Carbamazepine effects on pain management and serum IL-6, IL-10 evaluation in addicted patients undergoing surgery.

Postoperative pain control remains an important issue in the field of surgery. Assessing and managing patients with acute pain who are addicted to opioids are often challenging. It has been shown that, addicted patients are less tolerant to pain. There is limited evidence to guide the management of acute pain in these patients. Here we studied the effect of preemptive use of carbamazepine on pain behavior and serum IL-6, IL-10 levels in the addicted patients. 90 male patients (25-45 years, BMI 20-27), were divided into 3 group of 30 patients: 1- control, 2- addicted, 3- addicted patients receiving carbamazepine 400mg before surgery. The visual analog pain scale and serum levels of IL-6 and IL-10 were evaluated at time 0 (before surgery), 1 and 12h postoperatively. Compared with control and carbamazepine groups, addicted patients exhibited exaggerated pain behavior before and after surgery, however, postoperatively, a significant increase in pain behavior was seen in control compared to carbamazepine group. A decrease in serum IL-10 and an increase in IL-6 concentrations were observed in addicted patients. In the morphine abuser, a decrease in pain threshold, an increase in IL-6 and a decrease in IL-10 levels were evident compared with non-abuser subjects. Addition of carbamazepine improved pain sensation and serum IL-6 levels and a reduction in serum IL-10 level in control patients was paralleled to their recovery. It seems that, preemptive use of low dose of carbamazepine can improve postoperative pain and cytokine activities in the addicted patients.

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.

Immunomodulatory activities of chitin microparticles on Leishmania major-infected murine macrophages.

BACKGROUND: Chitin microparticles (CMPs) are found to be potent macrophage stimulators; however, their immunomodulatory effects on the parasite-infected macrophages have not yet been studied. To address this issue, we used a Leishmania major-infected murine macrophage model and characterized the regulatory effects of CMPs on the parasite-infected cells. METHODS: Mouse peritoneal macrophages were prepared and infected with L. major (MRHO/IR/1975/ER) standard strain. Following cell treatment with CMPs (500 µg/mL) for 48 h, percent of infected macrophages was determined by Giemsa staining and compared with untreated cells. To find the potential mechanisms of the activity of CMPs, TNF-α and accumulated nitrite in the culture supernatants of the treated and untreated cells were also measured by ELISA and colorimetric Griess assays, respectively. RESULTS: According to the obtained results, chitin microparticles reduced the ex vivo parasite infectivity by ∼12%. However, this inhibitory effect was not directly related to the increased biosynthesis and release of nitric oxide (NO) by macrophages. Instead, we observed a significant increase in the level of TNF-α secretion due to cell treatment with CMPs. Interestingly, this overexpression of TNF-α did not impair cell viability, suggesting the anti-apoptotic effects of the CMPs. CONCLUSIONS: These findings show that chitin microparticles have immunomodulatory effects on L. major-infected macrophages and further provide motivations for future studies on their in vivo effects.

The attenuation of pain behaviour and serum interleukin-6 concentration by nimesulide in a rat model of neuropathic pain.

Background Evidence for a role of immune system in hyperalgesic pain states is increasing. Recent work in neuroimmunology suggests that the immune system does more than simply perform its well known functions of recognizing and removing invading pathogens and tumors. Interest in neuroinflammation and neuroimmune activation has grown rapidly in recent years with the recognition of the role of central nervous system inflammatiom and immune responses in the aetiology of pain states. Among various theories, the role of inflammatory responses of the injured nerve has recently received attention. Cytokines are heterogenous group of polypeptides that activate the immune system and mediate inflammatory responses, acting on a variety of tissue, including the peripheral and central nervous system. Interleukin-6 (IL-6) a pro-inflammatory cytokine, is potentially important in pain aetiology, have pronociceptive actions. Neuropathic pain may be due to a primary insult to the peripheral or central nervous system. Substances released during inflammation from immune cells play an important role in the development and maintenance of chronic pain. Nimesulide, a highly selective cox-2 inhibitor, effectively reduces hyperalgesia due to peripherally administration of inflammatory agents like formalin. The safety of nimesulide was reported for some conditions in which other NSAIDs are contraindicated. Here we have determined the effect of nimesulide on pain behaviour and serum IL-6 level in chronic constriction injury (CCI) model of neuropathic pain. Methods Experiments were carried out on male Wistar rats, (weight 150-200 g, n = 8). Rats were divided into 3 different groups: 1-CCI + saline 0.9% 2Sham + saline 0.9% (control) 3CCI + drug. Nimesulide (1.25, 2.5, 5 mg/kg, i.p.) was injected 1h before surgery and continued daily to day 14 post-ligation. 42 °C water for thermal hyperalgesia, von Frey filaments for mechanical allodynia, acetone test for cool allodynia and 10 °C water for cold hyperalgesia were respectively used as pain behavioural tests. Behavioural tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 10, 14 and the serum concentration of IL-6 was determined at the day 14. Results The results of this study showed a decrease in hyperalgesia and allodynia following nimesulide administration. Conclusions It appears that nimesulide was able to reduce pain behaviour due to nerve inflammation and a parallel decrease in the serum IL-6 concentration was observed. Implications The immune system is an important mediator in the cascade of events that ultimately results in hyperalgesia. Cytokines contribute to the patheogenesis of neuropathic pain, therefore drugs that inhibit cytokine release from immune cells may reduce inflammatory pain states.

Suppression of interleukin-6 by minocycline in a rat model of neuropathic pain.

Inflammatory mediators produced in the injured nerve have been proposed as contributing factors in the development of neuropathic pain. In this regard an important role is assigned to interleukin-6. The present study, evaluated the effect of pretreatment with minocycline, on pain behavior (hyperalgesia and allodynia) and serum level of interleukin-6 in chronic constriction injury (CCI) model of neuropathic pain in rat. Minocycline (5, 10, 20 and 40 mg/kg, i.p.) was injected 1 h before surgery and continued daily to day 14 post-ligation. Behavioral tests were recorded before surgery and on postoperative days 1, 3, 5, 7, 9, 10, 14, and the serum concentration of interleukin-6 was determined at day 14. We observed that minocycline which was reported to have a neuroprotective effect in some neurodegenerative diseases, reversed hyperalgesia and allodynia due to sciatic nerve ligation and inhibited the interleukin-6 production. It seems that minocycline could have an anti-inflammatory and analgesic effect in some chronic pain states.