[Role of serum interleukin-6 level on hyperalgesia and spinal mu-opioid receptor expression during the complete Freund's adjuvant- induced chronic inflammation]

Interleukin [IL-6] is known to cause pro-and anti-inflammatory effects during different stages of inflammation. The purpose of this study was to elucidate the effects of IL-6 on hyperalgesia, edema and the changes in the spinal mu opioid receptor expression during different stages of complete Freund's adjuvant [CFA]-induced arthritis [AA] in rats. In this study, AA was induced by a single subcutaneous injection of CFA into rats' hindpaw. The rats with arthritis were divided into four groups, each consisted of three subgroups [n=6]. Anti-IL-6 was administered either daily or weekly during the 21-day study period. Spinal mu-opioid receptor [mOR] expression was detected by Western blotting. Daily treatment with an anti-IL-6 antibody significantly decreased the paw edema in the AA group compared to the control one [P=0.001], but daily and weekly anti-IL-6 administrations significantly increased the hyperalgesia in the antibody-treated group on the 14th and 21st days post-treatment [P=0.001, P=0.01, respectively]. The administration of IL-6 antibody not only increased hyperalgesia in a time-dependent manner, but also caused a significant reduction in the spinal mOR expression on the 14th and 21st days post-CFA injection [P=0.01, P=0.001, respectively]. Results can indicate the importance of a time-dependent relationship between the serum IL-6 level and hyperalgesia during the AA. Moreover, the results suggest that the stages of inflammation in AA must be considered for anti-hyperalgesic and anti-inflammatory interventions via anti-IL-6 antibody treatment

[ effects of pretreatment with achillea santolina and stachys athorecalyx extracts on CFA-induced acute inflammation in male rats]

Inflammatory symptoms, hyperalgesia and edema, as a physiologic responses for stimulus can mediate via different mediators such as cytokines. Medicinal plants are an important source of substances which are claimed to induce anti-inflammatory effects. Regarding to these and on account of the Interlukine-6 roles in hyperalgesia and edema induction, the aim of this study explained to investigation of the pre-treatment effects of Achillea santolina and Stachys athorecalyx extracts on inflammation which induced by CFA in male Wistar rats. Methanolic and defatted extractions were done on aerial parts of the both plants. Achillea santolina and Stachys athorecalyx 50, 100 and 200 mg/kg doses of extracts were selected for treatment. Results indicated that pre-treatment with defatted and methanolic extracts of S. athorecalyx significantly decrease CFA-induced hyperalgesia and edema dose-dependently. At same situation only methanolic extract of A. santolina was effective in inflammatory signs reduction. It can concluded that A. santolina and S. athorecalyx extracts can be effective candidate for pre-treatment of inflammation, but the effective substances of them are different and need to be more investiged

[Behavioral responses and Pre-emptive effect of MK-801 and morphine using SNI model in adult rat]

Neuropathic pain syndromes are changes resulted from damage to nervous system. Since, treatments of neuropathic pain are poorly understood, existing treatments are often ineffective, and also experimental studies have documented that MK-801, a NMDA receptor antagonist, attenuates neuropathic pain, the purpose of this study was to investigate the behavioral responses and involvement of pre-emptive treatment of morphine and / or NMDA receptor antagonist MK-801, in Spared Nerve Injury [SNI] model of neuropathic pain. Experiments were performed on six groups [n=8] of male Sprague-Dawley rats [230-280g]. Two animal groups were injected MK-801 [0.3 mg/kg, 20 min before, and 6 h after the operation] or morphine [8 mg/kg, 30 min prior to the operation]. The third group was received both drugs with the same doses and protocols. Finally, the fourth group was received an equal volume of saline. Then, SNI procedure was performed by a ligation and axotomy of the tibial and common peroneal nerves and the sural nerve was left intact. The animals were tested for allodynia and hyperalgesia reactions at 0, 3, 7, 14, 21 and 28 days after performing SNI procedure of the sciatic nerve. Statistical analysis was performed using repeated measures ANOVA and the Tukey HSD test. Our data revealed that the SNI produces mechanical and cold allodynia and a hypersensitivity to noxious stimulations. Co-injection of morphine and MK-801 markedly declined cold allodynia at the day 14 [P<0.05] when compared with the saline group. The results of present study demonstrate that SNI model importantly influences the behavioral responses to both thermal and mechanical stimulations. It seems that co-administration of both drugs attenuates neuropathic pain in rat

Role of saphenous nerve in the behavioral responses of neuropathic pain - due to chronic constriction injury in rats

The chronic constriction injury [CCI] was introduced by Bennett and Xie in 1988 as an animal model of peripheral mononeuropathy. In this model, serious sensitivity to the thermal and mechanical allodynia and hyperalgesia is increased the areas in which sciatic nerve innervated. The spread of receptive fields of the saphenous nerve which innervates the medial part of the foot. In this study, we have examined the behavioral effects of the section of saphenous nerve at the time of applying CCI. Adult male Sprague - Dawley strain, with the weight 200 - 300 grs, used for experiments. Animals divided into four groups: sham operated, CCI group, cut of saphenous nerve [saph.] and CCI +/- saph. Two weeks after post operation, animals tested for behavioral responses: thermal allodynia [acetone blob and immersion of hind paw in 10[°C] water] thermal hyperalgesia [immersion of hind paw in 42[°C] water] mechanical allodynia [Von Frey], mechanical hyperalgesia [Pin Prick] and usage of damage paw. All symptoms of the neuropathic pains were appeared among all animals which went under CCI. CCI + Saph group showed analgesia, thermal allodynia and hyperalgesia, mechanical hyperalgesia and also usage of damage paw, except in mechanical allodynia. Results indicated that saphenous nerve may affect on behavioral responses of neuropathic pain related CCI. Saphenous nerve [as a neighboring with sciatic nerve] may affect on behavioral responses of neuropathic pain, probably by making collateral branches which may penetrate into the damage area

[Study of chronic oral administration of verapamil on immunologic and hematologic parameters of male rats]

Introduction: Verapamil, a phenylalkylamin -type ca[2+] channel blocker, is widely used in the treatment of cardiovascular diseases

Material and Methods: In this study , the chronic effects of oral administration of the drug on hematologi and immunologic parameters of male Wistar rats have been studied. Verapamil was administered orally at dosages of 10, 20, 50 mg/kg for two months, while control rats received only distilled water. We studied leukocyte and erythrocyte counts by use of light microscopy

Results: The lymphocyte counts were decreased [%10] in rats treated with 20, 50 mg/kg of verapamil compared to control group. The monocyte counts were signifigantly increased [%5-8] at the end of treatment in the verapamil group. There were no significant differences in the body weight, total white and red blood cell counts, and neutrophil count compared to control group

Conclusion: These results should be taken into consideration in the chronic treatment of patients with verapamil and they suggest that immune parameters of such patients should be monitored during the treatment course