crocin and Pain

Crocin, a water-soluble carotenoid, is known as a pharmacologically active compound, particularly for its potent anti-oxidant activity. The present work provides a comprehensive review of the available literature concerning the anti-inflammatory properties of crocin in various organs/systems as well as its anti-nociceptive effects. PubMed, Scopus, and Web of Science electronic databases were systematically searched up to 28 March 2020 to detect all relevant preclinical and human studies in accordance with the Preferred Reporting Items for Systematic Reviews and Meta-analyses (PRISMA) statement. In total, 104 studies were included for qualitative synthesis. This systematic search and review indicated that crocin not only combats reactive oxygen species production and suppresses pro-inflammatory cytokines secretion but also alleviates inflammation in various organs (e.g. the lung, heart, brain, and kidney), in a series of animal models and in vitro experiments, via regulating mainly NF-κB pathway and NF-κBp65 translocation to the cell nucleus. In this context, modulation of PI3K/Akt appears to be a favorable crocin target contributing to NF-κB pathway inhibition. Even though data is limited in humans with only one clinically relevant study retrieved, the results of preclinical studies regarding anti-inflammatory/anti-nociceptive effects of crocin are promising and warrant further testing in clinical settings.

Topics: Animals; Anti-Inflammatory Agents; Carotenoids; Cytokines; Gene Expression Regulation; Humans; Inflammation; Pain

The purpose of this study was to investigate the effects of Crocin on brain neuroterophins, cognition, sensory and motor dysfunction and compare to fingolimod effects in toxic-induced demyelination with Ethidium Bromide EB in female Wistar rats.. Animals were assigned in to 8 groups; Sham, Sham operated (ShOp), EAE, crocin treated, Vehicle, Fingolompd (Fing) and fingolimod + crocin (Cr+Fing). Demyelination was induced by single dose injection of 10 μl of EB 0.1 percent into the fourth ventricle of the brain. Crocin and fingolimod were administered for 21 days, daily, oral gavage. BDNF, NGF1, tail flake latency, balance and behavioral variables were sampled and analyzed by paired t-test and ANOVA test with repeated post hoc measurements.. The results showed that crocin improves all studied factors, but remarkable improvements were observed in dosage of 10 mg/kg. Crocin (10mg/kg) and fingolimod (1mg/kg) significantly improved cognition variables in open field test, sensory and motor nerve conduction velocity, tail flick latency and clinical scores (p less than 005). In addition, applying of crocin co-administered with fingolimod led to significant increases in all assessed factors, greater than crocin or fingolimod intervention alone.. Based on the current findings, crocin can improve the level of brain neurotrophins, exploratory behavior, balance and pain after toxin-demyelination as close as fingolimod results.

Topics: Animals; Brain; Cognition; Demyelinating Diseases; Female; Fingolimod Hydrochloride; Nerve Growth Factors; Pain; Rats; Rats, Wistar

Crocin and safranal are the active substances of saffron and have many biological properties. In the present study, we compared the effects of crocin, safranal and diclofenac on local inflammation and its induced pain in rats.. Local inflammation was induced by intraplantar (ipl) injection of carrageenan (100 μl, 2%). Paw thickness was measured before and after carrageenan injection. Inflammatory pain responses including cold allodynia, mechanical allodynia and hyperalgesia were assessed using acetone spray and von Frey filament tests, respectively. The number of neutrophils in inflammatory zone was counted 6.5 h after injection of carrageenan.. Carrageenan produced edema, cold allodynia, mechanical allodynia and hyperalgesia and caused neutrophil infiltration in paw tissues. Crocin at doses of 25, 50 and 100 mg/kg, safranal at doses of 0.5, 1 and 2 mg/kg and diclofenac (as a reference drug) at a dose of 10 mg/kg attenuated edema, suppressed inflammatory pain responses and decreased the number of neutrophils.. The present study showed anti-inflammatory and antinociceptive activities for crocin, safranal and diclofenac in carrageenan model of local inflammation and inflammatory pain.

Topics: Analgesics; Animals; Anti-Inflammatory Agents; Carotenoids; Carrageenan; Cyclohexenes; Diclofenac; Disease Models, Animal; Dose-Response Relationship, Drug; Edema; Hyperalgesia; Inflammation; Male; Neutrophil Infiltration; Pain; Pain Threshold; Rats; Rats, Wistar; Terpenes; Time Factors

In this study, the effects of intraperitoneal (i.p.) injection of crocin in the absence and presence of subcutaneous (s.c.) injections of morphine and naloxone were investigated on the formalin test in rats. The formalin test was induced by intra-plantar (i.pl.) injection of formalin (50 microL, 1%), and the time spent licking and biting of the injected paw was measured for 1 h. Formalin induced a marked biphasic (first phase: 0-5 min and second phase: 15-45 min) pain response. Morphine (1 mg/kg, s.c.) significantly (p < 0.05) suppressed both phases of pain. Naloxone (2 mg/kg, s.c.) alone did not change the intensity of pain, but pretreatment with naloxone (2 mg/kg) significantly (p < 0.05) prevented morphine (1 mg/kg)-induced antinociception. Crocin at doses of 50, 100 and 200 mg/kg significantly (p < 0.05) attenuated pain. Crocin (100 mg/kg, i.p.) significantly (p < 0.05) increased the morphine (1 mg/kg, s.c.)-induced antinociception. Naloxone (2 mg/kg) did not reverse the suppressive effect of crocin (100 mg/kg) on pain. Crocin at a dose of 400 mg/kg significantly (p < 0.05) suppressed locomotor activities. These findings indicate that morphine through a naloxone-sensitive mechanism produced analgesia. Crocin produced a dose-dependent antinociceptive effect. In addition, crocin increased morphine-induced antinociception, but naloxone did not change the antinociceptive effect of crocin.

Topics: Analgesia; Analgesics, Opioid; Animals; Carotenoids; Male; Morphine; Motor Activity; Naloxone; Pain; Pain Measurement; Rats; Rats, Wistar

In this study, the effects of intraperitoneal (i.p.) and intracerebroventricular (i.c.v.) injection of crocin in separate and combined treatments with i.p. injections of morphine (an opioid receptor agonist) and naloxone (an opioid receptor antagonist) were investigated on acute corneal pain in rats. Acute corneal pain was induced by local application of a drop of 5 M NaCl solution on the corneal surface. The number of eye wipes was taken as a pain response, and counted during the first 30 s. Crocin injected i.p. and i.c.v. and morphine injected i.p. significantly (p < 0.05) decreased the number of eye wipes. Morphine (i.p.)-induced antinociception was significantly (p < 0.05) increased by the systemically and centrally injected crocin. The antinociceptive effects induced by i.p. and i.c.v. injections of crocin were not reversed by i.p. injection of naloxone. These findings indicated that both crocin and morphine attenuated hypertonic saline-induced corneal pain. The opioid receptors may not be involved in the analgesic mechanism of crocin.

Topics: Analgesics, Opioid; Animals; Carotenoids; Cornea; Drug Combinations; Injections, Intraperitoneal; Injections, Intraventricular; Male; Morphine; Naloxone; Pain; Pain Measurement; Rats; Rats, Wistar