buprenorphine and Inflammation

People infected with HIV through injection drug use are more likely to experience progression to AIDS, death due to AIDS, and all-cause mortality even when controlling for access to care and antiretroviral therapy. While high-risk behavior and concurrent infections most certainly are contributors, chronic immune activation, downstream metabolic comorbidities may play an important role.. Altered intestinal integrity plays a major role in HIV-related immune activation and microbial translocation markers are heightened in active heroin users. Additionally, greater injection frequency drives systemic inflammation and is associated with HIV viral rebound. Finally, important systemic inflammation markers have been linked with frailty and mortality in people who inject drugs with and without concurrent HIV infection. Heroin use may work synergistically with HIV infection to cause greater immune activation than either factor alone. Further research is needed to understand the impact on downstream metabolic comorbidities including cardiovascular disease. Medication-assisted treatment for opioid use disorder with methadone or buprenorphine may ameliorate some of this risk; however, there is presently limited research in humans, including in non-HIV populations, describing changes in immune activation on these treatments which is of paramount importance for those with HIV infection.

Topics: Analgesics, Opioid; Buprenorphine; Cardiovascular Diseases; HIV Infections; Humans; Inflammation; Methadone; Opioid Epidemic; Opioid-Related Disorders; Substance Abuse, Intravenous

A model of nociceptive threshold determination was developed for evaluation of NSAID analgesia in cats. In a crossover study, eight cats received carprofen (4 mg/kg), buprenorphine (0.01 mg/kg) or saline (0.3 ml) subcutaneously before intradermal kaolin injection on the antebrachium to induce mild inflammation. Pressure thresholds were measured at the injected site using blunt-ended pins advanced by manual inflation of a bladder within a bracelet. Bladder pressure was recorded as threshold (PT) at the behavioural end point. Baseline PT were recorded before kaolin injection (time 0). PT was measured at 2-10 h intervals for 52 h. PT below the lower 95% confidence interval (CI) of baseline values indicated hyperalgesia. After saline, hyperalgesia was detected from 2-6 h, 22-26 h, and at 30 and 36 h. After carprofen, PT remained within the 95% CI. After buprenorphine, PT remained within the 95% CI except at 2h. Carprofen and to some extent buprenorphine, prevented inflammatory hyperalgesia.

Topics: Animals; Anti-Inflammatory Agents, Non-Steroidal; Buprenorphine; Carbazoles; Cat Diseases; Cats; Cross-Over Studies; Female; Hyperalgesia; Inflammation; Male; Pain

This study aimed to investigate how opioids affect phagocytosis and microglial nitrite and nitric oxide synthase (iNOS) production during inflammation.. Opioids are a group of chemicals that are naturally found in the opium poppy plant and exert a variety of effects on the brain, including pain alleviation in some cases. They are commonly used in surgery and perioperative analgesia. However, research on the impact of opioids on microglial inflammatory factor production and phagocytosis is limited.. This study was designed to investigate the effects of opioids on inducible nitric oxide synthase (iNOS) activity and nitric oxide (NO) generation. Moreover, the influence of opioids on the engulfment of C8-B4 microglial cells after stimulation with LPS was also examined.. C8-B4 mouse microglial cells were exposed to various concentrations of opioids after stimulation with lipopolysaccharide (LPS) and interferon-γ (IFN-γ). Nitrite production was assayed. The iNOS and Cox-2 were determined by Western blotting, and fluorescent immunostaining was performed to assess the percentage of microglia that engulfed fluorescent microspheres in total microglia cultivating with opioids after being activated by LPS.. After LPS and IFN-γ stimulation, microglia produced lower amounts of nitric oxide (NO) production with buprenorphine, salvinorin A, and naloxone (P<0.05). When combined with naloxone, no significant differences were found than buprenorphine. It was observed that buprenorphine and salvinorin A could suppress iNOS expression activated by LPS and IFN-γ. Phagocytosis was greatly increased after LPS stimulation, and a significant increase was observed after adding salvinorin A.. Buprenorphine and salvinorin A were found to reduce NO production and iNOS induction in microglial cells activated by LPS and IFN-γ. Salvinorin A promoted the phagocytosis of microglia cells treated by LPS.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Inflammation; Interferon-gamma; Lipopolysaccharides; Mice; Microglia; Naloxone; Nitric Oxide; Nitric Oxide Synthase; Nitric Oxide Synthase Type II; Nitrites; Phagocytosis

Traumatic brain injury (TBI) is the leading cause of death, disability, and mental health disorders. A wide range of bioactive lipids, cytokines, and chemokines drives the inflammatory response. This study aimed to assess the efficacy of buprenorphine on moderate Trauma Brain Injury (mTBI) in rats.. In this study, 21 Wistar male rats weighing 230 ± 10 g were included. We trained cases by Morris water navigation task and mTBI induced by the pendulum. Then, buprenorphine treatment with 0.05 mg per kilogram of body weight continued from day 8 to 21. Finally, by Micro-Computed Tomography, behavioral evaluation by the Morris aqueous riddle test and biochemical factors of inflammation were assessed.. Severe subdural inflammation was more in the treatment group than in the control group. The behavior of Rats showed that in the buprenorphine group, the mean duration of finding the platform increased compared to the control and Sham groups. However, the groups had no significant differences (. These results suggest that buprenorphine causes fewer changes in behavioral functions in rats' models of mTBI and, because of their positive effect changes on inflammation biomarkers, biochemical behavioral tests, and CT scan images, could be ideal analgesic agents for pre-clinical responses after TBI.

Topics: Animals; Brain Injuries, Traumatic; Buprenorphine; Disease Models, Animal; Inflammation; Male; Rats; Rats, Wistar; X-Ray Microtomography

Approximately 15-40% of people living with HIV develop HIV-associated neurocognitive disorders, HAND, despite successful antiretroviral therapy. There are no therapies to treat these disorders. HIV enters the CNS early after infection, in part by transmigration of infected monocytes. Currently, there is a major opioid epidemic in the United States. Opioid use disorder in the context of HIV infection is important because studies show that opioids exacerbate HIV-mediated neuroinflammation that may contribute to more severe cognitive deficits. Buprenorphine is an opioid derivate commonly prescribed for opiate agonist treatment. We used the EcoHIV mouse model to study the effects of buprenorphine on cognitive impairment and to correlate these with monocyte migration into the CNS. We show that buprenorphine treatment prior to mouse EcoHIV infection prevents the development of cognitive impairment, in part, by decreased accumulation of monocytes in the brain. We propose that buprenorphine has a novel therapeutic benefit of limiting the development of neurocognitive impairment in HIV-infected opioid abusers as well as in nonabusers, in addition to decreasing the use of harmful opioids. Buprenorphine may also be used in combination with HIV prevention strategies such as pre-exposure prophylaxis because of its safety profile.

Topics: AIDS Dementia Complex; Animals; Antigens, Ly; Brain; Buprenorphine; Chronic Disease; Cognitive Dysfunction; Disease Models, Animal; HIV Infections; Inflammation; Male; Mice, Inbred C57BL; Monocytes; Phenotype; Viral Load

Buprenorphine (BUP), a "synthetic derivative of the opioid alkaloid thebaine", may be associated with cellular damage in the central nervous system.. This study was designed to investigate the effects of low and high doses of BUP on oxidative and inflammatory indices in the hippocampus and learning and memory behavior in an animal model.. The association between BUP administration and oxidative and inflammatory damage and also learning and memory impairment is not clear.. For this reason, twenty-four male Wistar rats were randomly allocated into one control and two BUP-treated groups (0.3 and 1 mg/kg, SC), (n=8, for each group). After 4 weeks, learning and memory abilities were assessed by using Y-maze test. Then, oxidative stress indices including glutathione (GSH), malondialdehyde (MDA), superoxide dismutase (SOD), glutathione peroxidase (GPx) and catalase (CAT) were assessed in the serum and hippocampus of each animal by using spectrophotometer. Inflammatory parameters such as tumor necrotic factor-α (TNF-α), interleukin- 6 (IL-6), and interleukin-1β (IL-1β) were also measured in the serum and hippocampus of rats by using ELISA.. The present findings indicated that the memory and learning time was lengthened in BUP (1mg/kg)-treated rats versus control animals (p<0.05). Additionally, it was observed that BUP (1 mg/kg) significantly increased the serum and hippocampal levels of MDA and TNF-α and also decreased GSH levels versus the control group (p< 0.05).. The results of the present study revealed that BUP may cause learning and memory dysfunction by inducing oxidative stress and inflammation in the hippocampus.

Topics: Animals; Buprenorphine; Hippocampus; Inflammation; Male; Maze Learning; Memory; Oxidative Stress; Rats; Rats, Wistar

The urgent need for more effective analgesic treatment options has prompted a re-evaluation of the behavioral tests used to assess pain in pre-clinical research, with an emphasis on inclusion of more voluntary, un-evoked behavioral assessments of pain. In order to validate voluntary gait analysis and a voluntary mechanical conflict-avoidance assay, we tested mouse models of neuropathy (spared nerve injury) and inflammation (complete Freund's adjuvant) alongside reflexive measures of mechanical and thermal hypersensitivity. To establish whether the observed changes in behavioral responses were pain-related, known analgesics (buprenorphine, gabapentin, carprofen) were also administered. Spared nerve injury persistently altered several gait indices, whereas complete Freund's adjuvant caused only transient changes. Furthermore, known analgesics could not reverse these gait changes, despite demonstrating their previously established efficacy in reflexive measures of mechanical and thermal hypersensitivity. In contrast, the mechanical conflict-avoidance assay demonstrated aversion in mice with neuropathy and inflammation-induced hypersensitivity, which could both be reversed by analgesics. We conclude that voluntary gait changes in rodent neuropathic and inflammatory pain models are not necessarily indicative of pain-related adaptations. On the other hand, mechanical conflict-avoidance represents a valid operant assay for quantifying pain-related behaviors in mice that can be reversed by known analgesics.

Topics: Analgesics; Animals; Buprenorphine; Carbazoles; Disease Models, Animal; Female; Freund's Adjuvant; Gabapentin; Gait; Inflammation; Male; Mice; Mice, Inbred C57BL; Neuralgia; Pain Measurement

HIV infection of the CNS causes neuroinflammation and damage that contributes to the development of HIV-associated neurocognitive disorders (HAND) in greater than 50% of HIV-infected individuals, despite antiretroviral therapy (ART). Opioid abuse is a major risk factor for HIV infection. It has been shown that opioids can contribute to increased HIV CNS pathogenesis, in part, by modulating the function of immune cells. HIV enters the CNS within two weeks after peripheral infection by transmigration of infected monocytes across the blood brain barrier (BBB). CD14

Topics: AIDS Dementia Complex; Buprenorphine; Cell Adhesion; Cells, Cultured; Chemokine CCL2; Chemotaxis, Leukocyte; GPI-Linked Proteins; Humans; Inflammation; Intercellular Adhesion Molecule-1; Lipopolysaccharide Receptors; Monocytes; Nuclear Pore Complex Proteins; Opioid-Related Disorders; Receptors, IgG; Receptors, Opioid, kappa; Receptors, Opioid, mu; THP-1 Cells; Transendothelial and Transepithelial Migration; Vascular Cell Adhesion Molecule-1

Mouse models of inflammatory bowel disease (IBD) identify an impact on the enteric nervous system (ENS) but do not distinguish between Crohn's disease and ulcerative colitis phenotypes. In these models, analgesia is required, but its influence on different strains and disease outcomes is unknown. Therefore, changes to the ENS and intestinal smooth muscle were studied in trinitrobenzene sulfonic acid (TNBS) and dextran sodium sulfate (DSS) induced colitis to identify the effects of analgesia, and compared between two mouse strains.. Colitis was induced in CD1 or BALB/c mice receiving analgesia with either buprenorphine or tramadol. Euthanasia was on Day 8 (DSS) or Day 4 (TNBS). Outcomes were Disease Activity Index and cytokine assay, and quantitative histology and immunocytochemistry were used to evaluate effects of inflammation on neurons and smooth muscle.. In BALB/c mice, both models of colitis caused >2-fold increase in smooth muscle cell number. DSS caused axon proliferation without neuron loss while TNBS caused significant neuron loss and axonal damage. Buprenorphine (but not tramadol) was generally anti-inflammatory in both strains, but correlated with lethal outcomes to TNBS in BALB/c mice.. Smooth muscle growth is common to both models of colitis. In contrast, ENS damage in TNBS is correlated with the severe response of a Crohn's disease-like phenotype, while DSS correlates with a milder, ulcerative colitis-like outcome in the deeper tissues. Analgesia with tramadol over buprenorphine is supported for mouse studies of IBD.

Topics: Analgesia; Analgesics, Opioid; Animals; Buprenorphine; Colitis; Dextran Sulfate; Disease Models, Animal; Inflammation; Intestines; Mice; Mice, Inbred BALB C; Tramadol; Trinitrobenzenesulfonic Acid

Buprenorphine is recommended for use as an analgesic in animal models including in murine models of collagen-induced arthritis (CIA). However, the effect of buprenorphine on the expression of disease-associated biomarkers is not well defined. We examined the effect of buprenorphine administration on disease progression and the expression of inflammatory and oxidative stress markers, in a murine model of CIA. Buprenorphine administration altered the expression of cytokines, IFN-

Topics: Adult; Aged; Analgesics, Opioid; Animals; Antioxidants; Arthritis, Experimental; Arthritis, Rheumatoid; Biomarkers; Buprenorphine; Catalase; Cohort Studies; Collagen; Cytokines; Disease Models, Animal; Disease Progression; Female; Humans; Inflammation; Male; Matrix Metalloproteinase 3; Mice; Mice, Inbred DBA; Middle Aged; Nitric Oxide Synthase Type II; Oxidative Stress; Real-Time Polymerase Chain Reaction; Superoxide Dismutase-1

Topics: Analgesics, Opioid; Animals; Buprenorphine; Depression; Disease Models, Animal; Dose-Response Relationship, Drug; Female; Freund's Adjuvant; Hyperalgesia; Inflammation; Male; Nociception; Pain; Pain Measurement; Pain Threshold; Rats; Rats, Sprague-Dawley; Recovery of Function; Running; Sex Factors

Postoperative cognitive dysfunction (POCD) often occurs in elderly patients and may involve neuroinflammation. This study was to determine whether anesthetic choice (intravenous vs. volatile anesthetics) affects cognitive impairment and neuroinflammation in elderly rat. Total 54 twenty-month old male Fischer 344 rats were assigned randomly to control, right carotid exposure under propofol-buprenorphine or isoflurane-buprenorphine anesthesia groups. They were tested by Barnes maze and fear conditioning from 6 days after the surgery. Their brains were harvested 24 h after the surgery for quantifying interleukin (IL) 1β, tumor necrosis factor (TNF)α and ionized calcium binding adaptor molecule 1 (Iba-1). We showed that the heart rates and mean arterial blood pressure were similar during surgery under propofol-buprenorphine or isoflurane-buprenorphine anesthesia. There was no difference in the surgery-induced increase of the plasma IL-1β and TNFα levels under these two types of anesthesia. Rats subjected to surgery took longer than control rats to identify the target hole 8 days after the completion of training sessions in Barnes maze [32 ± 23 s for control, 118 ± 64 s for propofol group (P < 0.05 vs. control), 107 ± 64 s for isoflurane group (P < 0.05 vs. control)] and had less freezing behavior in the fear conditioning test. Surgery and anesthesia increased IL-1β and Iba-1 but did not affect tau phosphorylated at S199/202 and S396 in the cerebral cortex and hippocampus. Our results suggest that surgery under general anesthesia induces neuroinflammation and cognitive impairment. Anesthetic choice may not be a significant modifiable factor for these effects.

Topics: Anesthetics, General; Anesthetics, Inhalation; Anesthetics, Intravenous; Animals; Buprenorphine; Calcium-Binding Proteins; Fear; Inflammation; Interleukin-1beta; Isoflurane; Learning Disabilities; Male; Maze Learning; Memory Disorders; Microfilament Proteins; Postoperative Complications; Propofol; Rats; Rats, Inbred F344; Tumor Necrosis Factor-alpha

Venous thrombosis (VT) is a significant cause of morbidity and mortality in humans. Surgical animal models are crucial in studies investigating the pathogenesis of this disease and evaluating VT therapies. Because inflammation is critical to both the development and resolution of VT, analgesic medications have the potential to adversely affect multiple parameters of interest in VT research. The objective of this study was to determine how several common analgesics affect key variables in a murine ligation model of deep vein thrombosis. Male C57BL/6 mice were randomly assigned to receive either local (bupivacaine) or systemic parenteral analgesia (buprenorphine, tramadol, or carprofen) or 0.9% NaCl (control). All mice underwent laparotomy and ligation of the inferior vena cava, and treatment was continued until euthanasia at 6 or 48 h after surgery. Analysis of harvested tissues and blood included: hematology, thrombus weight, serum and vein-wall cytokines (IL1β, IL6, IL10, TNFα), soluble P-selectin, and vein-wall leukocyte infiltration. Compared with 0.9% NaCl, all of the analgesics affected multiple parameters important to VT research. Carprofen and tramadol affected the most parameters and should not be used in murine models of VT. Although they affected fewer parameters, a single dose of bupivacaine increased thrombus weight at 6 h, and buprenorphine was associated with reduced vein wall macrophages at 48 h. Although we cannot recommend the use of any of the evaluated analgesic dosages in this mouse model of VT, buprenorphine merits additional investigation to ensure the highest level of laboratory animal care and welfare.

Topics: Analgesics; Anesthetics, Local; Animals; Bupivacaine; Buprenorphine; Carbazoles; Disease Models, Animal; Inflammation; Ligation; Male; Mice; Mice, Inbred C57BL; Random Allocation; Tramadol; Vena Cava, Inferior; Venous Thrombosis

The aim of this study is to investigate the effect of general anaesthesia induced by isoflurane with buprenorphine on hippocampus-dependent and neocortex-dependent memory, respectively, in mice, and in addition, to compare the effects of such anaesthesia on these memory processes with the effects induced by lipopolysaccharide (LPS) administration on the same memory processes.. To assess hippocampus-dependent memory, isoflurane (for 15 min) after buprenorphine injection, or LPS 100 μg/kg (intraperitoneally) was administered 24 h before or after fear conditioning. The effect of these treatments on hippocampus-dependent memory was assessed using contextual fear-conditioning tasks at day 4. To assess neocortex-dependent memory, isoflurane anaesthesia or LPS was given 72 h after contextual fear conditioning. Neocortex-dependent memory assessment was performed at day 32.. Unlike LPS injection, isoflurane with buprenorphine-induced anaesthesia does not impair freezing responses in hippocampus-dependent fear-conditioning memory tasks. On anterograde amnesia assessment: 49.67 ± 6.87% for the anaesthesia group and 54.5 ± 4.12% for the control group. On retrograde amnesia assessment: 47.16 ± 8.71% for the anaesthesia group and 54.5 ± 4.12% for control group; P > 0.05. Thus, neither isoflurane nor buprenorphine impair hippocampus-dependent memory. However, on the neocortex-dependent memory task, both isoflurane-induced anaesthesia and LPS-induced inflammation result in reduced freezing responses: 62.13 ± 5.80% for the anaesthesia group, 74.63 ± 5.69% for the LPS group, and 81.75 ± 3.26% for the control group; P < 0.05 compared with control group.. General anaesthesia induced by isoflurane with buprenorphine may result in impairment of neocortex-dependent memory in mouse. However, general anaesthesia so induced does not impair hippocampus-dependent memory in mouse in our experimental conditions.

Topics: Amnesia; Anesthetics, Inhalation; Animals; Behavior, Animal; Buprenorphine; Conditioning, Operant; Electroshock; Fear; Hippocampus; Inflammation; Isoflurane; Lipopolysaccharides; Male; Memory Disorders; Mice; Mice, Inbred C57BL; Narcotics; Neocortex

To test the reliability and validity of a novel rat-holding device designed to be used in conjunction with the plantar test apparatus for studying nocifensive behavioral responses in an established model of temporomandibular joint (TMJ) pathology.. Thirty-five young adult male Sprague-Dawley rats were used. Withdrawal latencies in response to infrared 40 heat stimulation of the submandibular region in naïve animals (n = 4) and animals injected with saline or complete Freund's adjuvant (CFA) in the TMJ (n > 9) were measured over a 2-week time period. Nocifensive responses to mechanical stimulation of the cutaneous tissue directly over the TMJ with von Frey filaments were investigated in animals injected with CFA in the TMJ (n = 6). The effect on nocifensive responses to heat and mechanical stimulation of subcutaneous administration of buprenorphine (0.05 mg/kg) into the hindquarter was assessed in CFA and cotreated animals (n = 6). Statistical analysis was performed using a nonparametric Mann-Whitney U test.. Under basal conditions, withdrawal latencies to heat stimulation of the orofacial region remained consistently around 15 seconds over 14 days. Unilateral CFA injection in the TMJ significantly decreased heat-withdrawal latencies on days 1, 2, 7, and 14 in the ipsilateral side (P < .05), but not contralateral side, when compared with basal values. CFA also significantly decreased the nocifensive threshold to mechanical stimulation on days 1, 2, and 7 postinjection (P < .05). CFA-mediated changes in heat withdrawal and mechanical thresholds in the orofacial region were significantly suppressed by subcutaneous administration of buprenorphine into the hindquarter (P < .05).. Findings from this study provide evidence to validate the use of this holding device for studying nocifensive behaviors in the orofacial region of rats in response to heat or mechanical orofacial stimulation.

Topics: Analgesics, Opioid; Animals; Avoidance Learning; Behavior, Animal; Buprenorphine; Facial Pain; Freund's Adjuvant; Head Movements; Hot Temperature; Inflammation; Male; Neck; Physical Stimulation; Rats; Rats, Sprague-Dawley; Reaction Time; Restraint, Physical; Temporomandibular Joint; Trigeminal Nerve

Anesthetics used in burn and trauma animal models may be influencing results by modulating inflammatory and acute-phase responses. Accordingly, we determined the effects of various anesthetics, analgesia, and euthanasia techniques in a rodent burn model. Isoflurane (ISO), ketamine-xylazine (KX), or pentobarbital (PEN) with or without buprenorphine were administered before scald-burn in 72 rats that were euthanized without anesthesia by decapitation after 24 h and compared with unburned shams. In a second experiment, 120 rats underwent the same scald-burn injury using KX, and 24 h later were euthanized under anesthesia or carbon dioxide (CO2). In addition, we compared euthanasia by exsanguination with that of decapitation. Serum cytokine levels were determined by an enzyme-linked immunosorbent assay. In the first experiment, ISO was associated with elevation of cytokine-induced neutrophil chemoattractant 2 (CINC-2) and monocyte chemotactic protein 1 (MCP-1), and KX and PEN was associated with elevation of CINC-1,CINC-2, IL-6, and MCP-1. Pentobarbital also decreased IL-1". IL-6 increased significantly when ISO or PEN were combined with buprenorphine. In the second experiment, euthanasia performed by exsanguination under ISO was associated with reduced levels of IL-1", CINC-1, CINC-2, and MCP-1, whereas KX reduced CINC-2 and increased IL-6 levels. Meanwhile, PEN reduced levels of IL-1" and MCP-1, and CO2 reduced CINC-2 and MCP-1. In addition,decapitation after KX, PEN, or CO2 decreased IL-1" and MCP-1, although we found no significant difference between ISO and controls. Euthanasia by exsanguination compared with decapitation using the same agent also led to modulation of several cytokines. Differential expression of inflammatory markers with the use of anesthetics and analgesics should be considered when designing animal studies and interpreting results because these seem to have a significant modulating impact. Our findings indicate that brief anesthesia with ISO immediately before euthanasia by decapitation exerted the least dampening effect on the cytokines measured. Conversely, KX with buprenorphine may offer a better balance during longer procedures to avoid significant modulation. Standardization across all experiments that are compared and awareness of these findings are essential for those investigating the pathophysiology of inflammation in animal models.

Topics: Acute-Phase Reaction; Analgesia; Analgesics; Anesthesia, General; Anesthetics; Animals; Buprenorphine; Burns; Carbon Dioxide; Cytokines; Decapitation; Euthanasia, Animal; Inflammation; Isoflurane; Ketamine; Male; Models, Animal; Pentobarbital; Random Allocation; Rats; Rats, Sprague-Dawley; Shock, Hemorrhagic; Xylazine

The purposes of this study were to determine 1) whether magnetic resonance imaging (MRI)-based T2 mapping and measurements of limb volume can differentiate injured and uninjured tissue after blunt trauma to rat hindlimbs and 2) whether administration of buprenorphine influences these assessments. Male Wistar rats (age, 3 to 4 mo) underwent blunt contusion injury to the posterior aspect of the hindlimb; MRI was conducted at 6, 12, 24, 48, 72, and 96 h after injury. The imaging results showed that administration of buprenorphine had no effect on the T2 value {area under the receiver operating characteristic [ROC] curve: with drug, 0.869 [95% confidence interval (CI), 0.78 to 0.96]; without drug, 0.809 [95% CI, 0.72 to 0.90]} but did influence limb volume [area under the ROC curve; without drug, 0.954 (95% CI, 0.92 to 0.99); with drug, 0.713 (95% CI, 0.61 to 0.82)]. When using MRI to determine the extent of injury or to track injury over time, calculated limb volumes may lose sensitivity to detect injury, due to the intrinsic increase in volume from morphine-derived drugs. During administration of morphine derivatives, T2 maps may provide more accurate assessments of muscle tissue injury both initially after injury and over time.

Topics: Analgesics, Opioid; Animals; Buprenorphine; Disease Models, Animal; Edema; Hemorrhage; Hindlimb; Inflammation; Magnetic Resonance Imaging; Male; Predictive Value of Tests; Rats; Rats, Wistar; ROC Curve

Hyperpolarization-activated cyclic nucleotide-gated (HCN) channels are active at resting membrane potential and thus contribute to neuronal excitability. Their increased activity has recently been demonstrated in models of nerve injury-induced pain. The major aim of the current study was to investigate altered HCN channel protein expression in trigeminal sensory neurons following inflammation of the dura. HCN1 and HCN2 channel immunoreactivity was observed on the membranes of medium- to large-sized trigeminal ganglion neurons with 76% and 85% of HCN1 and HCN2 expressing neurons also containing the 200 kDa neurofilament protein (associated with myelinated fibers). Western immunoblots of lysates from rat trigeminal ganglia also showed bands with appropriate molecular weights for HCN1 and HCN2. Three days after application of complete Freund's adjuvant (CFA) to the dura mater, Western blot band densities were significantly increased; compared to control, to 166% for HCN1 and 284% for HCN2 channel protein. The band densities were normalized against alpha-actin. In addition, the number of retrogradely labeled neurons from the dura expressing HCN1 and HCN2 was significantly increased to 247% (HCN1) and 171% (HCN2), three days after inflammation. When the opioid receptor partial agonist, buprenorphine, was given systemically, immediately after CFA, the inflammation-induced increase in HCN protein expression in both Western blot and immunohistochemical experiments was not observed. These results suggest that HCN1 and HCN2 are involved in inflammation-induced sensory neuron hyperexcitability, and indicate that an opioid receptor agonist can reverse the protein upregulation.

Topics: Analgesics, Opioid; Animals; Brain; Buprenorphine; Cyclic Nucleotide-Gated Cation Channels; Dura Mater; Freund's Adjuvant; Hyperpolarization-Activated Cyclic Nucleotide-Gated Channels; Inflammation; Ion Channel Gating; Ion Channels; Male; Neurofilament Proteins; Neurons; Potassium Channels; Rats; Rats, Sprague-Dawley; Receptors, Opioid; Trigeminal Ganglion

Opioids mediate their analgesic effects by activating mu-opioid receptors (MOR) not only within the central nervous system but also on peripheral sensory neurons. The peripheral analgesic effects of opioids are best described under inflammatory conditions (e.g., arthritis). The present study investigated the effects of inflammation on MOR binding and G-protein coupling of full versus partial MOR agonists in dorsal root ganglia (DRG) of primary afferent neurons. Our results show that Freund's complete adjuvant (FCA) unilateral hindpaw inflammation induces a significant up-regulation of MOR binding sites (25 to 47 fmol/mg of protein) on DRG membranes without affecting the affinity of either full or partial MOR agonists. In our immunohistochemical studies, the number of MOR-immunoreactive neurons consistently increased. This increase was mostly caused by small-diameter nociceptive DRG neurons. The full agonist DAMGO induced MOR G-protein coupling in DRG of animals without FCA inflammation (EC50 = 56 nM; relative Emax = 100%). FCA inflammation resulted in significant increases in DAMGO-induced MOR G-protein coupling (EC50 = 29 nM; relative Emax = 145%). The partial agonist buprenorphine hydrochloride (BUP) showed no detectable G-protein coupling in DRG of animals without FCA inflammation; however, partial agonist activity of BUP-induced MOR G-protein coupling was detectable in animals with FCA inflammation (EC50 = 1.6 nM; relative Emax = 82%). In behavioral studies, administration of BUP produced significant antinociception only in inflamed but not in noninflamed paws. These findings show that inflammation causes changes in MOR binding and G-protein coupling in primary afferent neurons. They further underscore the important differences in clinical studies testing peripherally active opioids in inflammatory painful conditions.

Topics: Animals; Behavior, Animal; Binding Sites; Buprenorphine; Enkephalin, Ala(2)-MePhe(4)-Gly(5)-; Ganglia, Spinal; GTP-Binding Proteins; Guanosine 5'-O-(3-Thiotriphosphate); Immunohistochemistry; Inflammation; Male; Neurons, Afferent; Pain; Rats; Rats, Wistar; Receptors, Opioid, mu; Sciatic Nerve; Sulfur Radioisotopes

To assess the effect on tracheal graft preservation of perfusion of donor tissue with a Collins solution before extraction and immunosuppression of the recipient. An experimental study was performed in 36 albino rabbits with revascularized heterotopic cervical reconstruction of the trachea with omentum. The animals were distributed in four groups. Groups I (n = 9) and III (n = 9) were transplanted with non perfused donor tissue. Animals in groups II (n = 9) and IV (n = 9) received grafts perfused with Collins solution. Immunosuppression with steroids and cyclosporin was continued for 21 days in groups III and IV. In a mid portion of the trachea viewed under optical microscope, the degree of inflammation or circumferential necrosis was assessed on a scale of 0 to 9 by adding the scores for mucosa, submucosa and cartilage. The mean score for tracheal lesion was lower in group IV, with a likelihood of random difference of less than 5%. Perfusion of peritracheal tissues with Collins solution in the donor, in addition to immunosuppression decreases the extent of tissue damage in the tracheal graft.

Topics: Analgesics, Opioid; Animals; Anti-Inflammatory Agents; Buprenorphine; Cefazolin; Cephalosporins; Cyclosporins; Data Interpretation, Statistical; Female; Hypertonic Solutions; Immunosuppression Therapy; Immunosuppressive Agents; Inflammation; Male; Methylprednisolone; Necrosis; Perfusion; Rabbits; Time Factors; Tissue Donors; Trachea