩽0.01, test of between-subjects effect, repeated measures ANOVA, covariates for IL-6: age, smoking; covariates for IL-8: smoking, treatment).
For the first time we show that chronic lumbar radicular pain may be associated with a persistent increase of the pro-inflammatory substances IL-6 and IL-8 in serum after disc herniation.
Pain. 2015 Jan 27. [Epub ahead of print]
Peripheral interleukin-4 ameliorates inflammatory macrophage-dependent neuropathic pain
1aDepartment of Pharmacology, Wakayama Medical University, 811-1 Kimiidera, Wakayama 641-0012, Japan bDepartment of Pharmacology, Niigata University of Pharmacy and Applied Life Sciences, 265-1 Higashijima, Niigata 956-8603, Japan.
There is increasing evidence that inflammatory (M1-polarized) macrophages drive the nonresolving neuroinflammation that causes neuropathic pain after nerve injury. As interleukin-4 (IL-4) promotes the suppressive (M2-polarized) state in macrophages, we examined whether exploiting an IL-4-mediated pathway could ameliorate M1 macrophage-dependent neuropathic pain. The mRNA and protein expression of IL-4 receptor α chain (IL-4Rα) were upregulated in accumulating F4/80 macrophages in injured sciatic nerve (SCN). In mouse macrophage cell line J774A.1, IL-4 downregulated the mRNA expression of M1 macrophage-specific molecules (IL-1β, CC-chemokine ligand 3 and CD86) normally provoked by lipopolysaccharide, while increasing the mRNA expression of M2 macrophage-specific molecules (arginase-1, IL-10 and CD206) via a STAT6-mediated pathway. In ex vivo SCN culture, M1 molecules were highly expressed in the injured SCN on day 7 after partial SCN ligation (PSL), but were decreased by IL-4 treatment. In contrast, M2 molecules were upregulated by IL-4. IL-4 also increased phosphorylated STAT6 (pSTAT6) expression, and shifted IL-1β M1 macrophages toward a CD206 M2 phenotype. Perineural administration of IL-4 in mice subject to PSL ameliorated development and maintenance of tactile allodynia and thermal hyperalgesia. These effects of IL-4 were based on that IL-4 treatment increased the proportions of pSTAT6 and CD206 macrophages in injured SCN on day 14 after PSL.
We found that neuropathic pain can be ameliorated by IL-4 treatment, which exerts its therapeutic effect on accumulating macrophages via a STAT6-dependent pathway. A shift in macrophage phenotype from the inflammatory to the suppressive phenotype-driven by IL-4R signaling-may have benefits in the treatment of neuropathic pain.
BMC Musculoskelet Disord. 2014 Feb 25;15:56. doi: 10.1186/1471-2474-15-56.
Effects of hyperbaric oxygen on the osteogenic differentiation of mesenchymal stem cells
1Department of Physiology, College of medicine, Chang Gung University, 259 Wen-Hwa 1st Road, Kweishan, 333 Taoyuan, Taiwan. email@example.com.
Hyperbaric oxygenation was shown to increase bone healing in a rabbit model. However, little is known about the regulatory factors and molecular mechanism involved. We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is mediated via increases in the osteogenic differentiation of mesenchymal stem cells (MSCs) which are regulated by Wnt signaling.
The phenotypic characterization of the MSCs was analyzed by flow cytometric analysis. To investigate the effects of HBO on Wnt signaling and osteogenic differentiation of MSCs, mRNA and protein levels of Wnt3a, beta-catenin, GSK-3beta, Runx 2, as well as alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining were analyzed after HBO treatment. To investigate the effects of HBO on Wnt processing and secretion, the expression of Wntless and vacuolar ATPases were quantified after HBO treatment.
Cells expressed MSC markers such as CD105, CD146, and STRO-1. The mRNA and protein levels of Wnt3a, β-catenin, and Runx 2 were up-regulated, while GSK-3β was down-regulated after HBO treatment. Western blot analysis showed an increased β-catenin translocation with a subsequent stimulation of the expression of target genes after HBO treatment. The above observation was confirmed by small interfering (si)RNA treatment. HBO significantly increased alkaline phosphatase activity, calcium deposition, and the intensity of von Kossa staining of osteogenically differentiated MSCs. We further showed that HBO treatment increased the expression of Wntless, a retromer trafficking protein, and vacuolar ATPases to stimulate Wnt processing and secretion, and the effect was confirmed by siRNA treatment.
HBO treatment increased osteogenic differentiation of MSCs via regulating Wnt processing, secretion, and signaling.
Stem Cell Res. 2014 Jan;12(1):260-74. doi: 10.1016/j.scr.2013.10.007. Epub 2013 Nov 1.
Hyperbaric oxygen promotes osteogenic differentiation of bone marrow stromal cells by regulating Wnt3a/β-catenin signaling--an in vitro and in vivo study
1Institute of Biomedical Sciences, Chang Gung University, Taoyuan, Taiwan; Department of Orthopaedics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
2Department of Orthopaedics, Chang Gung Memorial Hospital, Taoyuan, Taiwan.
3Department of Orthopaedics, Chang Gung Memorial Hospital, Chiayi, Taiwan.
4Department of Physiology, Chang Gung University, Taoyuan, Taiwan. Electronic address: firstname.lastname@example.org.
We hypothesized that the effect of hyperbaric oxygen (HBO) on bone formation is increased via osteogenic differentiation of bone marrow stromal cells (BMSCs), which is regulated by Wnt3a/β-catenin signaling. Our in vitro data showed that HBO increased cell proliferation, Wnt3a production, LRP6 phosphorylation, and cyclin D1 expression in osteogenically differentiated BMSCs. The mRNA and protein levels of Wnt3a, β-catenin, and Runx2 were upregulated while those of GSK-3β were downregulated after HBO treatment. The relative density ratio (phospho-protein/protein) of Akt and GSK-3β was both up-regulated while that of β-catenin was down-regulated after HBO treatment. We next investigated whether HBO affects the accumulation of β-catenin. Our Western blot analysis showed increased levels of translocated β-catenin that stimulated the expression of target genes after HBO treatment. HBO increased TCF-dependent transcription, Runx2 promoter/Luc gene activity, and the expression of osteogenic markers of BMSCs, such as alkaline phosphatase activity, type I collagen, osteocalcin, calcium, and the intensity of Alizarin Red staining. HBO dose dependently increased the bone morphogenetic protein (BMP2) and osterix production. We further demonstrated that HBO increased the expression of vacuolar-ATPases, which stimulated Wnt3a secretion from BMSCs.
Finally, we showed that the beneficial effects of HBO on bone formation were related to Wnt3a/β-catenin signaling in a rabbit model by histology, mechanical testing, and immunohistochemical assays. Accordingly, we concluded that HBO increased the osteogenic differentiation of BMSCs by regulating Wnt3a secretion and signaling.
Eur Spine J. 2013 Apr;22(4):697-707. doi: 10.1007/s00586-013-2675-y. Epub 2013 Feb 13.
Antibiotic treatment in patients with chronic low back pain and vertebral bone edema (Modic type 1 changes): a double-blind randomized clinical controlled trial of efficacy.
1Research Department, Spine Centre of Southern Denmark, Institute of Regional Health Services Research, Lillebaelt Hospital, University of Southern Denmark, Middelfart, Denmark.
Modic type 1 changes/bone edema in the vertebrae are present in 6 % of the general population and 35-40 % of the low back pain population. It is strongly associated with low back pain. The aim was to test the efficacy of antibiotic treatment in patients with chronic low back pain (>6 months) and Modic type 1 changes (bone edema).
The study was a double-blind RCT with 162 patients whose only known illness was chronic LBP of greater than 6 months duration occurring after a previous disc herniation and who also had bone edema demonstrated as Modic type 1 changes in the vertebrae adjacent to the previous herniation. Patients were randomized to either 100 days of antibiotic treatment (Bioclavid) or placebo and were blindly evaluated at baseline, end of treatment and at 1-year follow-up.
Primary outcome, disease-specific disability, lumbar pain. Secondary outcome leg pain, number of hours with pain last 4 weeks, global perceived health, EQ-5D thermometer, days with sick leave, bothersomeness, constant pain, magnetic resonance image (MRI).
144 of the 162 original patients were evaluated at 1-year follow-up. The two groups were similar at baseline. The antibiotic group improved highly statistically significantly on all outcome measures and improvement continued from 100 days follow-up until 1-year follow-up. At baseline, 100 days follow-up, 1-year follow-up the disease-specific disability-RMDQ changed: antibiotic 15, 11, 5.7; placebo 15, 14, 14. Leg pain: antibiotics 5.3, 3.0, 1.4; placebo 4.0, 4.3, 4.3. Lumbar pain: antibiotics 6.7, 5.0, 3.7; placebo 6.3, 6.3, 6.3. For the outcome measures, where a clinically important effect size was defined, improvements exceeded the thresholds, and a trend towards a dose-response relationship with double dose antibiotics being more efficacious.
The antibiotic protocol in this study was significantly more effective for this group of patients (CLBP associated with Modic I) than placebo in all the primary and secondary outcomes.
Anesth Analg. 2011 Sep;113(3):626-33. doi: 10.1213/ANE.0b013e31821f9544. Epub 2011 May 19.
Hyperbaric oxygenation therapy alleviates chronic constrictive injury-induced neuropathic pain and reduces tumor necrosis factor-alpha production
Department of Anesthesiology, Upstate Medical University, 750 East Adams St., Syracuse, NY 13210, USA.
The development of hyperalgesia and allodynia after chronic constrictive injury (CCI) is associated with significantly increased tumor necrosis factor (TNF)-α and interleukin (IL)-1β. Theoretically, if the production of TNF-α and/or IL-1β could be reduced, neuropathic pain syndrome may be alleviated. Recently, a beneficial effect of hyperbaric oxygenation therapy (HBOT) in the treatment of pain disorders has been suggested. Our present study was designed to examine the hypotheses that (1) CCI-induced neuropathic pain may be associated with increased production of TNF-α and IL-1β, (2) HBOT may alleviate CCI-induced neuropathic pain, and (3) the alleviated neuropathic pain may be associated with reduced production of TNF-α and/or IL-1β.
Male rats (weighing 250-300 g) were anesthetized with ketamine and xylazine. The common sciatic nerve was exposed through the biceps femoris. Proximal to the sciatic's trifurcation, 4 ligatures were loosely tied around the nerve. In the sham group, an identical dissection was performed without ligation of the sciatic nerve. Mechanical allodynia and cold allodynia were tested by von Frey filament stimulation and the spread of acetone, respectively. HBO rats (n =18) were exposed to pure oxygen for 1 hour at 2.4 atm once a day. Non-HBO (n =18) and sham rats (n =6) were placed in the HBOT chamber breathing air. TNF-α and IL-1β in the sciatic nerve were assayed with ELISA. The presence of TNF-α protein in homogenates was verified by Western blot analysis.
CCI induced significant cold and mechanical allodynia as measured after CCI on days 4 and 7. The cold allodynia response frequency was significantly lower in HBO rats than in non-HBO rats. The values were 20% ± 1.6% vs 50% ± 4.5% on day 4 and 40% ± 4.6% vs 70% ± 4.5% on day 7 (F =87.42, confidence interval [for the difference between HBO and non-HBO]=29.612 ± 8.781, P < 0.05 for day 4 and day 7). The threshold of mechanical allodynia significantly increased in HBO rats compared with non-HBO rats. The values were 6.20 ± 0.9 vs 4.1 ± 1.0 g on day 4 and 3.8.2 ± 0.5 vs 2.3 ± 0.4 g on day 7 (F =18.8, confidence interval [for the difference between HBO and non-HBO]=1.806 ± 1.171, P < 0.05 for day 4 and day 7). TNF-α content was significantly higher in non-HBO rats than in sham rats on day 4 (17.89 ± 0.83 vs 10.66 ± 1.1 pg/mg protein, P < 0.05) and day 7 (18.97 ± 1.57 vs 9.09 ± 1.5 pg/mg protein, P < 0.05). HBOT significantly reduced TNF-α content to near the level in sham rats, which was 10.94 ± 2.78 and 11.32 ± 2.98 pg/mg protein on day 4 (P < 0.05 versus non-HBO) and 7 (P < 0.05 versus non-HBO), respectively. Western blot analysis confirmed the presence of proteins with molecular weights of 51 kDa in the rat sciatic nerve homogenates. IL-1β content was also significantly higher in non-HBO rats than in sham rats on day 4 (636 ± 74 vs 256 ± 31 pg/mg protein, P < 0.05) and on day 7 (687 ± 89 vs 288 ± 35 pg/mg protein, P < 0.05). HBOT had no effect on IL-1β content, which was 671 ± 85 pg/mg protein on day 4 and 672 ± 75 pg/mg protein on day 7 in HBO rats (P =not significant versus non-HBO rats).
These data show that HBOT alleviates CCI-induced neuropathic pain and inhibits endoneuronal TNF-α production, but not IL-1β in CCI-induced neuropathic pain. Reduced TNF-α production may, at least in part, contribute to the beneficial effect of HBOT.
J Neurotrauma 2013 Jun 3. [Epub ahead of print]
University of Wisconsin , Neurological Surgery, 600 Highland Avenue, Madison, Wisconsin, United States, 53792, 608-265-8800 ; email@example.com.
Spinal cord injury (SCI) is a devastating condition affecting 270,000 people in the United States. A potential treatment for decreasing the secondary inflammation, excitotoxic damage, and neuronal apoptosis associated with SCI is the anti-inflammatory cytokine interleukin-10.
The best characterized effects of
IL-10 are anti-inflammatory-it down-regulates pro-inflammatory species IL-1β, IL-2, IL-6, tumor necrosis factor-α, interferon-γ, matrix metalloproteinase-9, nitric oxide synthase, myeloperoxidase, and reactive oxygen species. Pro-apoptotic factors cytochrome c, caspase 3, and Bax are down-regulated by IL-10, whereas anti-apoptotic factors Bcl-2 and Bcl-xl are up-regulated by IL-10. IL-10 also provides trophic support to neurons through the IL-10 receptor.
Increased tissue sparing, functional recovery, and neuroprotection are seen with an immediate post-SCI systemic administration of IL-10. Treatment of SCI with IL-10 has been used successfully in combination with Schwann cell and olfactory glial cell grafts as well as methylprednisolone.
Minocycline, tetramethylpyrazine, and hyperbaric oxygen treatment all increase IL-10 levels in a SCI models and result in increased tissue sparing and functional recovery. A chronic systemic administration of IL-10 does not appear to be beneficial to SCI recovery and causes increased susceptibility to septicemia, pneumonia, and peripheral neuropathy. However, a localized up-regulation of IL-10 has been shown to be beneficial and can be achieved by herpes simplex virus gene therapy, injection of poliovirus replicons, or surgical placement of a slow-release compound. IL-10 shows promise as a treatment for SCI, although research on local IL-10 delivery timeline and dosage needs to be expanded upon.
J Pain. 2013 May 14. pii: S1526-5900(13)00839-0. doi: 10.1016/j.jpain.2013.02.003. [Epub ahead of print]
Repetitive Hyperbaric Oxygen Treatment Attenuates Complete Freund's Adjuvant-Induced Pain and Reduces Glia-Mediated Neuroinflammation in the Spinal Cord
Institute of Nautical Medicine, Jiangsu Key laboratory of Neuroregeneration, Nantong University, Nantong, China.
Hyperbaric oxygen (HBO) therapy is reported to attenuate pain in both clinical pain conditions and animal pain models, but the underlying mechanism remains to be investigated. Here, we show that 7 daily 60-minute HBO (100% oxygen, 2 atmosphere absolute) treatments effectively and persistently inhibited heat hyperalgesia, mechanical allodynia, and paw edema induced by peripheral injection of complete Freund's adjuvant (CFA). Five daily 60-minute HBO treatments also produced a prolonged reversal effect of the ongoing inflammatory pain.
Furthermore, such an HBO treatment reduced CFA-induced activation of glial cells, phosphorylation of mitogen-activated protein kinases, and production of a variety of proinflammatory cytokines (tumor necrosis factor alpha [TNF-α], interleukin-1 beta [IL-1β], and interleukin-6 [IL-6]) and chemokines (monocyte chemoattractant protein-1 [MCP-1], keratinocyte-derived chemokine [KC], and IFN-gamma-inducible protein 10 [IP-10]) in the spinal cord. HBO treatment also decreased lipopolysaccharide-induced mRNA expression of these cytokines and chemokines in primary cultures of astrocytes and microglia.
In addition, the mRNA expressions of IL-1β, IL-6, MCP-1, KC, and IP-10 in the inflamed paw skin were decreased by HBO. Taken together, these data suggest that HBO treatment is an effective therapy for inflammatory pain in animals. The inhibition of the neuroinflammation that is mediated by glial cells and inflammatory mediators may, at least in part, contribute to the antinociceptive effect of HBO therapy.
PERSPECTIVE: Our results suggest that repetitive HBO treatment attenuates CFA-induced pain and reduces glial activation and inflammatory mediators' production. These findings provide the evidence of the antinociception effect of HBO on inflammatory pain and characterize some of the underlying mechanisms.
Spinal Cord. 2012 Jul;50(7):502-6. doi: 10.1038/sc.2012.16. Epub 2012 Mar 6.
Evaluation of the effects of hyperbaric oxygen therapy for spinal cord lesion in correlation with the moment of intervention
Department of Orthopaedics and Traumatology, Hospital das Clínicas, Faculdade de Medicina da Universidade de São Paulo, São Paulo, Brazil.
Experimental, controlled, animal study.
To evaluate the functional effect of hyperbaric oxygen therapy administered shortly, one day after, and no intervention (control) in standardized experimental spinal cord lesions in Wistar rats.
In all, 30 Wistar rats with spinal cord lesions were divided into three groups: one group was submitted to hyperbaric oxygen therapy beginning half an hour after the lesion and with a total of 10 one-hour sessions, one session per day, at 2 atm; the second received the same treatment, but beginning on the day after the lesion; and the third received no treatment (control). The Basso, Beattie and Bresnahan scales were used for functional evaluation on the second day after the lesion and then weekly, until being killed 1 month later.
There were no significant differences between the groups in the functional analysis on the second day after the lesion. There was no functional difference comparing Groups 1 and 2 (treated shortly after or one day after) in any evaluation moment. On the 7th day, as well as on the 21st and 28th postoperative days, the evaluation showed that groups 1 and 2 performed significantly better than the control group (receiving no therapy).
Hyperbaric chamber therapy is beneficial in the functional recovery of spinal cord lesions in rats, if it is first administered just after spinal cord injury or within 24h.
J Neurotrauma. 2010 Jun;27(6):1121-7.
Attenuating experimental spinal cord injury by hyperbaric oxygen: stimulating production of vasculoendothelial and glial cell line-derived neurotrophic growth factors and interleukin-10
Graduate Institute of Clinical Medicine, Taipei Medical University, Taipei, Taiwan.
The present study was carried out to further examine the mechanisms underlying the beneficial effects of hyperbaric oxygen (HBO(2)) on experimental spinal cord injury (SCI). Rats were divided into three major groups: (1) sham operation (laminectomy only); (2) laminectomy + SCI + normobaric air (NBA; 21% oxygen at 1 ATA); and (3) laminectomy + SCI + HBO(2) (100% oxygen at 2.5 ATA for 2 h). Spinal cord injury was induced by compressing the spinal cord for 1 min with an aneurysm clip calibrated to a closing pressure of 55 g. HBO(2) therapy was begun immediately after SCI. Behavioral tests of hindlimb motor function as measured by the Basso, Beattie, and Bresnahan (BBB) locomotor scale was conducted on days 1-7 post-SCI. The triphenyltetrazolium chloride staining assay and terminal deoxynucleotidyl transferase-mediated deoxyuridine triphosphate biotin nick-end labeling assay were also conducted after SCI to evaluate spinal cord infarction and apoptosis, respectively. Cells positive for glial cell line-derived neurotrophic nerve growth factor (GDNF) and vascular endothelial growth factor (VEGF) and cytokines in the injured spinal cord were assayed by immunofluorescence and commercial kits, respectively.
It was found that HBO(2) therapy significantly attenuated SCI-induced hindlimb dysfunction, and spinal cord infarction and apoptosis, as well as overproduction of spinal cord interleukin-1beta and tumor necrosis factor-alpha.
In contrast, the numbers of both GDNF-positive and VEGF-positive cells and production of spinal cord interleukin-10 after SCI were all significantly increased by HBO(2). These data suggest that HBO(2) may attenuate experimental SCI by stimulating production of GDNF, VEGF, and interleukin-10.
Acta Orthop Belg. 2012 Oct;78(5):685-7.
There may be a role for hyperbaric oxygen therapy in transient osteoporosis of the hip
Department of Underwater and Hyperbaric Medicine, GATA Haydarpasa Teaching Hospital, 34668 Uskudar, Istanbul, Turkey.
Transient osteoporosis of the hip (TOH) is a rare clinical condition with usually an unknown aetiology and which typically develops in middle-aged men, or in women in the third trimester of their pregnancy. It is characterized by transient osteopenia and by gradually increasing pain associated with a limitation of the range of motion of the hip. Bone marrow oedema is a typical but nonspecific finding in TOH.
A 33-year-old female patient presented with severe hip pain one month after delivery. Her history was unremarkable except for a Hashimoto's Disease of 8 years' duration. Magnetic resonance imaging (MRI) showed significant bone marrow oedema with increased signal intensity in the femoral head on T2-weighted images.
A diagnosis of TOH was made and the patient received a total of 30 sessions of hyperbaric oxygen (HBO) at 2.4 ATA, 2 hours each, in a multiplace chamber. Over the course of HBO treatment, her pain was gradually relieved and she became asymptomatic after one month together with a complete recovery of the range of motion of the hip. MRI of the hips 10 weeks after onset of HBO therapy showed normal signal intensity on T2-weighted images.
J Orthop Res. 2011 Jan;29(1):14-9. doi: 10.1002/jor.21195.
Beneficial effects of hyperbaric oxygen on human degenerated intervertebral disk cells via suppression of IL-1β and p38 MAPK signal
Department of Orthopaedic Surgery and Hyperbaric Oxygen Therapy Center, Chang Gung Memorial Hospital, No 5, Fu-Hsing Street 333, Kweishan, Taoyuan, Taiwan.
Nucleus pulposus cells (NPCs) from degenerating disks produce catabolic and inflammatory factors, including interleukin (IL)-1, nitric oxide (NO), prostaglandin E2 (PGE-2), and matrix metalloproteinaes (MMPs). An imbalance between MMPs and tissue inhibitors of matrix metalloproteinases (TIMPs) has been proposed to exist in the degenerating disk.
This study evaluates the effects of hyperbaric oxygen (HBO) on the human degenerated NPCs. NPCs were maintained in alginate bead culture. All hyperoxic cells were exposed to 100% O(2) at 2.5 atmospheres absolute (ATA) in a hyperbaric chamber. p38 MAPK phosphorylation of the NPCs was detected using the phosphor-kinase array kit. RNA was isolated for real-time quantitative polymerase chain reaction (Q-PCR) analysis of aggrecan and type II collagen gene expression. The amounts of IL-1β, NO, PGE-2, MMP-3, and TIMP-1 in the conditioned media were quantified by enzyme-linked immunosorbent assay (ELISA).
Our data showed that HBO treatment decreased expression of IL-1β, increased the gene expression of aggrecan and type II collagen, suppressed the phosphorylation of p38 MAPK, decreased NO, PGE-2, and MMP-3, and increased TIMP-1 expression in NPCs as compared with the atmospheric treatment.
These results support the hypothesis that IL-1β and the p38 MAPK signal may be responsible for many of the inflammatory and catabolic changes seen in the human disk degeneration, and support our proposal that HBO treatment-induced increase of the anabolic factor (TIMP-1)/catabolic factor (MMP-3) ratio may provide a therapeutic approach to slow the course of intervertebral disk degeneration.
Effect of hyperbaric Oxygenation on intervertebral disc degeneration 2011
Study Design. An in vitro study with degenerated human lumbar intervertebral disc specimens cultured under hyperbaric Oxygenation (HBO). Objective. To observe the changes in interleukin (IL)-1β, prostaglandin (PG) E-2, nitric oxide (NO), cell growth, and apoptosis of the human nucleus pulpous cell (NPC) after HBO. Summary of Background Data. Intervertebral disc degeneration has been demonstrated to be related to IL-1β, PGE-2, NO, and O2 concentration but the actual mechanism is not clear. HBO also has also been reported in the literature to influence changes in IL-1β, PGE-2, NO, and O2 concentration. However, the direct effect of HBO on the disc cells has not been previously reported. Methods. We collected 12 human lumbar degenerated disc specimens and evaluated the effects of HBO on the cultured NPCs. The amounts of IL-1β, PG-E2, and NO in the conditioned medium were quantified by enzyme-linked immunosorbent assay (ELISA) and high performance liquid chromatography (HPLC). Cell growth was measured by increase in cell number. Cell viability and proteoglycan content were evaluated by histological study using safranin O staining. In situ analysis of apoptosis was performed using TUNEL staining.
Results. Our data indicated that HBO treatment inhibited IL-1β, PG-E2, and NO production but increased cell number and matrix synthesis of cultured NPCs. TUNEL staining showed that HBO treatment suppressed the apoptosis of cultured NPCs. Conclusion. HBO provides a potential treatment modality for disc degeneration.
J Orthop Res. 2012 Aug 6. doi: 10.1002/jor.22209. [Epub ahead of print]
Hyperbaric oxygen treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells
Department of Orthopaedic Surgery, Hyperbaric Oxygen Therapy Center, Chang Gung Memorial Hospital, Taoyuan, Taiwan; College of Medicine, Chang Gung University, Taoyuan, Taiwan.
Nucleus pulposus cells (NPCs) from degenerating discs produce catabolic and inflammatory factors, including interleukin (IL)-1 and nitric oxide (NO). Enhanced production of NO has been implicated in the apoptosis of degenerating disc cells. This study evaluates the effects of hyperbaric oxygen (HBO) on degenerated human NPCs. All hyperoxic cells were exposed to 100% O(2) at 2.5 atmospheres absolute (ATA). Phosphorylation of extracellular signal-regulated kinase 1/2 (ERK1/2), c-Jun N-terminal kinase (JNK), and p38 mitogen-activated protein kinase (MAPK) in NPCs was detected using the phosphor-kinase array kit. RNA was isolated for real-time polymerase chain reaction (PCR) analysis of aggrecan and type II collagen gene expression. The levels of IL-1β and NO were quantified by enzyme-linked immunosorbent assay (ELISA). To identify the HBO-induced anti-apoptotic pathways, expression of Bcl-2 and Bax proteins as well as activation of cysteine-containing aspartate-specific proteases (caspases) 3, 8, and 9 was evaluated using Western blotting after HBO treatment.
Our data showed that HBO treatment decreased the expression of IL-1β, suppressed phosphorylation of ERK1/2, JNK, and p38 MAPK, decreased synthesis of NO, and increased the gene expression of aggrecan and type II collagen in NPCs as compared with the atmospheric treatment. HBO up-regulated the ratio of Bcl-2 to Bax expression and reduced the activity of caspases 9 and 3 but not of caspase 8, indicating a selective effect over the mitochondrial apoptosis pathway in degenerated NPCs. These results support our hypothesis that HBO treatment suppresses MAPK signaling and mitochondrial apoptotic pathway in degenerated human intervertebral disc cells. © 2012 Orthopaedic Research Society. Published by Wiley Periodicals, Inc. J Orthop Res.
Undersea Hyperb Med. 2011 Sep-Oct;38(5):345-66.
Hyperbaric oxygen therapy and promoting neurological recovery following nerve trauma
Dept. of Hyperbaric Medicine, Medical Services Administration of Puerto Rico.
There is a constant search for new techniques that induce more extensive and rapid wound healing. Hyperbaric oxygen therapy (HBO2T) involves placing a patient in a sealed chamber and elevating its pressure several-fold above ambient air pressure while the patient breathes 100% oxygen. HBO2T induces a number of physiological actions, and which wounds are selected for HBO2T depends on the specific actions of HBO2T relative to the wound's healing requirements. Although nerve traumas are not yet indicated for HBO2T, there are many animal and clinical examples showing the benefits of HBO2T in inducing neurological recovery following nerve trauma. This review examines the general mechanisms required to induce wound healing and the actions of HBO2T which meet these requirements. It then examines the requirements for inducing axon regeneration and how many are met by HBO2T.
Finally, we discuss anecdotal evidence that HBOT enhances the rate and extent of axon regeneration in both animal models and clinically. We conclude that HBOT triggers most of the mechanisms required to induce axon regeneration.
Spine (Phila Pa 1976). 2012 Nov 7. [Epub ahead of print]
Effect of hyperbaric oxygenation on intervertebral disc degeneration: An in vivo study with Sprague-Dawley rats
Institution: Department of Orthopaedic Surgery and Hyperbaric Oxygen Therapy Center, Chang Gung Memorial Hospital at Keelung College of Medicine, Chang Gung University.
ABSTRACT: Study Design. An in vivo study was conducted to test the effect of hyperbaric oxygenation (HBO) on intervertebral disc degeneration in Sprague-Dawley (SD) rats. Objective. To observe the changes in intervertebral disc height, and levels of glycosaminoglycan (GAG), collagen, interleukin (IL-1β), prostaglandin (PGE-2), and inducible nitric oxide synthase (iNOs) in degenerated intervertebral discs after HBO treatment.
Summary of Background Data. Although the involvement of IL-1β, PGE-2, NO, and low O2 concentration has been demonstrated in intervertebral disc degeneration, the actual mechanism is not clear. It has been reported that HBO influences changes in IL-1β, PGE-2, NO, and O2 concentration. Previously, one study demonstrated an in vitro positive effect of HBO on the human nucleus pulposus. Thus, an in vivo study in animals was necessary.
Methods. Twelve SD rats were each injected with chondroitinase ABC in two proxim al intervertebral discs of the tail. After treating with 100% oxygen at 2.5 atmospheres 2 hours per days for 10 days, the change in disc height was determined by radiography. The amounts of PGE-2, iNOs, glycosaminoglycan (GAG), and total collagen in the intervertebral disc were quantified by enzyme-linked immunosorbent assay. Tissue morphology and the distributions of GAG, IL-1β, and iNOs in the intervertebral disc were assessed by histology and immunohistochemistry studies. The area of IL-1β in the intervertebral discs was quantified using image analysis software.
Results. HBO treatment stopped the decrease in intervertebral disc height, caused an increase in the amount of glycosaminoglycan, and inhibited IL-1β, PGE2, and iNOs production. Conclusion. HBO provides a potential treatment modality for intervertebral disc degeneration.
Effect of hyperbaric oxygenation on intervertebral disc degeneration: an in vitro study with human lumbar nucleus pulposus
Department of Orthopaedic Surgery and Hyperbaric Oxygen, Therapy Center, Chang Gung Memorial Hospital, College of Medicine, Chang Gung University, Kwei-Shan Tao-Yuan, Taiwan.
An in vitro study with degenerated human lumbar intervertebral disc specimens cultured under hyperbaric oxygenation (HBO).
To observe the changes in interleukin (IL)-1β, prostaglandin (PG)-E2, nitric oxide (NO), cell growth, and apoptosis of the human nucleus pulposus cell (NPC) after HBO.
SUMMARY OF BACKGROUND DATA
Intervertebral disc degeneration has been demonstrated as related to IL-1β, PG-E2, NO, and O2 concentration but the actual mechanism is not clear. HBO also has also been reported in the literature to influence changes in IL-1β, prostaglandin E2, NO, and O2 concentration. However, the direct effect of HBO on the disc cells has not been previously reported.
We collected 12 human lumbar degenerated disc specimens and evaluated the effects of HBO on the cultured NPCs. The amounts of IL-1β, PG-E2, and NO in the conditioned medium were quantified by enzyme-linked immunosorbent assay and high performance liquid chromatography. Cell growth was measured by increase in cell number. Cell viability and proteoglycan content were evaluated by histologic study using safranin O staining. In situ analysis of apoptosis was performed using Terminal deoxynucleotidyl transferase dUTP nick end labeling (TUNEL) staining.
Our data indicated that HBO treatment inhibited IL-1β, PG-E2, and NO production but increased cell number and matrix synthesis of cultured NPCs. TUNEL staining showed that HBO treatment suppressed the apoptosis of cultured NPCs.
HBO provides a potential treatment modality for disc degeneration.
Onesti ST (Neurologist. 2004 Sep;10(5):259-64)
Failed Back Syndrome (FBS) is a well-recognized complication of surgery of the lumbar spine. It can result in chronic pain and disability, often with disastrous emotional and financial consequences to the patient. Many patients have traditionally been classified as ‘spinal cripples’ and are consigned to a life of long-term narcotic treatment with little chance of recovery. The issue of chronic pain associated with failed spinal surgery was reported as far back as in 1994.
Outcome of lumbar fusion in Washington State workers' compensation (Franklin 1994), Spine.
Franklins et al. covered a large, population-based cohort of workers in the Washington State workers' compensation system who received lumbar fusion between August 1, 1986 and July 31, 1987 to determine work disability status, reoperation rate, and patient satisfaction.
Most patients reported that back pain (67.7%) was worse and overall quality of life (55.8%) was no better or worse than before surgery.
Conclusion: Outcome of lumbar fusion performed on injured workers was worse than reported in published case series. Prospective studies should be conducted to determine the biologic indications that might lead to improved outcomes in this disabled population.
SpineCare Medical Group, San Francisco Spine Institute, Daly City, California, USA.
Pain Med. 2002 Mar;3(1):18-22
BACKGROUND: Patients who do not improve after lumbar surgery may be given the nonspecific label of failed back surgery syndrome (FBSS). Since 1981, there has not been a quantitative assessment of the etiologies of FBSS despite major improvements in surgical techniques and diagnostic testing.
PURPOSE: To define the causes of FBSS seen in a referral-based spine center.
STUDY DESIGN AND METHODS: Retrospective review of 181 consecutive charts of patients seen at a single spine center because of continued pain after lumbar surgery performed elsewhere. Evaluation was individualized based on history and physical examination and included x-rays, CT scans, MRI, selective nerve root injections, discography, and psychiatric evaluation.
PATIENT SAMPLE: There were 101 men and 80 women; mean age was 47 years.
There were 118 patients with one prior surgery, 52 with two, 6 with three, and 5 with four. Mean interval from the last prior surgery to the first clinic visit was 33 months.
RESULTS: A predominant diagnosis could be established in 170 of 181 (94%) patients, included foraminal stenosis (29%), painful disc(s) (17%), pseudarthrosis (14%), neuropathic pain (9%), instability (5%), and psychological problems (3%).
CONCLUSION: We were able to establish a predominant diagnosis in 94% of our patients. Foraminal stenosis remains the leading cause of FBSS, but painful discs are also common. Recurrent disc herniation is seen less often than in the past, and there is increased recognition of neuropathic pain. Knowledge of the potential causes of FBSS leads to a more efficient and cost-effective evaluation of these patients.