Idiris Altun

Cytokine profile in degenerated painful intervertebral disc: variability with respect to duration of symptoms and type of disease

BACKGROUND CONTEXT Neuroinflammation is supposed to play a crucial role in the generation of chronic pain. Numerous trials have documented the contribution of proinflammatory cytokines in the pathophysiology of pain associated with peripheral and central nociception. Local and systemic expressions of proinflammatory cytokines have been implicated as mediators of pain. Among these cytokines, tumor necrosis factor-α (TNF-α), interleukin-1β (IL-1β), and interleukin-6 (IL-6) are especially notable because of their hyperalgesic impacts after nerve damage. PURPOSE The aim of the present study was to evaluate and compare the tissue levels of IL-1β, IL-6, interleukin-10 (IL-10), and TNF-α in subligamentous and free fragment types of degenerated intervertebral disc in acute and chronic periods. STUDY DESIGN This was a cross-sectional study. PATIENT SAMPLE A cross-sectional study was implemented on a total of 49 patients (24 women, 25 men) with an average age of 38.2±4.9 treated surgically by means of microdiscectomy. OUTCOME MEASURES Of these cases, 19 had complaints for less than 6 months, whereas 30 patients had been suffering from low back pain and leg pain for more than 6 months. Thirty-eight patients have been diagnosed with subligamentous type and 11 patients had free fragment type of disc degeneration. METHODS The levels of IL-1β, IL-6, IL-10, and TNF-α were assessed in tissue samples prepared from nucleus pulposus tissue obtained during microdiscectomy. Results were compared in patients with acute and chronic duration of complaints, as well as subligamentous and free fragment types of intervertebral disc degeneration. RESULTS The levels of IL-1β (p<.001), IL-6 (p<.001), IL-10 (p<.001), and TNF-α (p<.001) were significantly higher in patients with acute duration of complaints. Similarly, free fragment type of intervertebral disc degeneration displayed remarkably higher levels of IL-1β (p=.009), IL-6 (p<.001), IL-10 (p=.024), and TNF-α (p=.017) compared with the subligamentous type. CONCLUSIONS Inflammatory cytokines seem to have a more apparent role in intervertebral disc degeneration especially in acute period and in free fragment type. Further trials should be performed for elucidation of pathophysiology at the molecular level and the development of more effective diagnostic and therapeutic measures.

Vitamin B complex and vitamin B12 levels after peripheral nerve injury

The aim of the present study was to evaluate whether tissue levels of vitamin B complex and vitamin B 12 were altered after crush-induced peripheral nerve injury in an experimental rat model. A total of 80 male Wistar rats were randomized into one control (n = 8) and six study groups (1, 6, 12, 24 hours, 3, and 7 days after experimental nerve injury; n = 12 for each group). Crush-induced peripheral nerve injury was performed on the sciatic nerves of rats in six study groups. Tissue samples from the sites of peripheral nerve injury were obtained at 1, 6, 12, 24 hours, 3 and 7 days after experimental nerve injury. Enzyme-linked immunosorbent assay results showed that tissue levels of vitamin B complex and vitamin B 12 in the injured sciatic nerve were significantly greater at 1 and 12 hours after experimental nerve injury, while they were significantly lower at 7 days than in control group. Tissue level of vitamin B 12 in the injured sciatic nerve was significantly lower at 1, 6, 12 and 24 hours than in the control group. These results suggest that tissue levels of vitamin B complex and vitamin B 12 vary with progression of crush-induced peripheral nerve injury, and supplementation of these vitamins in the acute period may be beneficial for acceleration of nerve regeneration.

Modulation of cytokine levels in ameliorative effects of pulsed magnetic field on an experimental model of Chronic Constriction Injury

Abstract Purpose: Clinical chronic neuropathic pain is often resistant to currently used pharmacotherapeutic applications. A number studies have shown that pulsed magnetic field (PMF) application may ameliorate the pain associated with damages, surgeries or diseases. However, possible potential mechanisms of PMF treatments have not been well documented. This study aimed to assess the therapeutic effects of PMF treatment on a Chronic Constriction Injury model (CCI) which mimics clinical chronic neuropathic pain symptoms. Materials and methods: Effects of PMF treatments or sham PMF (SPMF) were investigated by measuring the latencies, thresholds and cytokine levels (interleukin [IL]-1 beta, IL-6 and IL-10) of sciatic nerve in CCI or sham surgery rats. PMF was treated on CCI rats before (a day after surgery, PMF-AD) and after (a week after surgery, PMF-AW) the development of pain signs. Results: Rats exhibited hyperalgesia and allodynia within one week following surgery, and lasted through the experiment. PMF treatments, but not SPMF, significantly enhanced the latency and threshold. Both anti-hyperalgesic and anti-allodynic actions of PMF-AD were greater than those of PMF-AW treatment. Similarly, PMF-AD had more pronounced effects on the level of pro- and anti-inflammatory cytokines than did PMF-AW. Conclusions: The present findings may suggest that PMF treatment may reverse the CCI-induced changes in neuropathic pain behaviors by decreasing the production of pro-inflammatory cytokines and increasing the anti-inflammatory cytokine production at the site of injury.

Pulsed magnetic field enhances therapeutic efficiency of mesenchymal stem cells in chronic neuropathic pain model

Cell-based or magnetic field therapies as alternative approaches to pain management have been tested in several experimental pain models. The aim of this study therefore was to investigate the actions of the cell-based therapy (adipose tissue derived mesenchymal stem cells; ADMSC) or pulsed magnetic field (PMF) therapy and magneto-cell therapy (combination of ADMSC and PMF) in chronic constriction nerve injury model (CCI). The actions of individual ADMSC (route dependent [systemic or local], time-dependent [a day or a week after surgery]), or PMF and their combination (magneto-cell) therapies on hyperalgesia and allodynia were investigated by using thermal plantar test and a dynamic plantar aesthesiometer, respectively. In addition, various cytokine levels (IL-1β, IL-6, and IL-10) of rat sciatic nerve after CCI were analyzed. Following the CCI, both latency and threshold significantly decreased. ADMSC or PMF significantly increased latencies and thresholds. The combination of ADMSC with PMF even more significantly increased latency and threshold when compared with ADMSC alone. However, ADMSC-induced decrease in pro-inflammatory or increase in anti-inflammatory cytokines levels were partially prevented by PMF treatments. Present findings may suggest that both cell-based and magnetic therapies can effectively attenuate chronic neuropathic pain symptoms. Combined magneto-cell therapy may also efficiently reverse neuropathic signs. Bioelectromagnetics. 38:255-264, 2017.

Ankylosing Spondylitis: Patterns of Spinal Injury and Treatment Outcomes

Study Design Retrospective review. Purpose We retrospectively reviewed our patients with ankylosing spondylitis (AS) to identify their patterns of spinal fractures to help clarify management strategies and the morbidity and mortality rates associated with this group of patients. Overview of Literature Because of the brittleness of bone and long autofused spinal segments in AS, spinal fractures are common even after minor trauma and often associated with overt instability. Methods Between January 1, 1998 and March 2011, 30 patients (23 males, 7 females; mean age, 70.43 years; range, 45 to 95 years) with the radiographic diagnosis of AS of the spinal column had 42 fractures. Eight patients presented with significant trauma, 17 after falls, and 5 after minor falls or no recorded trauma. Eleven patients presented with a neurological injury, ranging from mild sensory loss to quadriplegia. Results There were 16 compression and 10 transverse fractures, two Jeffersons fractures, one type II and two type III odontoid process fractures, and five fractures of the posterior spinal elements (including lamina and/or facet, three spinous process fractures, three transverse process fractures). Twenty-four fractures affected the craniocervical junction and/or cervical vertebrae, 17 were thoracic, and one involved the lumbar spine. The most affected vertebrae were C6 and T10. The mean follow-up was 29.9 months. One patient was lost to follow-up. Eighteen patients were treated conservatively with bed rest and bracing. Twelve patients underwent surgery for spinal stabilization either with an anterior, posterior or combined approach. Conclusions Nonsurgical treatment can be considered especially in the elderly patients with AS and spinal trauma but without instability or major neurological deficits. The nonfusion rate in conservatively treated patients is low. When treatment is selected for patients with spinal fractures and AS, the pattern of injury must be considered and the need for individualized treatment is paramount.

An Experimental Study on the Effects of Smoking in the Perinatal Period and During Lactation on the Intervertebral Disks of Newborns

OBJECTIVE To evaluate the histopathologic effects of smoking before, during, and after pregnancy on the intervertebral disk structure of newborns in an experimental rat model. METHODS Seven adult female Wistar albino rats were randomly allocated into 7 groups. Nicotine (2 mg/kg/d) was intraperitoneally introduced to these rats in 6 groups before, during, and after pregnancy, whereas the rat in the control group received isotonic saline intraperitoneally. Fourteen newborns delivered by each rat were euthanized at the end of 9 weeks after being breastfed for 3 weeks after birth. The vertebral columns of the euthanized rats were removed en bloc, and histopathologic evaluation was performed on the intervertebral disk specimens. Histopathologic alterations were noted and compared between groups. RESULTS Ratio of proteoglycan amount exhibited a significant difference between groups (P < 0.001). Subjects in the control group had a predominantly mild amount of proteoglycans, whereas smoking before and during pregnancy and smoking before/during pregnancy and lactation resulted in deposition of a severe amount of proteoglycans in intervertebral disk tissue. Similarly, there was a statistically significant difference between groups with respect to the amount of fibrosis (P < 0.001). In the control group, fibrosis was absent in most (78.6%) subjects. Fibrosis was mild in groups with smoking before pregnancy and during lactation. A moderate degree of fibrosis was detected in groups with smoking during pregnancy, before and during pregnancy, during pregnancy and lactation, and before/during pregnancy and lactation. CONCLUSIONS Results of this study imply that maternal smoking before and during pregnancy and in the lactation period may have deleterious effects on the intervertebral disk of the newborn. The duration of smoking and fertility period can influence the type and severity of these effects.

Lumbar herniated disc: spontaneous regression

Background Low back pain is a frequent condition that results in substantial disability and causes admission of patients to neurosurgery clinics. To evaluate and present the therapeutic outcomes in lumbar disc hernia (LDH) patients treated by means of a conservative approach, consisting of bed rest and medical therapy. Methods This retrospective cohort was carried out in the neurosurgery departments of hospitals in Kahramanmaraş city and 23 patients diagnosed with LDH at the levels of L3−L4, L4−L5 or L5−S1 were enrolled. Results The average age was 38.4 ± 8.0 and the chief complaint was low back pain and sciatica radiating to one or both lower extremities. Conservative treatment was administered. Neurological examination findings, durations of treatment and intervals until symptomatic recovery were recorded. Laségue tests and neurosensory examination revealed that mild neurological deficits existed in 16 of our patients. Previously, 5 patients had received physiotherapy and 7 patients had been on medical treatment. The number of patients with LDH at the level of L3−L4, L4−L5, and L5−S1 were 1, 13, and 9, respectively. All patients reported that they had benefit from medical treatment and bed rest, and radiologic improvement was observed simultaneously on MRI scans. The average duration until symptomatic recovery and/or regression of LDH symptoms was 13.6 ± 5.4 months (range: 5−22). Conclusions It should be kept in mind that lumbar disc hernias could regress with medical treatment and rest without surgery, and there should be an awareness that these patients could recover radiologically. This condition must be taken into account during decision making for surgical intervention in LDH patients devoid of indications for emergent surgery.

Impact of Position on Efficacy of Caudal Epidural Injection for Low Back Pain and Radicular Leg Pain Due to Central Spinal Stenosis and Lumbar Disc Hernia

Objective This study was performed to evaluate and compare the efficacies of caudal epidural injections performed at prone and lateral decubitus positions. Methods A total of 120 patients suffering from low back pain and radicular leg pain were included and patients were randomly distributed into 2 groups according to the position during injection. In Group 1 (n=60; 32 women, 28 men), caudal epidural injection was performed at prone position, whereas it was implemented at lateral decubitus position in Group 2 (n=60; 33 women, 27 men). Visual analogue scale, Oswestry Disability Index (ODI), walking tolerance (WT) and standing tolerance (ST) were compared in 2 groups before and after injection. Results In Group 1, ODI values were higher at 30th minute (p=0.007), 3rd week (p=0.043) and 6th month (p=0.013). In Group 1, ODI, VAS and ST values were improved significantly at all follow-up periods compared to initial values. In Group 1, WT scores were better than initial values at 30th minute, 3rd week and 3rd month. In Group 2, ODI scores at 30th minute, 3rd week, 3rd month and 6th month were improved while VAS and ST scores were improved at all periods after injection. WT scores were better at 30th minute, 3rd week and 3rd month compared to initial WT scores. Conclusion Our results indicated that application of injection procedure at lateral decubitus position allowing a more concentrated local distribution may provide better relief of pain.

Histopathological Analysis of Ligamentum Flavum in Lumbar Spinal Stenosis and Disc Herniation

Study Design Histopathological analyses were performed in ligamentum flavum (LF) hypertrophy patients with lumbar spinal stenosis (LSS) and lumbar disc herniation (LDH). Purpose The aim of the present study was to evaluate histopathological changes in LF patients with LSS and LDH. Overview of Literature LSS is the most common spinal disorder in elderly patients. This condition causes lower back and leg pain and paresis, and occurs as a result of degenerative changes in the lumbar spine, including bulging of the intervertebral discs, bony proliferation of the facet joints, and LF thickening; among these, LF thickening is considered a major contributor to the development of LSS. Methods A total of 71 patients operated with the surgical indications of LSS and LDH were included. LF samples were obtained from 31 patients who underwent decompressive laminectomy for symptomatic degenerative LSS (stenotic group) and from 40 patients who underwent lumbar discectomy for LDH (discectomy group). LF materials were examined histopathologically, and other specimens were examined for collagen content, elastic fiber number and array, and presence of calcification. Results The stenotic and discectomy groups did not differ with regard to mean collagen concentration or mean elastic fiber number (p=0.430 and p=0.457, respectively). Mean elastic fiber alignment was 2.36±0.99 in the stenotic group and 1.38±0.54 in the discectomy group (p<0.001). Mean calcification was 0.39±0.50 in the stenotic group, whereas calcification was not detected (0.00±0.00) in the discectomy group; a statistically significant difference was detected (p<0.001) between groups. Conclusions LF hypertrophy in spinal stenosis may occur as a result of elastic fiber misalignment along with the development of calcification over time. Further studies determining the pathogenesis of LSS are needed.

Anti-hypernociceptive and anti-oxidative effects of locally treated dobutamine in diabetic rats

BACKGROUND Oxidative stress as a significant factor in the development of diabetes induced neuropathic pain as well as the potential for prevention of this complication. Therefore, we hypothesized that locally administrated dobutamine, a beta-adrenoreceptor agonist, or esmolol, a beta-adrenoreceptor antagonist, can modulate the oxidative stress and ameliorate the diabetes induced neuropathic pain. METHODS Effects of locally (intraplantar) treated two pharmaceutical preparations used in clinical applications, dobutamine or esmolol, were investigated by measuring thermal latencies, mechanical thresholds and several oxidative stress parameters in streptozotocin (STZ) induced diabetic rats. RESULTS Diabetes induced hyperalgesia and allodynia more effectively relieved by dobutamine than esmolol. Anti-hypersensitive action of dobutamine continued through the experiment. Diabetes induced oxidative damage in the paw tissues since STZ rats showed significant increased malondialdehyde (MDA), nitric oxide (NO) and decreased superoxide dismutase (SOD), catalase (CAT), myeloperoxidase (MPO) in the paw. Dobutamine, but not esmolol, restored the tissue oxidative and nitrossive stress parameters to those observed in the non-diabetic rats. CONCLUSIONS Findings suggest that diabetes-induced oxidative stress may be partially responsible for the development of diabetic neural complications. Amelioration of oxidative stress by locally treated dobutamine can be beneficial in diabetes induced neuropathic pain.