Minocycline effects on IL-6 concentration in macrophage and microglial cells in a rat model of neuropathic pain

Background: Evidence indicates that neuropathic pain pathogenesis is not confined to changes in the activity of neuronal systems but involves interactions between neurons, inflammatory immune and immune-like glial cells. Substances released from immune cells during inflammation play an important role in development and maintenance of neuropathic pain. It has been found that minocycline suppresses the development of neuropathic pain. Here, we evaluated the analgesic effect of minocycline in a chronic constriction injury [CCI] model of neuropathic pain in rat and assessed IL-6 concentration from cultured macrophage and microglia cells

Methods: Male Wistar rat [n=6, 150-200 g] were divided into three different groups: 1] CCI+vehicle, 2] sham+vehicle, and 3] CCI+drug. Minocycline [10, 20, and 40 mg/kg] was injected one hour before surgery and continued daily to day 14 post ligation. Von Frey filaments and acetone, as pain behavioral tests, were used for mechanical allodynia and cold allodynia, respectively. Experiments were performed on day 0 [before surgery] and days 1, 3, 5, 7, 10, and 14 post -injury. At day 14, rats were killed and monocyte-derived macrophage from right ventricle and microglia from lumbar part of the spinal cord were isolated and cultured in RPMI and Leibovitz's media, respectively. IL-6 concentration was evaluated in cell culture supernatant after 24 h

Results: Minocycline [10, 20, and 40 mg/kg] attenuated pain behavior, and a decrease in IL-6 concentration was observed in immune cells compared to CCI vehicle-treated animals

Conclusion: Minocycline reduced pain behavior and decreased IL-6 concentration in macrophage and microglial cells

The Attenuation of Pain Behavior and Serum COX-2 Concentration by Curcumin in a Rat Model of Neuropathic Pain

BACKGROUND: Neuropathic pain is generally defined as a chronic pain state resulting from peripheral and/or central nerve injury. There is a lack of effective treatment for neuropathic pain, which may possibly be related to poor understanding of pathological mechanisms at the molecular level. Curcumin, a therapeutic herbal extract, has shown to be effectively capable of reducing chronic pain induced by peripheral administration of inflammatory agents such as formalin. In this study, we aimed to show the effect of curcumin on pain behavior and serum COX-2 level in a Chronic Constriction Injury (CCI) model of neuropathic pain. METHODS: Wistar male rats (150-200 g, n = 8) were divided into three groups: CCI vehicle-treated, sham-operated, and CCI drug-treated group. Curcumin (12.5, 25, 50 mg/kg, IP) was injected 24 h before surgery and continued daily for 7 days post-surgery. Behavioral tests were performed once before and following the days 1, 3, 5, 7 after surgery. The serum COX-2 level was measured on day 7 after the surgery. RESULTS: Curcumin (50 mg/kg) decreased mechanical and cold allodynia (P < 0.001) and produced a decline in serum COX-2 level (P < 0.001). CONCLUSIONS: A considerable decline in pain behavior and serum COX-2 levels was seen in rat following administration of curcumin in CCI model of neuropathic pain. High concentration of Curcumin was able to reduce the chronic neuropathic pain induced by CCI model and the serum level of COX-2.

Anti-allodynic effect of Nefopam and Morphine in a rat model of Neuropathic Pain

Neuropathic pain is a chronic pain due to a disorder in the peripheral or central nervous system with different pathophysiological mechanisms. Current treatments are not effective. Here we compared the analgesic effect of nefopam, and morphine in chronic constriction injury [CCI] model of neuropathic pain. Male wistar rat [150-200g, n=8] were divided into 3 different groups: 1- Saline-treated CCI group, 2- Saline-treated sham group, and 3- Drug-treated CCI groups. In CCI model of neuropathic pain, the left sciatic nerve was exposed and 4 loose chromic gut ligatures were placed around the nerve proximal to the trifurcation. Ketamine 60mg/kg and xylazine 10 mg/kg were used for anesthesia. Nefopam [10, 20, 30mg/kg], and morphine [1,3, 5mg/kg] were injected 30 minutes before surgery and continued daily to day 14 post-ligation. Von Frey filaments for mechanical allodynia and acetone test for cold allodynia were respectively used as pain behavioral tests. Experiments were performed on day 0 [before surgery] and days 1, 3, 5,7,10 and 14 post injury. Behavioral studies were performed in a quiet room between 9:00 to 11:00 AM. All experiments followed the IASP guidelines on ethical standards for investigation of experimental pain in animals. Nefopam [20 and 30mg/kg] blocked mechanical and cold allodynia during the experimental period, but the analgesic effects of morphine [5mg/kg] lasted for 7 days. It seems that nefopam could effectively reduce pain behavior compared to morphine with reduced adverse effects. Key Words: neuropathic pain, nefopam, morphine, allodynia

[Effect of oral morphine consumption during pregnancy on the tongue development in the Wistar rat embryos]

Morphine consumption during pregnancy could lead to defect and delay in nervous system development in the embryos. In the present study, development of the tongue of embryos whom their mothers received oral morphine during pregnancy have been studied. Female Wistar rats [200-220 g] after pregnancy were divided randomly into the experimental and control groups. The control group received tap water whereas the experimental group received morphine [0.05 mg/ml] in their drinking waters. On the day 19, the pregnant rats were killed by chloroform overdose and the embryos were removed surgically and were fixed in formalin 10%. Simultaneously, the rats' bloods were collected for corticosterone measurement. Weight and length of the embryos were determined. Then the embryos' heads were removed for tissue processing, cutting and Hematoxylin- Eosin staining. The subjects were evaluated using light microscope and MOTIC software. Number of the cells also counted. Un-paired t-test applied for statistical analysis. Plasma corticosterone level, embryos' weight and length did not show any significant differences between control and experimental groups. The large diameter of the tongue of the experimental group was decreased but the small diameter in two groups did not differ. Tongue cells numbers in the experimental group were increased but their size decreased. Decrease in the large diameter of tongue, increase in the cell number and decrease in cell size indicate the influence of morphine consumption during pregnancy on tongue development in the embryos