The pro-resolving lipid mediator Maresin 1 ameliorates pain responses and neuroinflammation in the spared nerve injury-induced neuropathic pain: A study in male and female mice.

Specialized pro-resolving mediators (SPMs) have recently emerged as promising therapeutic approaches for neuropathic pain (NP). We evaluated the effects of oral treatment with the SPM Maresin 1 (MaR1) on behavioral pain responses and spinal neuroinflammation in male and female C57BL/6J mice with spared nerve injury (SNI)-induced NP. MaR1, or vehicle, was administered once daily, on post-surgical days 3 to 5, by voluntary oral intake.

Effects of NADPH Oxidase Isoform-2 (NOX2) Inhibition on Behavioral Responses and Neuroinflammation in a Mouse Model of Neuropathic Pain.

NADPH oxidase isoform-2 (NOX2) has been implicated in the pathophysiology of neuropathic pain (NP), mostly through the modulation of neuroinflammation. Since it is also accepted that some neuroimmune mechanisms underlying NP are sex-dependent, we aimed to evaluate the effects of early systemic treatment with the NOX2-selective inhibitor (NOX2i) GSK2795039 on behavioral responses and spinal neuroinflammation in spared nerve injury (SNI)-induced NP in male and female mice. Mechanical sensitivity was evaluated with the von Frey test, while general well-being and anxiety-like behavior were assessed with burrowing and light/dark box tests.

Neuroinflammation, oxidative stress and their interplay in neuropathic pain: Focus on specialized pro-resolving mediators and NADPH oxidase inhibitors as potential therapeutic strategies.

Neuropathic pain (NP) is a chronic condition that results from a lesion or disease of the nervous system, greatly impacting patients' quality of life. Current pharmacotherapy options deliver inadequate and/or insufficient responses and thus a significant unmet clinical need remains for alternative treatments in NP. Neuroinflammation, oxidative stress and their reciprocal relationship are critically involved in NP pathophysiology.

An alternative method for oral drug administration by voluntary intake in male and female mice.

Drug administration to experimental rodents is often invasive and stressful, thus reducing animal welfare and potentially confounding experimental results. Methods of oral drug delivery in which rodents cooperate voluntarily minimize stress, pain and morbidity. We herein describe a method for oral administration through voluntary intake of strawberry jam, developed for C57BL/6J mice.

l-proline supplementation improves nitric oxide bioavailability and counteracts the blood pressure rise induced by angiotensin II in rats.

We evaluated whether l-proline (Pro) supplementation improves redox status and nitric oxide (NO) bioavailability and prevents or delays angiotensin II (AngII)-induced hypertension. Male Sprague-Dawley rats were distributed to four experimental groups: Pro + AngII (Pro-Ang), Pro + Saline (Pro-Sal), Vehicle + AngII (Veh-Ang) and Veh + Saline (Veh-Sal). Pro solution (2 g.

Morphine glucuronidation increases its analgesic effect in guinea pigs.

Aims: Morphine is extensively metabolized to neurotoxic morphine-3-glucuronide (M3G) and opioid agonist morphine-6-glucuronide (M6G). Due to these different roles, interindividual variability and co-administration of drugs that interfere with metabolism may affect analgesia. The aim of the study was to investigate the repercussions of administration of an inducer (2,3,7,8-tetrachlorodibenzo-p-dioxin, TCDD) and an inhibitor (ranitidine) of glucuronidation in morphine metabolism and consequent analgesia, using the Guinea pig as a suitable model.

Angiotensin II contributes to glomerular hyperfiltration in diabetic rats independently of adenosine type I receptors.

Increased angiotensin II (ANG II) or adenosine can potentiate each other in the regulation of renal hemodynamics and tubular function. Diabetes is characterized by hyperfiltration, yet the roles of ANG II and adenosine receptors for controlling baseline renal blood flow (RBF) or tubular Na(+) handling in diabetes is presently unknown. Accordingly, the changes in their functions were investigated in control and 2-wk streptozotocin-diabetic rats after intrarenal infusion of the ANG II AT1 receptor antagonist candesartan, the adenosine A1 receptor antagonist 8-cyclopentyl-1,3-dipropylxanthine (DPCPX), or their combination.

Does chronic pain alter the normal interaction between cardiovascular and pain regulatory systems? Pain modulation in the hypertensive-monoarthritic rat.

Unlabelled: Hypertension-associated hypoalgesia is widely recognized in acute pain conditions. In chronic pain states, however, the relationship between blood pressure and pain sensitivity is still ill-defined, with different authors reporting negative, positive, or even no relationship at all. This work addresses this issue, using complete Freund's adjuvant (CFA)-induced monoarthritis in different models of hypertension: Spontaneous (spontaneously hypertensive rats, SHR), induced by infusion of angiotensin II (ANG) or 1,3-dipropyl-8-sulfophenylxanthine (DPSPX, an adenosine receptors' antagonist), and renal artery ligation (RAL).

The hyperalgesic effects induced by the injection of angiotensin II into the caudal ventrolateral medulla are mediated by the pontine A5 noradrenergic cell group.

The caudal ventrolateral medulla (CVLM) is a key component of the supraspinal pain modulatory system. Pain modulation from the CVLM is partially relayed by spinally projecting noradrenergic neurons of the pontine A(5) cell group, which leave collateral fibres at the CVLM. The injection of angiotensin II (Ang II) into the CVLM was recently shown to induce hyperalgesia mediated by angiotensin type 1 (AT(1)) receptors, expressed by CVLM neurons that do not project to the spinal cord.

Role of superoxide and hydrogen peroxide in hypertension induced by an antagonist of adenosine receptors.

Treatment of Wistar rats for 7 days with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, induces long-lasting hypertension associated with marked changes in vascular structure and reactivity and renin-angiotensin system activation. This study aimed at evaluating the role of oxidative stress in the development of DPSPX-induced hypertension and also at identifying the relative contribution of superoxide radical (O2.-) vs hydrogen peroxide (H2O2).

Lesion of the caudal ventrolateral medulla prevents the induction of hypertension by adenosine receptor blockade in rats.

The continuous infusion for 7 days of the adenosine receptor antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) causes a sustained hypertension in rats, with an enhancement of sympathetic neurotransmission and activation of the renin-angiotensin system. We studied the involvement of the caudal ventrolateral medulla in the establishment of this hypertensive model by evaluating the effect of local lesioning in blood pressure (BP). Male adult Wistar rats received stereotaxic injections of 0.

Inhibition of nociceptive responses of spinal cord neurones during hypertension involves the spinal GABAergic system and a pain modulatory center located at the caudal ventrolateral medulla.

The mechanisms of hypertension-induced hypoalgesia were studied in a model of hypertension induced by adenosine receptors blockade with the non-selective antagonist 1,3-dipropyl-8-sulfophenylxanthine (DPSPX) during 7 days. Based on the positive correlation between pain thresholds and noxious-evoked expression of the c-fos protooncogene in spinal cord neurones, we used this marker of nociceptive activation of spinal neurones to evaluate the involvement of the spinal GABAergic system and the caudal ventrolateral medulla (VLM), an important inhibitory component of the supraspinal endogenous pain modulatory system. In DPSPX-treated animals, a 20% increase in blood pressure was achieved along with a decrease in Fos expression in the superficial (laminae I-II) and deep (laminae III-VII) dorsal horn.

Pre- and postjunctional effects of angiotensin II in hypertension due to adenosine receptor blockade.

Prejunctional facilitation of [3H]noradrenaline release induced by sympathetic nerve stimulation and postjunctional contractile effects of angiotensin II were studied in the mesenteric artery and vein of 1,3-dipropyl-8-sulfophenylxanthine (DPSPX)-hypertensive rats. Male Wistar rats received infusions of saline or DPSPX (90 microg/kg/h) i.p.

Scavenging of nitric oxide by an antagonist of adenosine receptors.

Chronic treatment of rats with 1,3-dipropyl-8-sulfophenylxanthine (DPSPX), an antagonist of adenosine receptors, causes hypertension, cardiovascular hypertrophy and hyperplasia and impaired endothelium-dependent vasodilatation. An accelerated degradation of nitric oxide (NO) by scavenging molecules could account for endothelial dysfunction and trophic changes in this hypertension. Our aim was to determine whether DPSPX is a scavenger of NO and if this putative effect is shared by caffeine (1,3,7-trimethylxanthine) and DPCPX (1,3-dipropyl-8-ciclopentylxanthine), which are also adenosine receptor antagonists but do not induce hypertension in rats.

Isolation and spectroscopic characterization of the membrane-bound nitrate reductase from Pseudomonas chlororaphis DSM 50135.

A nitrate reductase was solubilized with Triton X-100 from the membranes of Pseudomonas chlororaphis DSM 50135 grown microaerobically in the presence of nitrate. Like other membrane-bound nitrate reductases, it contains three subunits, of 129, 66 (64) and 24 kDa, referred to in the literature as alpha, beta and gamma, respectively. Electrocatalytic studies revealed that only the membrane-bound, not the solubilized form of the enzyme, can accept electrons from a menaquinone analog, menadione, whereas both forms can accept electrons from methylviologen.

Copper-containing nitrite reductase from Pseudomonas chlororaphis DSM 50135.

The nitrite reductase (Nir) isolated from Pseudomonas chlororaphis DSM 50135 is a blue enzyme, with type 1 and type 2 copper centers, as in all copper-containing Nirs described so far. For the first time, a direct determination of the reduction potentials of both copper centers in a Cu-Nir was performed: type 2 copper (T2Cu), 172 mV and type 1 copper (T1Cu), 298 mV at pH 7.6.

Two azurins with unusual redox and spectroscopic properties isolated from the Pseudomonas chlororaphis strains DSM 50083T and DSM 50135.

Two azurins (Az624 and Az626) were isolated from the soluble extract of two strains of Pseudomonas chlororaphis, DSM 50083(T) and DSM 50135, respectively, grown under microaerobic conditions with nitrate as final electron acceptor. The azurins, purified to electrophoretic homogeneity in three chromatographic steps, exhibit several peculiar properties. They have high reduction potentials and lower pI than most azurins described in the literature.