Studies on the Anti-Inflammatory and Anti-Nociceptive Effects of Melatonin in the Rat (original) (raw)
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Protective Effect of Melatonin in Carrageenan-Induced Acute Local Inflammation
Pharmacological Research, 2002
The aim of the present study was to investigate the protective effect of the pineal hormone melatonin in a model of acute local inflammation (carrageenan-induced paw oedema). Inflammation was assessed by measurement of nitric oxide (NO), Malondialdehyde (MDA) and glutathione levels in the paw tissue in rats. The intraplantar injection of carrageenan elicited an inflammatory response that was characterised by a time-dependent increase in paw oedema, increased level of nitrite/nitrate and MDA, a lipid peroxidation product and decreased glutathione levels in the paw tissue. The maximal increase in paw volume was observed at 4 h after administration (maximal in paw volume 160 ± 3.34 ml). In addition, NO level and MDA were markedly increased in the carrageenan-treated paw (59.96 ± 6.58 and 19.33 ± 3.35 µmol g −1 , respectively), versus in the control paw glutathione level decreased in paw tissue (3.24 ± 0.24 mol g −1). However, carrageenan-induced paw oedema was significantly reduced in a dose-dependent manner by treatment with melatonin (given at 5 and 10 mg kg −1) at 1, 2, 3, 4, 5 and 6 h after injection of carrageenan. Melatonin treatment also caused a significant reduction of the NO and MDA levels, while increasing glutathione level in the paw tissue. Our findings support the view that melatonin exerts anti-inflammatory effects. Part of these anti-inflammatory effect may be related to an inhibition of the NO and MDA production, while another part may be related to increase of the glutathione level in the paw tissue.
Melatonin administration reduces inflammatory pain in rats
Journal of Pain Research, 2012
In view of the broad range of effects attributed to melatonin, this study evaluated its analgesic effect on inflammatory pain induced by complete Freund's adjuvant (CFA) in Wistar rats. Inflammation was induced by intradermal CFA injection in the hind paw of all animals, which were then divided into two groups that received either 60 mg/kg of melatonin or vehicle (1% alcohol in saline), intraperitoneally, for three days. The analgesic effect of melatonin was assessed by the hot-plate test, immediately and thereafter at 30, 60, 90, and 120 minutes after the first administration and 24 hours after once-daily administration for 2 more days. After CFA injection, melatonin administration increased withdrawal latency at 60 minutes after the first dose. After the end of treatment, melatonin showed a significant analgesic effect on inflammatory pain. This study paves the way for exploration of how brief courses of treatment could improve this analgesic effect in the late phases of inflammatory pain.
Pain, 2015
Anti-nociceptive effects of melatonin have been documented in a wide range of experimental animal models. The aim of this study was to investigate the analgesic, anti-hyperalgesic and anti-inflammatory properties of melatonin employing a validated burn injury (BI) model in healthy male volunteers. The design was a randomized, double-blind, placebo-controlled, three-arm crossover study. Each volunteer participated in three identical study sessions with intravenous administration of either placebo, melatonin 10 mg or melatonin 100 mg. Sixty minutes after bolus injection of study medication, a BI was induced by a computerized contact thermode (47.0°C, 420 s, 5.0 x 2.5 cm). Pain ratings during the BI, and quantitative sensory testing (QST) at baseline, and, 1, 2, 4 and 6 hours after the BI, were performed. The QST included assessments of secondary hyperalgesia areas, mechanical and thermal thresholds in the BI-area, and pressure algometry. Furthermore, markers of inflammation, skin-refl...
Melatonin in Antinociception: Its Therapeutic Applications
Current Neuropharmacology, 2012
The intensity of pain sensation exhibits marked day and night variations. Since the intensity of pain perception is low during dark hours of the night when melatonin levels are high, this hormone has been implicated as one of the prime antinociceptive substances. A number of studies have examined the antinociceptive role of melatonin in acute, inflammatory and neuropathic pain animal models. It has been demonstrated that melatonin exerts antinociceptive actions by acting at both spinal cord and supraspinal levels. The mechanism of antinociceptive actions of melatonin involves opioid, benzodiazepine, α 1 -and α 2 -adrenergic, serotonergic and cholinergic receptors. Most importantly however, the involvement of MT 1 /MT 2 melatonergic receptors in the spinal cord has been well documented as an antinociceptive mechanism in a number of animal models of pain perception. Exogenous melatonin has been used effectively in the management of pain in medical conditions such as fibromyalgia, irritable bowel syndrome and migraine and cluster headache. Melatonin has been tried during surgical operating conditions and has been shown to enhance both preoperative and post-operative analgesia. The present review discusses the available evidence indicating that melatonin, acting through MT 1 /MT 2 melatonin receptors, plays an important role in the pathophysiological mechanism of pain.
Original research article, 2023
Pain is the most common reason for physician consultation. Among the currently available analgesic drugs, opioids are the most efficacious but have many unacceptable adverse effects. Melatonin has been found to have antinociceptive potential in many animal and clinical studies that need further evaluation. The study aimed to assess the antinociceptive effect of melatonin alone and in combination with pethidine. Twenty Swiss albino mice were divided into four groups, each containing five animals receiving respective drugs. Tail flick and tail clip methods were used to assess antinociceptive effect of the drug. The reaction time of each animal in each group was taken at 0 min, 30 min, 60 min, 90 min and 120 min and the experiment was conducted on day 0, day 7, day 14 and day 28. Mean reaction time averaged over day 0, day 7, day 14 and day 28 was used to make inter-group comparisons. The mean reaction time increased in all groups except group I, in both tail flick and tail clip methods suggesting an antinociceptive effect of melatonin. The mean reaction time of a combination of melatonin and pethidine was much higher than that of either pethidine alone or melatonin alone, suggesting that melatonin potentiated the effect of pethidine. The antinociceptive effect of melatonin in the dose used in the present study was comparable to that of melatonin, and melatonin potentiated antinociceptive effect of pethidine.
Effect of exogenous melatonin on acute and chronic inflammatory process in rats
Acta farmacéutica bonaerense, 2002
Melatonin influence (4 mg/kg) was investigated on acute inflammation using rat paw edema and on chronic inflammation through granuloma test and adjuvant arthritis. Melatonin inhibited the edema produced by carrageenan in acute model. However, failed to inhibit the proliferative phase in the granuloma test and the acute and chronic phase in the adjuvant arthritis. These results suggest melatonin shows different activity on the tested inflammatory models at the same doses. RESUMEN. "Efecto de melatonina exógena en procesos inflamatorios agudos y crónicos en ratas". Se investigó la influencia de melatonina (4 mg/kg) en la inflamación aguda usando el modelo de edema de pata en rata y en la inflamación crónica mediante la prueba del granuloma y artritis inducida por adyuvante. Melatonina inhibió el edema producido por carragenina en el modelo agudo, pero no presentó acción inhibitoria en la fase proliferativa de la prueba del granuloma y en la fase aguda y crónica de la artritis inducida por adyuvante. Estos resultados sugieren que melatonina, a la misma dosis, muestra diferentes comportamientos en los modelos inflamatorios ensayados.
European Journal of Medicinal Chemistry, 2007
Inflammation is characterized by vasodilatation, increase of blood flow and vascular permeability, migration of leucocytes to the inflammatory site, and production of cytokines. The aim of this study was evaluate the anti-inflammatory and antinociceptive effects of (À)-myrtenol, a plant-derived monoterpene alcohol, in mice and its possible mechanisms. Myrtenol was used in classical models of inflammation (paw oedema induced by different agents, carrageenan-induced peritonitis, myeloperoxidase levels and cytokine measurement) and nociception (acetic acid-induced writhing, hot-plate test, and paw licking induced by formalin, glutamate, and capsaicin). Pretreatment with myrtenol effectively inhibited paw oedema induced by carrageenan, compound 48/80, histamine, serotonin and prostaglandin E 2 . Myrtenol also reduced the cell counts, myeloperoxidase activity and cytokine levels (interleukin 1β, but not tumour necrosis factor-α) of the peritoneal cavity induced by carrageenan. In addition, myrtenol inhibited acetic acid-induced writhing, did not significantly prolong the latency time in the hot-plate test, decreased licking time caused by an intraplantar injection of formalin (only in the second phase), glutamate and capsaicin. Myrtenol reduces the inflammatory response and nociception in mice due to the inhibition of the release of inflammatory mediators, cell migration and also to the signalling pathway of receptors involved in the transmission of pain.
Mechanisms involved in the antinociception caused by melatonin in mice
Journal of Pineal Research, 2006
The pregnane compound MV8612 isolated from the rhizome of the plant Mandevilla velutina administered by intraperitoneal (i.p.), intrathecal (i.t.) or by intracerebroventricular (i.c.v.) routes caused graded and complete inhibition of the thermal hyperalgesia caused by i.t. injection of bradykinin (BK) in mice with mean ID values of 7.8 mmol / kg, 33.6 and 4.6 nmol / site, respectively. Compound 50 MV8612 (i.p.) also inhibited both the neurogenic and inflammatory pain responses to formalin with mean ID values of 5.6 and 10.6 50 mmol / kg, respectively. Given i.t., MV8612 produced significant inhibition of both phases of the formalin-induced licking (inhibition of 3465 and 3664%, respectively). Given by i.c.v. route MV8612 inhibited both phases of formalin-induced pain (3266 and 6365%) with mean ID of 8.4 nmol / site against the late phase. MV8612, given by i.p., i.c.v. or i.t. routes, also inhibited capsaicin-induced pain 50 1 (5164, 2568 and 3966%, respectively). The i.t. injection of potassium (K ) channel blockers, apamin and charybdotoxin given 15 min before, markedly prevented the antinociception of MV8612 against both phases of formalin-induced nociception. In contrast, tetraethylammonium (TEA) or glibenclamide had no effect. The i.c.v. treatment with pertussis toxin resulted in a significant inhibition of both MV8612-and morphine-induced antinociception against both phases of formalin-induced pain. Taken together these results confirm and also extend our previous data by demonstrating that the greater part of the antinociception caused by MV8612 seems to be associated 21 1
2010
Melatonin is a natural hormone-like compound mainly produced by the pineal gland. It possesses a number of important biologic activities including oncostatic, anti-oxidant and immunostimulatory actions; however, the dose-response relationship was not well characterized. The present study was designed to evaluate the dose-response relationship for the anti-inflammatory activity of melatonin in the experimental animal model of formalin-induced chronic inflammation in rats. Fifty-four Sprague-Dawley rats were allocated into 9 subgroups, 6 rats in each one. These subgroups represent saline-treated, piroxicam (5mg/kg), dexamethasone (1mg/kg) and melatonin (0.25, 0.5, 1.0, 2.0, 5 and 10mg/kg) treated subgroups. All drugs were administered intraperitonealy (IP) 30 min before inducing inflammation by injecting 0.1 ml of 2% formalin into the subplanter surface of the right hind paw of ether-anesthetized rats and continued for 7 consecutive days. The results of the study showed that all treatment groups (except melatonin 0.25 mg/kg) significantly reduced paw thickness (P<0.05) compared to saline treated group after 7 days of treatment. Melatonin 5 mg/kg group produced a highest level of anti-inflammatory activity, which is comparable to that of piroxicam 5mg/kg group. In conclusion, melatonin exerts a well defined anti-inflammatory activity in animal model of chronic inflammation that is comparable in certain circumstances to that produced by standard drugs in this respect.
Efecto de melatonina exógena en procesos inflamatorios agudos y crónicos en ratas
Acta Farmacéutica Bonaerense, 2002
Melatonin influence (4 mg/kg) was investigated on acute inflammation using rat paw edema and on chronic inflammation through granuloma test and adjuvant arthritis. Melatonin inhibited the edema produced by carrageenan in acute model. However, failed to inhibit the proliferative phase in the granuloma test and the acute and chronic phase in the adjuvant arthritis. These results suggest melatonin shows different activity on the tested inflammatory models at the same doses. RESUMEN. "Efecto de melatonina exógena en procesos inflamatorios agudos y crónicos en ratas". Se investigó la influencia de melatonina (4 mg/kg) en la inflamación aguda usando el modelo de edema de pata en rata y en la inflamación crónica mediante la prueba del granuloma y artritis inducida por adyuvante. Melatonina inhibió el edema producido por carragenina en el modelo agudo, pero no presentó acción inhibitoria en la fase proliferativa de la prueba del granuloma y en la fase aguda y crónica de la artritis inducida por adyuvante. Estos resultados sugieren que melatonina, a la misma dosis, muestra diferentes comportamientos en los modelos inflamatorios ensayados.