fumarates and Pain

Psoriasis vulgaris may benefit from treatment with fumaric acid and/or its derivatives; however, because different preparations have been used, results have been contradictory and difficult to interpret.. The purpose of this clinical trial was to evaluate the therapeutic value of fumaric acid derivatives.. A randomized double-blind study was carried out in patients with psoriasis, comparing a well-characterized formulation of fumaric acid derivatives with placebo.. The results indicated statistically significant superiority of the fumaric acid derivatives over placebo. Adverse events (flush, gastrointestinal disturbances) were initially relatively frequent, but decreased thereafter.. Fumaric acid derivatives were found to be effective and safe in the treatment of psoriasis.

Topics: Abdominal Pain; Adult; Aged; Diarrhea; Dimethyl Fumarate; Double-Blind Method; Drug Combinations; Female; Flushing; Fumarates; Humans; Joints; Male; Middle Aged; Pain; Placebos; Psoriasis; Remission Induction

Topics: Administration, Oral; Amides; Analgesics; Analysis of Variance; Aspirin; Caffeine; Clinical Trials as Topic; Codeine; Differential Threshold; Drug Evaluation; Electric Stimulation; Fumarates; Humans; Pain; Phenacetin; Phenobarbital; Piperidines; Placebos; Propionates; Pyridines; Toothache

Neuroplasticity in the amygdala, a brain center for emotions, leads to increased neuronal activity and output that can generate emotional-affective behaviors and modulate nocifensive responses. Mechanisms of increased activity in the amygdala output region (central nucleus, CeA) include increased reactive oxygen species, and so we explored beneficial effects of monomethyl fumarate (MMF), which can have neuroprotective effects through the nuclear factor (erythroid-derived 2)-like 2 (Nrf2) antioxidant response pathway. Systemic (intraperitoneal) MMF dose-dependently inhibited vocalizations and mechanosensitivity (hindlimb withdrawal reflexes) of rats in an arthritis pain model (kaolin-carrageenan-induced monoarthritis in the knee). Stereotaxic administration of MMF into the CeA by microdialysis also inhibited vocalizations but had a limited effect on mechanosensitivity, suggesting a differential contribution to emotional-affective vs sensory pain aspects. Extracellular single-unit recordings of CeA neurons in anesthetized rats showed that stereotaxic administration of MMF into the CeA by microdialysis inhibited background activity and responses of CeA neurons to knee joint stimulation in the arthritis pain model. Monomethyl fumarate had no effect on behaviors and neuronal activity under normal conditions. The results suggest that MMF can inhibit emotional-affective responses in an arthritis pain model through an action that involves the amygdala (CeA).

Topics: Amygdala; Animals; Arthritis; Disease Models, Animal; Fumarates; Male; Maze Learning; Neuronal Plasticity; Neurons; Pain; Rats, Sprague-Dawley; Vocalization, Animal

In the present study, we have investigated the anti-nociceptive and anti-allodynic activity of the renin inhibitor, aliskiren, in various pain models. The anti-nociceptive activity of aliskiren was investigated in chemically-induced pain, orofacial pain and centrally mediated pain models. Anti-allodynic activity was evaluated in post-operative and neuropathic pain models. The levels of TNF-α and IL-6 were measured in homogenates of hind paw as markers of inflammation in formalin injected mice. Intraperitoneal administration of aliskiren (1-50mg/kg) showed anti-nociceptive activity in the writhing test, formalin hind paw test, capsaicin induced pain, and orofacial pain tests in ICR mice in a dose dependent manner. Aliskiren (50mg/kg, i.p.) reduced levels of TNF-α and IL-6 in hind paw homogenates of formalin-injected mice. Aliskiren (50mg/kg, i.p.) did not show any analgesic activity in hot-plate and tail-flick tests, indicating the absence of centrally mediated anti-nociceptive effects. On the other hand, intra-plantar administration of aliskiren (0.1, 0.5 and 1mg) showed analgesic activity in rat formalin tests, indicating a locally mediated effect. Aliskiren (30-100mg/kg, i.p.) showed anti-allodynic activity in post-operative pain and chronic constriction injury-induced neuropathic pain in Sprague Dawley rats. This data suggests that aliskiren may have the potential to be used as an anti-nociceptive and anti-allodynic agent.

Topics: Acetic Acid; Amides; Analgesics; Animals; Behavior, Animal; Capsaicin; Female; Formaldehyde; Fumarates; Hot Temperature; Hyperalgesia; Male; Mice; Mice, Inbred ICR; Motor Activity; Pain; Rats; Rats, Sprague-Dawley

Topics: Amides; Analgesics; Animals; Cough; Dose-Response Relationship, Drug; Drug Antagonism; Drug Evaluation, Preclinical; Drug Synergism; Edema; Female; Fumarates; Hindlimb; Humans; Male; Motor Activity; Pain; Piperidines; Propionates; Pyridines; Respiration; Self Medication; Spasm; Substance Withdrawal Syndrome; Tail

Topics: Administration, Oral; Amides; Analgesics; Differential Threshold; Electric Stimulation; Female; Fumarates; Humans; Male; Motor Activity; Pain; Piperidines; Propionates; Pyridines; Reflex, Pupillary; Stereoisomerism

Topics: Acute Disease; Amides; Analgesics; Chronic Disease; Drug Combinations; Drug Evaluation; Female; Fumarates; Humans; Male; Nerve Compression Syndromes; Neuralgia; Pain; Piperidines; Propionates; Pyridines

Topics: Amides; Analgesics; Colic; Drug Evaluation; Female; Fumarates; Headache; Humans; Male; Neuralgia; Pain; Pain, Postoperative; Piperidines; Propionates; Pyridines; Sampling Studies; Suppositories

Topics: Analgesia; Animals; Brain; Brain Chemistry; Chickens; Chromatography, Gas; Citrates; Citric Acid Cycle; Foot; Fumarates; Ketoglutaric Acids; Lactates; Malates; Malonates; Morphine; Pain; Pyruvates; Succinates

Topics: Autonomic Nervous System; Cycloheptanes; Fumarates; Humans; Locomotion; Motor Activity; Muscle Proteins; Muscles; Muscular Diseases; Pain; Parasympatholytics; Propylamines; Rheumatic Diseases; Vasodilator Agents; Vasomotor System

Topics: Blood Coagulation; Cycloheptanes; Fumarates; Humans; Pain; Parasympatholytics; Propylamines; Skin Temperature; Tranquilizing Agents; Vascular Diseases; Vasodilator Agents

Topics: Adult; Aged; Arteries; Cerebrovascular Circulation; Cycloheptanes; Female; Fumarates; Humans; Leg; Male; Middle Aged; Pain; Parasympatholytics; Paresthesia; Propylamines; Vascular Diseases

Topics: Analgesics; Animals; Aspirin; Codeine; Dextropropoxyphene; Dogs; Female; Fumarates; Inflammation; Male; Mice; Nalorphine; Pain; Propionates; Pyrrolidines; Rats