Pulsed Magnetic Field Treatment for Calming Neuroinflammation in Pain Conditions.

Context: Neuroinflammation can be associated with inflammatory mediators, such as cytokines and chemokines, that follow damage, injury, infection, or illness in the peripheral nervous system (PNS) and/or the central nervous system (CNS). These can play strategic roles in the formation and continuation of abnormal pain behaviors. Pulsed magnetic field (PMF) treatments have attracted attention for the prevention and management of various pain conditions. Objective: The review intended to examine the mechanisms underlying the documented anti-neuroinflammatory effects of PMF treatment and its beneficial effects for neuroinflammatory pain states. Design: The research team performed a narrative review by searching for articles in the PubMed databases. The search used the keywords, pulsed magnetic field, neuroinflammation, cytokines, chemokines, pain, alone and in combination, without the restriction of the publication date. Setting: This study was take place in faculty of medicine, Usak University, Usak, Turkey. Results: Neuroinflammation is a very complex process with the contribution of many inflammatory cells and their mediators. PMF treatment may modulate the neuroinflammatory conditions in the central and peripheral neural tissues. Conclusions: The noninvasive PMF therapy, which has parameters that can be controlled and which has no side effects, is a nonpharmacological therapeutic option with pain-relief ability through strong control of central and peripheral neuroinflammation. Further studies are needed to explore how PMF therapy controls central and peripheral neuroinflammation in various diseases and conditions.

Pulsed magnetic field treatment ameliorates the progression of peripheral neuropathy by modulating the neuronal oxidative stress, apoptosis and angiogenesis in a rat model of experimental diabetes.

OBJECTIVE: The present study aimed to investigate the possible anti-neuropathic effects of daily pulsed magnetic field treatments (PMF) in streptozotocin (60 mg/kg) induced 4 weeks diabetic (type-1) wistar rats (6-8 months). MATERIALS AND METHODS: Body mass, blood glucose and thermal and mechanical sensations were evaluated during the PMF or sham-PMF in diabetic or non-diabetic rats (n = 7/group). After the measurements of motor nerve conduction velocities (MNCV), the levels of several biomarkers for oxidative stress, apoptosis and angiogenesis in spinal cord and sciatic nerve were measured. RESULTS: PMF for 4 weeks significantly recovered the MCNV (96.9% and 63.9%) and almost fully (100%) restored to the latency and threshold. PMF also significantly suppressed the diabetes induced enhances in biochemical markers of both neuronal tissues. CONCLUSIONS: Findings suggested that PMF might prevent the development of functional abnormalities in diabetic rats due to its anti-oxidative, anti-apoptotic and anti-angiogenic actions in neuronal tissues.

Neuroprotective and anti-neuropathic actions of pulsed magnetic fields with low frequencies in rats with chronic peripheral neuropathic pain.

The management of chronic peripheral neuropathic pain conditions with conventional treatments is still limited. In this present study, we aimed to determine the anti-neuropathic actions of pulsed magnetic field (PMF) treatments as a therapeutic. Effects of daily PMF treatments for 4 weeks were investigated by examining pain behaviors, hyperalgesia and allodynia, electrophysiological parameters, amplitude of compound action potential (CAP) and sciatic nerve conduction velocity (SNCV) and histopathological changes in rats with chronic constriction injury (CCI). Peripheral and central pro-inflammatory cytokines (TNF α, IL-1ß and IL-17), chemokines (CCL3 and CXCL1) and angiogenic factors (VEGF and bFGF) in sciatic nerves and spinal cord tissues were also measured for determining the possible molecular action mechanisms of PMF treatment. Hyperalgesia and allodynia were observed at the first week and lasted for 4 weeks after CCI. PMF treatments caused time-dependent anti-hyperalgesic and anti-allodynic effects. PMF treatment alleviated the histopathological consequences of CCI on sciatic nerve and significantly improved the amplitude of the CAP and SNCV. PMF treatment inhibited the pro-inflammatory molecules and promoted the anti-inflammatory cytokines in neural tissues. PMF treatment also suppressed the VEGF levels and enhanced the bFGF levels in both neural tissues. The results of the present study suggested that daily PMF treatment may have neuroprotective and anti-neuropathic pain actions in rats with CCI-induced neuropathy due to its modulating effects on neuro-inflammatory and neuro-angiogenic mediators in central and peripheral neural tissues.

Magnetic Field Exposure Modulates the Anti-Inflammatory Efficiency of Minocycline in Rats with Peripheral Acute Inflammation.

BACKGROUND AND OBJECTIVE: Microglial activation in spinal cord is key contributor and its inhibition by Minocycline (MCN) can result in anti-inflammatory actions. Effect of pulsed magnetic field (PMF) in living system is a very complex process and many biological and cellular processes can play key roles. In this study aimed to reveal the roles of PMF exposure on anti-inflammatory potentials of MCN treatment by evaluating the inflammatory profiles of either inflamed site or spinal cord. METHODS: In this study, we investigated the anti-inflammatory effects of PMF, MCN or their combination treatments in rats with carrageenan (CG)-induced peripheral inflammation by examining the cardinal signs, hyperalgesia, allodynia, edema and fever. The levels of various inflammation markers (tumor necrosis factor-α), interleukin (IL)-1ß, IL-6, IL-17, IL-4, IL-10, C-C motif chemokine ligand3 (CCL3), C-X-C motif chemokine ligand1 and myeloperoxidase were also measured in paw and spinal cord tissues. RESULTS: CG induced inflammation caused edema, fever, and hypersensitivities. MNC or PMF treatments ameliorated these responses by suppressing pro-inflammatory markers in both inflamed paw and spinal cord. Although anti-hypersensitive, anti-edematous and anti-pyretic actions of MCN or PMF, in combined treatments PMF exposure decreased the anti-hyperalgesic and anti-allodynic actions of MCN treatment. These may be associated with decreases in IL-4 and IL-10 levels and an increase in CCL3 level of spinal cord tissues. CONCLUSION: Present findings support that MCN or PMF has anti-inflammatory properties duo to the down-regulating central microglial and/or peripheral inflammatory markers. Our data showed here, for the first time, PMF exposure may suppress the anti-hypersensitive actions of MCN by modulating microglia function/phenotype and microglial markers.

Antiinflammatory properties of antiLy6G antibody disappear during magnetic field exposure in rats with carrageenan induced acute paw inflammation.

Antiinflammatory properties of pulsed magnetic field (PMF) treatments or administration of antiLy6G antibody have been previously reported. In this study, we hypothesized that, the combination of PMF treatments and antiLy6G administration may synergistically potentiate their antiinflammatory actions. The effects of the combination of PMF treatments and antiLy6G administration were investigated by examining the inflammatory signs, histopathological properties of the inflamed site, and measuring the macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) and myeloperoxidase (MPO) levels of inflamed paw tissues in rats with carrageenan-induced acute paw inflammation. In this present study, PMF treatments alone or administration of antiLy6G alone ameliorated the acute inflammation. However, their combination exacerbated the inflammatory signs, hyperalgesia, allodynia, edema and fever, and aggravated the inflammatory conditions by excessive infiltration of inflammatory cells to the inflamed site. These opposing effects of the combined treatments may correlate with enhanced levels of MIP-1α and MPO in inflamed paws. Present results indicated that the combination of the PMF treatments and antiLy6G administration may not provide additional benefits and may actually cause an aggravation of the acute inflammatory process. Findings may also suggest that during neutrophil or immune cell-targeted treatments for inflammatory states, magnetic field exposure may cause unexpected negative consequences.

Pro-inflammatory or anti-inflammatory effects of pulsed magnetic field treatments in rats with experimental acute inflammation.

In this study, we evaluated the possible effects of sequenced pulsed magnetic fields (PMF) of 1-mT treatments with designed different frequencies (PMF-1-1, 3, 5, 7 Hz or PMF-2-7, 9, 12, 14 Hz) on the inflammatory signs such as abnormal pain behaviors, hyperalgesia and allodynia, edema, and fever in carrageenan (CG)-induced hind paw inflammation model in rats. Paw tissues were also histologically examined. PMF exposure was applied 3 times in 24 h. CG injection gradually decreased the thermal latencies and mechanical threshold and caused significant increases in temperature and mass of paw. PMF treatments significantly reduced the temperature and mass in the paw of rats with inflammation. PMF-1 treatments caused significant increases in the latencies and thresholds. However, administration of PMF-2 treatment was significantly decreased the latency and threshold. Furthermore, the histological pieces of evidence also suggested the anti-inflammatory effects of PMF-1 treatments or inflammatory actions of PMF-2 treatments. Findings presented in this paper suggest that 1-mT PMF treatments may have anti-edematous and antipyretics activities in inflamed rats. However, the effects of PMF treatments on abnormal pain hypersensitivities may be different. PMF treatments may make inflammatory pain relief or worse in inflamed rats depending on the PMF frequencies in sequence.

Effects of immune cell-targeted treatments result from the suppression of neuronal oxidative stress and inflammation in experimental diabetic rats.

In this study, we hypothesized that reduction of immune cell activation as well as their oxidant or inflammatory mediators with minocycline (MCN), liposome-encapsulated clodronate (LEC), or anti-Ly6G treatments can be neuroprotective approaches in diabetic neuropathy. MCN (40 mg/kg) for reduction of microglial activation, LEC (25 mg/kg) for of macrophage inhibition, or anti-Ly6G (150 µg/kg) for neutrophil suppression injected to streptozotocin (STZ)-induced diabetic rats twice, 3 days, and 1 week (half dose) after STZ. Animal mass and blood glucose levels were measured; thermal and mechanical sensitivities were tested for in pain sensations. The levels of chemokine C-X-C motif ligand 1 (CXCL1), CXCL8, and C-C motif ligand 2 (CCL2), CCL3, and total oxidant status (TOS) and total antioxidant status (TAS) were measured in the spinal cord and sciatic nerve tissues of rats. LEC significantly reduced the glucose level of diabetic rats compared with drug control. However, MCN or anti-LY6G did not change the glucose level. While diabetic rats showed a marked decrease in both thermal and mechanical sensations, all treatments alleviated these abnormal sensations. The levels of chemokines and oxidative stress parameters increased in diabetic rats. All drug treatments significantly decreased the CCL2, CXCL1, and CXCL8 levels of spinal cord tissues and ameliorated the neuronal oxidative stress compared with control treatments. Present findings suggest that the neuroprotective actions of MCN, LEC, or anti-Ly6G treatments may be due to the modulation of neuronal oxidative stress and/or inflammatory mediators of immune cells in diabetic rats with neuropathy.

Anti-inflammatory properties of Liposome-encapsulated clodronate or Anti-Ly6G can be modulated by peripheral or central inflammatory markers in carrageenan-induced inflammation model.

Overproduction of inflammatory markers by immune cells, such as macrophages and neutrophils, is one of the main reasons for many inflammatory conditions and inhibiting or suppressing of their production by cell depletion may provide new therapeutic targets or approaches to prevent a variety of inflammatory conditions. In this study, we examined the possible effects of anti-Ly6G-mediated systemic neutrophil depletion and liposome-encapsulated clodronate (LEC)-mediated systemic macrophage depletion on the inflammatory signs (thermal hyperalgesia, mechanical allodynia, oedema and fever) and measured the levels of various inflammation markers (tumour necrosis factor-α (TNF-α), interleukins (IL)-1ß, IL-4, IL-10, macrophage inflammatory protein-1 alpha (MIP-1α/CCL3) and myeloperoxidase (MPO) in paw and spinal cord tissues in carrageenan (CG)-induced hindpaw inflammation model in rats. CG injection into the paw caused inflammation characterized by redness, swelling, heat and pain hypersensitivities. Anti-Ly6G or LEC significantly ameliorated the pain behaviours, and decreased the oedema and fever. Efficacies of anti-Ly6G or LEC on inflammatory responses changed depend on the degree of inhibition in inflammatory markers of inflamed paw or spinal cord. Anti-inflammatory properties of anti-Ly6G or LEC suggest that macrophages and/or neutrophil-mediated inflammatory cascade in inflamed site and spinal cord which can play key roles in inflammatory pain responses. These systemic or peripheral inflammatory mediators may be therapeutic targets in the treatment of many inflammatory conditions and related various diseases.

Pain-Relieving Effectiveness of Co-Treatment with Local Tramadol and Systemic Minocycline in Carrageenan-Induced Inflammatory Pain Model.

In this study, we tested our working hypothesis that inhibiting the activation of microglia by systemic minocycline treatments can decrease the dosage of local tramadol injection in inflammatory pain. This study was therefore aimed to evaluate the actions of intraplantarly injected tramadol, intraperitoneally injected minocycline, or their combined treatments on the inflammation-induced hypernociception (thermal hyperalgesia, mechanical allodynia), edema, and pro- and anti-inflammatory cytokine levels of paw and spinal cord tissues in a rat model of carrageenan-induced hindpaw inflammation. While local tramadol or systemic minocycline caused a significant anti-hypernociceptive effect their combined treatments significantly enhanced anti-hypernociceptive action compared to each agent applied alone. Also anti-edematous actions of combined treatment were higher than that of their individual administrations. In addition, combined treatment significantly decreased the level of the pro-inflammatory cytokines and caused significant increases in anti-inflammatory cytokine level of paw and spinal cord tissues. The present finding can suggest that combined treatments of local tramadol and systemic minocycline may decrease the dose requirements for anti-hypernociceptive actions of local tramadol and this combination therapy might be a beneficial option for the inflammatory pain relief.

Pulsed magnetic field treatment as antineuropathic pain therapy.

No satisfactory effective therapy is still available to treat trauma- or disease-induced neuropathic pain, and current available treatment options have several side effects. Pulsed magnetic field (PMF) treatments are receiving growing interest as a therapeutic approach for several neuronal diseases. Although the exact mechanism of action of PMF treatments is unknown, reported findings represent a promising alternative therapeutic choice for the management of neuropathic pain. PMF treatments can supply new strategies for the therapy of life-threatening neuropathic pain due to its antihyperglycemic, anti-inflammatory, antihyperalgesic, antiallodynic, and neuroimmunomodulatory actions. In this review, I summarized the several recent findings about antineuropathic actions of PMF treatment in experimental animals with neuropathic pain induced by disease and/or damage.

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-1ß, 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. © 2017 Wiley Periodicals, Inc.

Impact of Magnetic Field on Pressures of Programmable Cerebrospinal Fluid Shunts: An Experimental Study.

AIM: To investigate whether programmable cerebrospinal fluid (CSF) shunts are influenced by exposure to the magnetic field and to compare the effects of magnetic field in 4 different brands of programmable CSF shunts. MATERIAL AND METHODS: This experimental study was performed in the laboratory using a novel design of magnetic field. Four types of programmable CSF shunts (Miethke®, Medtronic®, Sophysa® and Codman®Hakim®) were exposed to the magnetic field generated by an apparatus consisting of Helmholtz coil for 5 minutes. In every CSF shunt, initial pressures were adjusted to 110 mm H2O and pressures after exposure to magnetic field were noted. These measurements were implemented at frequencies of 5 Hz, 20 Hz, 30 Hz, 40 Hz, 60 Hz and 80 Hz. In each type, three shunts were utilized and evaluations were made twice for every shunt. RESULTS: At 5, 30, 40 and 60 Hz, Groups 1, 2 and 3 had significantly higher average pressures than Group 4. At 20 and 80 Hz, Groups 1 and 2 had notably different pressure values than Groups 3 and 4. Group 3 displayed the highest pressure, while Group 4 demonstrated the lowest pressure. CONCLUSION: Exposure to magnetic fields may affect the pressures of programmable CSF shunts. However, further controlled, clinical trials are warranted to elucidate the in-vivo effects of magnetic field exposure.

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.

Frequency-dependent effects of sequenced pulsed magnetic field on experimental diabetic neuropathy.

PURPOSE: Pulsed magnetic field (PMF) as an important non- invasive alternative therapeutic option has been investigated in several pre-clinical and clinical studies. We also hypothesized that sequenced PMF formed with different frequencies can modulate the diabetes-induced neuropathic signs differently. MATERIALS AND METHODS: Therapeutic actions of sequenced PMF including 1, 5, 1, 5 Hz (low (L)-PMF) or 30, 40, 30, 40 Hz (high (H)-PMF) were examined on improving signs and symptoms of diabetic neuropathic pain in the streptozotocin-induced diabetic rat models by measuring nociceptive parameters such as hyperalgesia and allodynia, and various cytokine levels (tumor necrosis factor [TNF]-alpha, interleukin [IL]-1 beta, IL-6 and IL-10) of spinal cord and sciatic nerve tissues. RESULTS: Ameliorating potential of L-PMF application on signs of diabetes is significantly higher than those of H-PMF. L-PMF partially attenuated the diabetes-induced increase in the blood glucose level, enhanced the decreased thresholds and latency during the experiments. Diabetes enhanced the pro-inflammatory cytokine, TNF-alpha, IL-1 beta and IL-6, levels in spinal cord and sciatic nerve of rats. L-PMF treatments to diabetic rats decreased these, but enhanced the production of anti-inflammatory cytokine, IL-10. CONCLUSIONS: The present results demonstrated that sequenced L-PMF treatment can relieve neuropathic signs of diabetes in rats. Anti-hyperglycemic, anti-allodynic and anti-hyperalgesic effects of L-PMF treatment can be closely correlated with each other. Furthermore, decreasing actions of L-PMF on pro-inflammatory/anti-inflammatory cytokine ratio can suggest that the therapeutic potential of L-PMF in diabetes induced neuropathy may involve the regulation of the neuroinflammatory/neuroimmune processes.

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

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.

Anti-inflammatory and Anti-nociceptive Actions of Systemically or Locally Treated Adipose-Derived Mesenchymal Stem Cells in Experimental Inflammatory Model.

Cell-based therapies using mesenchymal stem cells provide hopeful results. Therefore, in this present study, possible anti-inflammatory and anti-nociceptive actions of locally or systemically treated adipose-derived mesenchymal stem cells (ADMSCs) investigated in experimental inflammation model. ADMSCs were isolated from a male Wistar rat under anesthesia, and then they were cultured and expanded for transplantation in all the experimental animals. Effects of intraperitoneal or intraplantar ADMSC treatments on the hallmarks of the inflammatory nociception, such as hyperalgesia, allodynia, edema, and several biochemical parameters were investigated using a well-established carrageenan (CG)-induced hindpaw inflammation model in male rats. Both local and systemic ADMSC treatment increased the latencies, thresholds, and the development of edema in a time-dependent manner. In addition, administration of ADMSC suppressed the increased level of interleukin (IL)-1ß, IL-6, and nitric oxide (NO), but further enhanced that of IL-10. Locally treated ADMSC at inflammatory sites effectively suppressed the CG-induced inflammatory responses when compared to the intraperitoneal route of administration. Findings suggest that therapeutic potential of ADMSC can change depending on its route of administration. Local ADMSC treatments may suppress the development of inflammatory-nociception and edema by decreasing the production of pro-inflammatory cytokines and NO level and increasing the anti-inflammatory cytokine production at inflammatory sites.

Modulating actions of NMDA receptors on pronociceptive effects of locally injected remifentanil in diabetic rats.

BACKGROUND: In this study, we investigated the effects of locally (intraplantar) applied remifentanil, a µ opioid receptor agonist, to the paws and tested whether locally N-methyl d-aspartate (NMDA) receptors agonist or antagonist can modify remifentanil-induced effects in diabetic rats. METHODS: Effects of locally (intraplantar) remifentanil, NMDA and MK801 or their combinations were investigated by measuring the latencies, thresholds and two biochemical parameters (malondialdehyde (MDA) and nitric oxide (NO)), in streptozotocin induced diabetic rats. RESULTS: Diabetic rats exhibited hyperalgesia and allodynia and remifentanil treatment aggravated the hyperalgesia and allodynia. The hyperalgesic and allodynic effects of remifentanil decreased in diabetic rats as compared to healthy rats. MK801 suppressed the hyperalgesic and allodynic actions of remifentanil in diabetic rats. However, hyperalgesic and allodynic actions of NMDA increased in diabetic rats. In contrast to age matched group, the combination of NMDA and remifentanil did not produce synergistic actions in diabetic rats. The levels of MDA and NO in the paw tissues of the diabetic rats significantly increased. MK801 significantly decreased NO levels, but not MDA, in diabetic rats. CONCLUSIONS: The hyperalgesic and allodynic actions of locally treated remifentanil may decrease in diabetic conditions. Increases in NMDA receptors activation, reactive oxygen species production and NO release may modify the sensitivity to remifentanil in diabetes induced neuropathic pain states.

Preventive and therapeutic effects of a beta adrenoreceptor agonist, dobutamine, in carrageenan-induced inflammatory nociception in rats.

We hypothesized that locally administrated ß-adrenoreceptor agonist can modulate the inflammatory nociceptive parameters in carrageenan (CG)-induced peripheral inflammatory pain. This study was therefore aimed to assess the preventive and therapeutic effects of a ß-agonist, dobutamine, by investigating its pretreatment and posttreatment actions on the inflammation-induced hypersensitivities (thermal hyperalgesia, mechanical allodynia) to cutaneous stimulation, edema, and several biochemical oxidant and anti-oxidant parameters in a rat model of CG-induced hind paw inflammation. Effects of dobutamine were compared with those of esmolol, a ß-adrenoreceptor antagonist. CG injection to healthy rats lowered the thermal latencies (from 10.1 ± 0.2 to 4.9 ± 0.1 s) and mechanical thresholds (from 32.9 ± 0.5 to 18.9 ± 1.3 g) and caused the hyperalgesia and allodynia. In CG-induced inflamed paws, while intraplantar esmolol treatment (1 mg) produced significant decreases in latencies (4.1 ± 0.1 s) and thresholds (15.2 ± 2.4 g), dobutamine (1 mg) increased the latencies (11.3 ± 0.5 s) and thresholds (26.3 ± 2.8 g). In contrast to esmolol, dobutamine increased the superoxide dismutase level and decreased the myeloperoxidase, malondialdehyde, and nitric oxide levels in CG-induced inflamed paws. The present results can reveal that ß-adrenoreceptors may play a role in inflammatory nociceptive processes, and locally treated ß-adrenoreceptor agonists such as dobutamine can be a preferable, appropriate choice for the management of inflammatory nociception due to their preventive and therapeutic effects on CG-induced peripheral inflammatory nociception.

Pain-relieving effects of pulsed magnetic fields in a rat model of carrageenan-induced hindpaw inflammation.

PURPOSE: Many strategies have been investigated to exclude the several side-effects of pharmacological or invasive treatments. Non-invasive pulsed magnetic field (PMF) treatment with no toxicity or side-effects can be an alternative to pharmacologic treatments. The purpose of this study was, therefore, to investigate the pain-relieving effects of PMF treatment in the inflammatory pain conditions. MATERIALS AND METHODS: Effects of PMF treatment on the hallmarks of the inflammatory pain indices such as hyperalgesia, allodynia, edema and several biochemical parameters that evaluate oxidative stress were investigated using a well established carrageenan (CAR)-induced hindpaw inflammation model in rats. RESULTS: CAR injection lowered the paw withdrawal thermal latencies (hyperalgesia) and mechanical thresholds (allodynia). CAR also decreased the superoxide dismutase (SOD), catalase (CAT) and glutathione peroxidase (GPx) levels and increased malondialdehyde (MDA) levels compared with healthy rat paw tissues. PMF treatment produced significant increases in the thermal latencies and mechanical thresholds in CAR-injected paws. In the inflamed paw tissues, PMF increased the activities of SOD, CAT and GPx and decreased MDA level. We also demonstrated that PMF decreased paw mass indicating that it has an anti-edematous potential. CONCLUSIONS: The present results reveal that PMF treatment can ameliorate the CAR-induced inflammatory pain indices such as mechanical allodynia, thermal hyperalgesia and edema, and attenuate the oxidative stress. The action mechanisms of PMF in CAR-induced inflammation might be related to the increases in the levels of antioxidant enzymes in inflamed tissues. The findings suggest that PMF treatment might be beneficial in inflammatory pain conditions.

Dexmedetomidine modifies uterine contractions in pregnancy terms of rats.

OBJECTIVES: The present study was aimed at determining the effective doses of Dexmedetomidine (Dex) involved in amplitude of contraction-force and frequency of uterine rings in pregnancy terms of rats. All experiments involving animal subjects were carried out with the approval of animal care and use Ethical Committee of Cukurova University. Experiments were performed on female Albino-Wistar rats (200-260 g; n = 40). MATERIALS AND METHODS: Uterine rings from pregnant rats were placed in organ bath with Krebs and calcium ion (Ca(2+))-free solutions to record and exposed to serially increasing log10 concentrations of Dex. RESULTS: In Krebs solution, while Dex caused an increase in the spontaneous contraction-forces in all pregnancy terms of rats in a significant dose-dependent manner, it led to a decrease in contraction-frequency in late-pregnancy term of rats. In Ca(2+)-free, the spontaneous contraction-force decreased in late-pregnancy term and increased in early and middle-pregnancy terms. In addition, while Dex increased the contraction-frequency in early and middle-pregnancy terms, it decreased in late-pregnancy term in a dose-dependent manner. STATISTICAL ANALYSIS USED: The data were subjected to one-way analysis of variance. Repeated measures were employed for comparison of several group means through the Tukey post-hoc test (SPSS 10.00 Inc., Chicago, Ill, USA). P < 0.05 was considered statistically significant. CONCLUSIONS: This study suggested that Dex might differently alter the spontaneous contraction-forces and contraction-frequencies of uterine rings in all pregnancy terms of rats in Krebs and Ca(2+)-free solutions.