Treatment with 5-fluoro-2-oxindole Increases the Antinociceptive Effects of Morphine and Inhibits Neuropathic Pain.

This study investigates whether the administration of an oxindole, 5-fluoro-2-oxindole, could inhibit the nociceptive and emotional behaviors and increase the effectiveness of morphine via modulating the microglia and activating the nuclear factor erythroid-2 related factor 2 (Nrf2) signaling pathway and MOR expression. In C57BL/6 mice with neuropathic pain provoked by the total constriction of sciatic nerve we studied the effects of 10 mg/kg 5-fluoro-2-oxindole in: (i) the allodynia and hyperalgesia caused by the injury; (ii) the anxiety- and depressive-like behaviors; (iii) the local antinociceptive actions of morphine; (iv) the expression of CD11b/c (a microglial marker), the antioxidant and detoxificant enzymes Nrf2, heme oxygenase 1 (HO-1) and NAD(P)H:quinone oxidoreductase-1 (NQO1), and of MOR in the spinal cord and hippocampus. Results showed that the inhibition of the main nociceptive symptoms and the anxiety- and depressive-like behaviors induced by 5-fluoro-2-oxindole were accompanied with the suppression of microglial activation and the activation of Nrf2/HO-1/NQO1 signaling pathway in the spinal cord and/or hippocampus. This treatment also potentiated the pain-relieving activities of morphine by normalizing the reduced MOR expression. This work demonstrates the antinociceptive, anxiolytic and antidepressant effects of 5-fluoro-2-oxindole, suggests a new strategy to enhance the antinociceptive actions of morphine and proposes a new mechanism of action of ...
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research

Related Links:

Abstract Gut inflammation or injury causes intestinal hypersensitivity (IHS) and hyperalgesia, which can persist after the initiating pathology resolves, are often referred to somatic regions and exacerbated by psychological stress, anxiety or depression, suggesting the involvement of both the spinal cord and the brain. The supraspinal mechanisms of IHS remain to be fully elucidated, however, over the last decades the series of intestinal pathology-associated neuroplastic changes in the brain has been revealed, being potentially responsible for the phenomenon. This paper reviews current clinical and experimental d...
Source: Cellular and Molecular Neurobiology - Category: Cytology Authors: Tags: Cell Mol Neurobiol Source Type: research
Phantom limb pain (PLP) is a type of chronic pain that follows limb amputation, brachial plexus avulsion injury, or spinal cord injury. Treating PLP is a well-known challenge. Currently, virtual reality (VR) interventions are attracting increasing attention because they show promising analgesic effects. However, most previous studies of VR interventions were conducted with a limited number of patients in a single trial. Few studies explored questions such as how multiple VR sessions might affect pain over time, or if a patient's ability to move their phantom limb may affect their PLP. Here we recruited five PLP patients to...
Source: Frontiers in Neurology - Category: Neurology Source Type: research
One of my most popular posts ever is one I wrote many years ago on malingering. Secondary gain, like malingering or symptom magnification is one of those terms used by people who don’t live with persistent pain, and commonly used when a person with pain doesn’t seem to be progressing “as expected”. The term is an old one, originating in the psychoanalytic literature, brought into compensation and insurance environments but never really examined (Fishbain, Rosomoff, Cutler &Rosomoff, 1995) until well after it had become a popular label. Freud first identified the potential for gains from bein...
Source: HealthSkills Weblog - Category: Anesthesiology Authors: Tags: Assessment Chronic pain Professional topics Research malingering secondary gain stigma Source Type: blogs
AbstractObjectivesTraumatic peripheral nerve injuries (PNI) often result in severe neuropathic pain which typically becomes chronic, is recalcitrant to common analgesics, and is associated with sleep disturbances, anxiety, and depression. Pharmacological treatments proven to be effective against neuropathic pain are not well tolerated due to side effects. Neuromodulative interventions such as peripheral nerve or spinal cord stimulation have generated mixed results and may be limited by reduced somatotopic specificity. Dorsal root ganglion (DRG) stimulation may be more effective in this etiology.Materials and MethodsTwenty ...
Source: Neuromodulation: Technology at the Neural Interface - Category: Biotechnology Authors: Tags: Clinical Research Source Type: research
What does physical pain have to do with depression, and vice versa? On today’s Psych Central Podcast, our guest, Dr. Jack Stern, a board-certified neurosurgeon specializing in spinal surgery, explains the psychology of pain and how the two are inextricably linked. Dr. Stern describes how pain can lead to depression and how depression can intensify physical pain. We also find out why opioids don’t work for chronic pain, and how past pain affects current pain. Join us for an in-depth discussion on physical pain and mental health. SUBSCRIBE &REVIEW Guest information for ‘Dr. Jack Stern- Chronic Pain&r...
Source: World of Psychology - Category: Psychiatry & Psychology Authors: Tags: Chronic Pain Depression Disorders General Interview Mental Health and Wellness Podcast Psychology The Psych Central Show Source Type: blogs
This study aims to evaluate the alleviative effect of intra-amygdala microinfusion of a pharmacological antagonist of P2X7R (A-438079) on NP and explore its possible mechanism of action. Male Sprague-Dawley rats were used to construct the animal model of NP through spared nerve injury (SNI). The SNI rats randomly received chronic bilateral microinjection of A-438079 (100 pmol/side) or saline into the amygdalae via cannulas. Mechanical paw withdrawal threshold (MWT) and thermal withdrawal duration (TWD) were measured by von Frey monofilaments. Besides, tail suspension test (TST), forced swimming test (FST), open field test ...
Source: Brain, Behavior, and Immunity - Category: Neurology Authors: Tags: Brain Behav Immun Source Type: research
Molecules, Vol. 25, Pages 1120: Building and Testing PPARγ Therapeutic ELB00824 with an Improved Therapeutic Window for Neuropathic Pain Molecules doi: 10.3390/molecules25051120 Authors: Westlund Zhang Effective, non-addictive therapeutics for chronic pain remain a critical need. While there are several potential therapeutics that stimulate anti-inflammatory mechanisms to restore homeostasis in the spinal dorsal horn microenvironment, the effectiveness of drugs for neuropathic pain are still inadequate. The convergence of increasing knowledge about the multi-factorial mechanisms underlying neuropathic pai...
Source: Molecules - Category: Chemistry Authors: Tags: Review Source Type: research
Conclusion: These findings support the hypothesis that in FM a deteriorated function of cortical inhibition, indexed by a higher SICI parameter, a lower function of the DPMS, together with a higher level of BDNF indicate that FM has different pathological substrates from depression. They suggest that an up-regulation phenomenon of intracortical inhibitory networks associated with a disruption of the DPMS function occurs in FM. Introduction Major depressive disorder (MDD) and fibromyalgia (FM) present overlapped symptoms. Although the connection between these two disorders has not been elucidated yet, the disruption...
Source: Frontiers in Human Neuroscience - Category: Neuroscience Source Type: research
AbstractThis systematic review and meta-analysis aims to evaluate the effectiveness of internet-delivered cognitive behavioural therapy (ICBT) on anxiety and depression among persons with chronic health conditions. A systematic database search was conducted of MEDLINE, CINAHL, PsycInfo, EMBASE, and Cochrane for relevant studies published from 1990 to September 2018. A study was included if the following criteria were met: (1) randomized controlled trial involving an ICBT intervention; (2) participants experienced a chronic health condition; (3) participants ≥ 18 years of age; and (4) effects of ICBT on anxie...
Source: Journal of Behavioral Medicine - Category: Psychiatry Source Type: research
Objective: This longitudinal study examined the unique relationship between anxiety, symptoms (pain intensity, sleep disturbance, fatigue severity), and function domains (self-reported cognitive function, physical function, satisfaction with social roles) in individuals with chronic physical conditions, independent of depressive symptoms. Method: Three surveys were mailed on an approximately yearly basis to community-dwelling adults with one of four chronic physical conditions (spinal cord injury, multiple sclerosis, muscular dystrophy, postpoliomyelitis syndrome). The first survey was completed by 1594 individuals (T1). O...
Source: Rehabilitation Psychology - Category: Rehabilitation Source Type: research
More News: Antidoxidants | Anxiety | Back Pain | Brain | Chronic Pain | Cytology | Depression | Morphine | Neurology | Pain | Spinal Cord Injury | Study