Intravenous neural stem cells abolish nociceptive hypersensitivity and trigger nerve regeneration in experimental neuropathy.

A nonphysiological repair of the lesioned nerve leading to the formation of neurinomas, altered nerve conduction, and spontaneous firing is considered the main cause of the events underlying neuropathic pain. It was investigated whether neural stem cell (NSCs) administration could lead to a physiological nerve repair, thus to a reduction of neuropathic pain symptoms such as hyperalgesia and allodynia in a well-established model of this pain (sciatic nerve chronic constriction injury [CCI]). Moreover, since we and others showed that the peripheral nerve lesion starts a cascade of neuroinflammation-related events that may maintain and worsen the original lesion, the effect of NSCs on sciatic nerve pro- and antiinflammatory cytokines in CCI mice was investigated.

The soy isoflavone genistein reverses oxidative and inflammatory state, neuropathic pain, neurotrophic and vasculature deficits in diabetes mouse model.

Treatment of diabetes complications remains a substantial challenge. The aim of this study was to explore the ability of the soy isoflavone genistein in attenuating the signs that follow diabetes onset: nociceptive hypersensitivity, oxidative and inflammatory state, nerve growth factor (NGF) decrease and vascular dysfunctions. Genistein (3 and 6 mg/kg) was administered to C57BL/6J streptozotocin diabetic mice from the 2nd till the 5th week after disease induction.

Neuroprotective effects of genistein in Mongolian gerbils: estrogen receptor-β involvement.

Genistein is a naturally occurring plant-derived phytoestrogen, present in the human diet, known to possess some beneficial effects. The present study investigated the effect of genistein on neuroprotection evaluated through electroencephalographic and behavioural correlates in a model of global cerebral ischemia in gerbils. Over the dose range tested, genistein (3 and 10 mg/kg), given 5 min after recirculation antagonized the ischemia-induced electroencephalographic total spectral power decrease 7 days after ischemia; fully prevented ischemia-induced hyperlocomotion evaluated 1 day after ischemia; reversed ischemia-induced memory impairment evaluated through both nest building behaviour and object recognition test; decreased malondialdehyde overproduction in the brain, evaluated 7 days after reperfusion; and fully promoted the survival of pyramidal cells in the CA(1) hippocampal subfield.

Murine models of human neuropathic pain.

Neuropathic pain refers to pain that originates from pathology of the nervous system. Diabetes, infection (herpes zoster), nerve compression, nerve trauma, and autoimmune diseases are examples of diseases that may cause neuropathic pain. Unfortunately no satisfactory treatment is yet available for this type of pain.

Beneficial effects of a Cannabis sativa extract treatment on diabetes-induced neuropathy and oxidative stress.

Neuropathy is the most common complication of diabetes and it is still considered to be relatively refractory to most of the analgesics. The aim of the present study was to explore the antinociceptive effect of a controlled cannabis extract (eCBD) in attenuating diabetic neuropathic pain. Repeated treatment with cannabis extract significantly relieved mechanical allodynia and restored the physiological thermal pain perception in streptozotocin (STZ)-induced diabetic rats without affecting hyperglycemia.

Genistein, a natural phytoestrogen from soy, relieves neuropathic pain following chronic constriction sciatic nerve injury in mice: anti-inflammatory and antioxidant activity.

There is great interest in soy isoflavones as alternatives to endogenous estrogens not only in hormonal pathologies, but also in inflammatory, neurodegenerative diseases, and pain. We investigated the effect of the isoflavone genistein on neuropathic pain. Genistein binds estrogen receptors (ER) with higher affinity for the ERbeta particularly expressed in neuronal and immune cells.

Antihyperalgesic effect of a Cannabis sativa extract in a rat model of neuropathic pain: mechanisms involved.

This study aimed to give a rationale for the employment of phytocannabinoid formulations to treat neuropathic pain. It was found that a controlled cannabis extract, containing multiple cannabinoids, in a defined ratio, and other non-cannabinoid fractions (terpenes and flavonoids) provided better antinociceptive efficacy than the single cannabinoid given alone, when tested in a rat model of neuropathic pain. The results also demonstrated that such an antihyperalgesic effect did not involve the cannabinoid CB1 and CB2 receptors, whereas it was mediated by vanilloid receptors TRPV1.

The endogenous fatty acid amide, palmitoylethanolamide, has anti-allodynic and anti-hyperalgesic effects in a murine model of neuropathic pain: involvement of CB(1), TRPV1 and PPARgamma receptors and neurotrophic factors.

Palmitoylethanolamide (PEA) is an endogenous lipid that is thought to be involved in endogenous protective mechanisms activated as a result of stimulation of inflammatory response. In spite of the well demonstrated anti-inflammatory properties of PEA, its involvement in controlling pain pathways still remains poorly characterized. On this basis, we tested the efficacy of PEA in vivo against a peculiar persistent pain, such as neuropathic one.

Transient early expression of TNF-alpha in sciatic nerve and dorsal root ganglia in a mouse model of painful peripheral neuropathy.

The proinflammatory cytokine tumor necrosis factor-alpha (TNF) is an important mediator in neuropathic pain. We investigated the temporal pattern of TNF mRNA expression in the sciatic nerve, in dorsal root ganglia (DRG) and spinal cord in the mouse chronic constriction injury model of neuropathy with quantitative real-time polymerase chain reaction. Neuropathic pain-like behaviour was monitored by evaluating thermal hyperalgesia and mechanical allodynia.

Altered peripheral myelination in mice lacking GABAB receptors.

Emerging evidence implicates gamma-aminobutyric acid type B (GABA(B)) receptors in peripheral nervous system (PNS) functions. In order to elucidate which biochemical, morphological and functional parameters of peripheral nerve fibers depend on GABA(B) receptors we studied GABA(B1)-deficient mice, which are devoid of functional GABA(B) receptors. Here, we show that GABA(B1)-deficient mice exhibit morphological and molecular changes in peripheral myelin, including an increase in the number of irregular fibers and increases in the expression levels of the myelin proteins PMP22 and P0.

The purinergic antagonist PPADS reduces pain related behaviours and interleukin-1 beta, interleukin-6, iNOS and nNOS overproduction in central and peripheral nervous system after peripheral neuropathy in mice.

Neuropathic pain consequent to peripheral injury is associated with local inflammation and overexpression of nitric oxide synthases (NOS) and inflammatory cytokines in locally recruited macrophages, Schwann and glial cells. We investigated the time course and localization of nitric oxide synthases (NOS) and cytokines in the central (spinal cord and thalamus) and peripheral nervous system (nerve and dorsal root ganglia), in a mouse model of mononeuropathy induced by sciatic nerve chronic constriction injury. ATP is recognized as an endogenous pain mediator.

The non-psychoactive cannabis constituent cannabidiol is an orally effective therapeutic agent in rat chronic inflammatory and neuropathic pain.

Cannabidiol, the major psycho-inactive component of cannabis, has substantial anti-inflammatory and immunomodulatory effects. This study investigated its therapeutic potential on neuropathic (sciatic nerve chronic constriction) and inflammatory pain (complete Freund's adjuvant intraplantar injection) in rats. In both models, daily oral treatment with cannabidiol (2.

AM404, an inhibitor of anandamide uptake, prevents pain behaviour and modulates cytokine and apoptotic pathways in a rat model of neuropathic pain.

An attractive alternative to the use of direct agonists at the cannabinoid receptor type 1 (CB1) in the control of neuropathic pain may be to potentiate the actions of endogenous cannabinoids. Thus, the effects of AM404, an inhibitor of anandamide uptake, were assessed in an experimental model of neuropathic pain in rats. Daily treatment with AM404 prevented, time- and dose-dependently, the development of thermal hyperalgesia and mechanical allodynia in neuropathic rats.

Damaging effects of gliadin on three-dimensional cell culture model.

Aim: To evaluate the effects of gliadin on the oxidative environment in the "in vivo-like" model of a three-dimensional cell culture system.

Methods: LoVo cell line (intestinal adenocarcinoma) multicellular spheroids were treated with digested gliadin (with albumin used as a control). Spheroid volumes, cell viability and morphology, lactate dehydrogenase (LDH) release, content of reduced glutathione (GSH) and activity of GSH-related enzymes were examined.

Effect of the cannabinoid CB1 receptor antagonist, SR141716, on nociceptive response and nerve demyelination in rodents with chronic constriction injury of the sciatic nerve.

Many reports have shown the efficacy of cannabinoid agonists in chronic pain, whereas no report exists concerning the potential effect of cannabinoid antagonists following prolonged treatment. We tested the effects of repeated administration of the selective cannabinoid receptor type 1 (CB1) antagonist, SR141716 (rimonabant), in rats with chronic constriction injury of the sciatic nerve (CCI), an animal model of neuropathic pain. The repeated oral administration of SR141716 (1, 3 and 10 mg/kg, once a day for 1 week, from day 7 after the injury) dose dependently attenuated both thermal and mechanical hyperalgesia.

Vanilloid TRPV1 receptor mediates the antihyperalgesic effect of the nonpsychoactive cannabinoid, cannabidiol, in a rat model of acute inflammation.

Cannabidiol (CBD), a nonpsychoactive marijuana constituent, was recently shown as an oral antihyperalgesic compound in a rat model of acute inflammation. We examined whether the CBD antihyperalgesic effect could be mediated by cannabinoid receptor type 1 (CB1) or cannabinoid receptor type 2 (CB2) and/or by transient receptor potential vanilloid type 1 (TRPV1). Rats received CBD (10 mg kg(-1)) and the selective antagonists: SR141716 (N-(piperidin-1-yl)-5-(4-chlorophenyl)-1-(2,4-dichlorophenyl)-4-methyl-1H-pyrazole-3-carboxamide) for CB1, SR144528 (N-[(1S)-endo-1,3,3-trimethylbicyclo[2.

Oral anti-inflammatory activity of cannabidiol, a non-psychoactive constituent of cannabis, in acute carrageenan-induced inflammation in the rat paw.

Cannabidiol, the major non-psychoactive component of marijuana, has various pharmacological actions of clinical interest. It is reportedly effective as an anti-inflammatory and anti-arthritic in murine collagen-induced arthritis. The present study examined the anti-inflammatory and anti-hyperalgesic effects of cannabidiol, administered orally (5-40 mg/kg) once a day for 3 days after the onset of acute inflammation induced by intraplantar injection of 0.

Therapeutic effect of the endogenous fatty acid amide, palmitoylethanolamide, in rat acute inflammation: inhibition of nitric oxide and cyclo-oxygenase systems.

1. The anti-inflammatory activity of the endogenous fatty acid amide palmitoylethanolamide and its relationship to cyclo-oxygenase (COX) activity, nitric oxide (NO) and oxygen free radical production were investigated in the rat model of carrageenan-induced acute paw inflammation and compared with the nonsteroidal anti-inflammatory drug (NSAID) indomethacin. 2.

Chronic treatment with the endocannabinoid anandamide increases cytochrome P450 metabolizing system in the rat.

The aim of this work was to investigate the effects of single and repeated administration of the endogenous cannabinoid anandamide (20 mg/kg i.p.) on cytochrome P450-mediated biotransformation in the rat.

Antiinflammatory action of endocannabinoid palmitoylethanolamide and the synthetic cannabinoid nabilone in a model of acute inflammation in the rat.

1. The antiinflammatory activity of synthetic cannabinoid nabilone in the rat model of carrageenan-induced acute hindpaw inflammation was compared with that of the endocannabinoid palmitoylethanolamide and the nonsteroidal antiinflammatory drug indomethacin. 2.