Effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain induced by CFA adjuvant

Background: Rheumatoid arthritis is a type of inflammatory pain and is an autoimmune and chronic inflammatory disease which can lead to hyperalgesia, edema and decreased motor activity in affected area. Mesenchymal stem cells conditioned medium (MSC-CM) has anti-inflammatory mediators which can regulate the immune responses, alleviate inflammatory symptoms and has a paracrine effects too. The aim of this study was to evaluate the effects of mesenchymal stem cells conditioned medium on behavioral aspects of inflammatory arthritic pain which induced by CFA adjuvant.Materials and Methods: Complete Freund’s adjuvant (CFA)-induced arthritis (AA) was caused by single subcutaneous injection of CFA into the rats hind paw on day zero. MSC-CM was administered daily and intraperitoneal during the 21 days of the study after CFA injection. Hyperalgesia and edema were assessed on days 0, 7, 14 and 21 of the study respectively with radian heat and plethysmometer instrument.Results: The results of this study indicated the significant roles of MSC-CM in betterment of inflammatory symptoms such as hyperalgesia and edema during different stages of inflammation caused by CFA. The continuing injection of MSC-CM could reduce the inflammatory symptoms.Conclusion: Long term treatment by MSC-CM can alleviate hyperalgesia and edema and decrease those to the level of the time before induction of inflammation.  

Microglia are involved in pain related behaviors during the acute and chronic phase of arthritis inflammation

Abstract Background: Pain is one of the main protests of inflammatory diseases, hence, understanding the mechanisms which involved in the induction and persistence of pain is essential. Microglia is a contributing factor in the onset and maintenance of inflammation. Increased microglial   activation increases the level of central pro-inflammatory cytokines and the development of central sensitization following inflammation. The aim of this study was evaluate the relation of spinal microglia activity with pain related behaviors during Complete Freund’s adjuvant (CFA)-induced inflammation. Materials and Methods: Inflammation caused by subcutaneous injection of Complete Freund’s adjuvant (CFA) in a single dose to the animals right hind paw. The edema and hyperalgesia caused by inflammation, respectively are measured by Plethysmometer and Radiant Heat, on days 0,7,14 and 21. Spinal Iba-1 protein expression was detected by Western blotting. Minocycline hydrochloride (Sigma, U.S.A) was administered i.p. at a dose of 40mg/kg daily. Results: Our study findings indicated that CFA injection to right hindpaw of rats increased paw volume and hyperalgesia significantly during different stages of study, while Minocycline treatment significantly reduced paw volume and hyperalgesia. CFA injection into the right hindpaw of the rat increases the expression of molecules Ionized calcium binding adaptor molecule -1 (Iba-1) on different days of study, while Minocycline administration reduced spinal Iba-1 expression significantly compared to the CFA group. Conclusion: The results of this study indicated the significant roles of microglia activation in deterioration of pain related behaviors during different stages of CFA-induced inflammation. The steady injection of Minocycline (as a microglia inhibitor) could reduce the inflammatory symptoms. Keywords: Inflammation, pain, microglia, minocyclin

Bidirectional effects of serum TNF alpha level and spinal P38MAPK phosphorylation on hyperalgesia variation during CFA-induced arthritis

Regarding the role of TNFα in the induction of hyperalgesia, the dual suggested roles of the Pp38 MAPK intracellular pathway in the emergence of symptomatic inflammation, we aimed to investigate the bidirectional effects of serum TNFα level and p38 MAPK phosphorylation on hyperalgesia variation during different stages of adjuvant-induced arthritis. Hyperalgesia and edema were assessed at 0, 3, 7, 14, and 21 days of study after arthritis induction by CFA. Anti-TNFα and Pp38 inhibitor were administered during the 21 days of study. Receptor and intra-cellular enzyme expression were detected by western blotting. Anti-TNFα administration in the AA group decreased paw volume and hyperalgesia until the 14th day of study; on the 21st day, those symptoms increased. Daily administration of anti-TNFα antibody caused significant decrease in spinal mOR protein and Pp38/p38 MAPK enzyme level expression on the 14th and 21st days compared to the AA control group. Our data suggested that phosphorylation of spinal p38 MAPK enzyme played an important role in bidirectional effects of serum TNFα on inflammatory symptoms via spinal mOR expression variation

Immune and Opioid system interaction in pain modulation

Background: Inflammatory pain is caused by direct stimulation of nociceptors with the release of inflammatory mediators. Several studies about the roles of immune and opioid systems in the pain process have suggested that their crosstalk may have effective in pain modulation. Accordingly, the purpose of this study was review the effect of immune and opioid systems on pain modulation.Evidence acquisition: The increasing demand for mitigating inflammatory pain has led to the introduction of the effect of immune and opioid system interaction in pain modulation. Our literature reviewed 61 articles from 1991 to 2016.Results: In this study, we reviewed most of the existing papers on the role of opioid system in pain modulation especially with a focus of the immune system efficacy. Our review suggested that there is a close correlation between the expression of cytokines and opioid receptors and in the process of inflammatory pain where immune cells have a notable effect on the expression of cytokines and opioid receptors. In the process of inflammation, different types of immune cells constitute a major source of opioid peptides. The endogenous opioids could modulate either their own secretion or secretion of other cytokines. They have also anti-nociceptive and anti-inflammatory effects.Conclusion: Exacerbation of immune and opioid system reactions via correlation between cytokines and opioid peptides in the context of inflammatory pain arises the possibility of the role of interaction of these two important systems in the pain process. Keywords: inflammatory pain, opioids, immune system, cytokines, hyperalgesi

Inhibitory Effect of Black and Red Pepper and Thyme Extracts and Essential Oils on Enterohemorrhagic Escherichia coli and DNase Activity of Staphylococcus aureus

Abstract In this study, extracts and essential oils of Black and Red pepper and Thyme were tested for antibacterial activity against Escherichia coli O157: H7 and Staphylococcus aureus. Black and Red pepper and Thyme were provided from Iranian agricultural researches center. 2 g of each plant powder was added to 10 cc ethanol 96°. After 24 h, the crude extract was separated as an alcoholic extract and concentrated by distillation method. Plants were examined for determining their major component and essential oils were separated. Phytochemical analyses were done for detection of some effective substances in extracts. The antibacterial activity against Escherichia coli O157: H7 and Staphylococcus aureus was tested and the results showed that all extracts and essential oils were effective and essential oils were more active. The extracts and oils that showed antimicrobial activity were later tested to determine the Minimum Inhibitory Dilution (MID) for those bacteria. They were also effective on the inhibition of DNase activity. This study was indicated that extracts and essential oils of Black and Red pepper and Thyme can play a significant role in inhibition of Escherichia coli O157: H7 and Staphylococcus aureus

Reduction of chronic non-specific low back pain: A randomised controlled clinical trial on acupuncture and baclofen

<p>Abstract</p> <p>Background</p> <p>Chronic non-specific low back pain (LBP) is a prevalent (80%) and multi-dimensional illness. This study aims to test whether acupuncture, baclofen, or combined treatment with acupuncture and baclofen alleviates symptoms of non-specific chronic LBP in men.</p> <p>Methods</p> <p>Eight-four (84) men aged 50-60 years with non-specific chronic LBP were randomly assigned to four groups: the baclofen group received only baclofen (30 mg/day); the acupuncture group received only acupuncture at selected acupoints; the acupuncture + baclofen group received combined treatment with acupuncture and baclofen treatments; and the control group received no pain reduction treatment. After five weeks of treatment, visual analogue scale (VAS) and self-reported pain disability with the Roland-Morris Disability Questionnaire (RDQ) were conducted for outcome measures.</p> <p>Results</p> <p>After treatment, the baclofen, acupuncture and acupuncture + baclofen groups all had lower VAS and RDQ scores. Significantly higher reduction and improvement in VAS and RDQ scores were found in the acupuncture and acupuncture + baclofen groups compared to the baclofen group.</p> <p>Conclusion</p> <p>The present study indicates that the combined treatment of acupuncture and baclofen is more effective than baclofen treatment alone to reduce pain in patients with non-specific chronic LBP.</p> <p>Trial registration number</p> <p>ACTRN12609000698279</p

Research Paper: The Impact of Synovial NF-ĸB Activation on Apoptosis Pattern Change During Adjuvant-induced Inflammation

Introduction: Apoptosis dysregulation plays a substantial role in the pathophysiology of chronic inflammation and its related symptoms such as edema. Regulation of NF-ĸB activation is involved in apoptosis pattern change. The current study aimed at verifying the effects of local inflammation on edema and changes in apoptotic markers, and investigating the possible role of NF-ĸB in apoptosis pattern change during different stages of complete Freund&rsquo;s adjuvant (CFA)-induced knee arthritis in rats. Methods: A total of 96 male Wistar rats were divided into different experimental groups. Arthritis was evoked into the right knee articular joint. Changes made in knee edema were assessed by caliper on the days 0, 7, 14, and 21 of the study. Synovial NF-ĸB and levels of apoptotic markers were evaluated during different stages of the study using Western blot technique.&nbsp; Results: CFA injection caused intense edema during the whole study period. Synovial NF-ĸB level increased during the whole study period. The level of apoptotic markers increased during the acute phase of study. But during chronic phase, the apoptosis level decreased. Inh-NF-ĸB administration increased synovial apoptosis during the whole study period. Conclusion: It seems that apoptosis pattern change plays an important role in the progression and modulation of CFA-induced inflammation and its related symptoms. Also, it can be concluded that synovial NF-ĸB had a crucial role in synovial apoptosis change during the study period

The Effect of Orally Administered Probiotics on the Behavioral, Cellular, and Molecular Aspects of Adjuvant-Induced Arthritis

Introduction: Rheumatoid Arthritis (RA) is a chronic autoimmune disease, which is accompanied with pain, hyperalgesia, and edema. Overproduction of pro-inflammatory cytokines and activation of intracellular signaling pathways sustain the RA symptoms considerably. There is a strong correlation between the expression of cytokines and opioid receptors in the arthritis process. Studies have shown that probiotics via different pathways such as reducing the levels of pro-inflammatory cytokines can alleviate inflammatory symptoms. Therefore, based on the crucial role of cellular and humoral immunity in induction of RA symptoms and potency of probiotics in modulation of immune responses, the purpose of this study was to investigate the effect of orally administered probiotics on the behavioral, cellular and molecular aspects of adjuvant-induced arthritis in male Wistar rats. Methods: Complete Freund Adjuvant (CFA)-induced arthritis was caused by single subcutaneous injection of CFA into the rat hind paw on day 0. Different doses of probiotics (1/250, 1/500 and 1/1000 [109 CFU/g]) were administered daily (gavage) after CFA injection. Hyperalgesia, edema, serum IL-1&beta; levels, &mu;-Opioid Receptor (MOR) expression, and p38MAPK (Mitogen-Activated Protein Kinase) activities were assessed on days 0, 7, 14 and 21 of the study. Results: The results of this study indicated the efficacy of probiotics in reducing hyperalgesia, edema, serum levels of Interleukin-1&beta;, and p38MAPK pathway activity during different phases of arthritis as well as increasing the expression of MORs during chronic phase of CFA-induced arthritis. Conclusion: It seems that probiotics can effectively reduce inflammatory symptoms by inhibiting the intracellular signaling pathway and cytokine production