Melatonin administration reduces inflammatory pain in rats

Laste, Gabriela; Macedo, Isabel Cristina de; Rozisky, Joanna Ripoll; Silva, Fernanda Ribeiro da; Caumo, Wolnei; Torres, Iraci Lucena da Silva

doi:10.2147/jpr.s34019

Cited by 17 publications

(14 citation statements)

References 22 publications

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“…In addition, melatonin improves wound healing in pinealectomized animals [38]. Melatonin also reduces pain in rodents [39,40,41,42] due to a direct action on the opiatergic centers in the central nervous system [20,40]. In the present study, the normal daily variation in melatonin was restored 1 day after the surgery, suggesting that this is the time required to initiate the healing processes that follows the surgery.…”

Section: Discussionsupporting

confidence: 55%

“…Melatonin was shown to inhibit inflammatory and neurogenic pain by impairing the local production of pain mediators or by inducing the release of endogenous endorphins [18,19,20]. Some clinical studies designed to test melatonin as an analgesic confirmed its effect in reducing pain and morphine consumption [20,21,22,23], while others concluded that melatonin ameliorates anxiety; however, the analgesic effect requires further investigation [24]. Theoretically, if the reduction in nocturnal melatonin is relevant to mounting an innate immune response, the administration of melatonin as a premedication could interfere with the healing process.…”

Section: Introductionmentioning

confidence: 99%

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The Concept of the Immune-Pineal Axis Tested in Patients Undergoing an Abdominal Hysterectomy

Tatsch-Dias¹,

Levandovski

Souza³

et al. 2013

Neuroimmunomodulation

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Objective: Activation of the immune-pineal axis induces a transient reduction in nocturnal melatonin in the plasma during the proinflammatory phase of an innate immune response to allow the proper migration of leukocytes to the lesion site. This transient reduction should be regulated by inflammatory mediators, which are responsible for the fine-tuning of the process. In the present study, we measured the pre- and postoperative serum concentrations of melatonin, tumor necrosis factor (TNF) and cortisol in women who underwent an elective hysterectomy and correlated the variation in melatonin with postoperative pain. Methods: We evaluated 12 women who had an abdominal hysterectomy. Blood was collected at 10.00 and 22.00 h 1 week and 1 day before the surgery, on the 1st and 2nd days after the surgery and at 22.00 h on the day of the surgery. Results: On the night after the surgery, there was no melatonin detected at 22.00 h. High TNF levels were accompanied by a lower nocturnal melatonin output, higher postoperative pain according to a visual analog scale and the request of higher doses of analgesics. In addition, low cortisol levels were accompanied by a lower nocturnal melatonin output. Conclusion: Our results confirm that the same antagonistic pattern between TNF and glucocorticoids observed in cultured pineal glands also occurs in humans. This integrative pattern suggests that the cross talk between the immune and endocrine system orchestrates longitudinal changes in pineal activity, reinforcing the hypothesis of an immune-pineal axis.

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Section: Discussionsupporting

confidence: 55%

Section: Introductionmentioning

confidence: 99%

The Concept of the Immune-Pineal Axis Tested in Patients Undergoing an Abdominal Hysterectomy

Tatsch-Dias¹,

Levandovski

Souza³

et al. 2013

Neuroimmunomodulation

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“…Regarding the study protocol, we have previously observed antinociceptive effects of melatonin in hot plate and Von Frey tests using the same protocol [16,17] and therefore chose these experimental models to test the effect of melatonin administration on BDNF levels. In addition, the melatonin doses chosen in the present study are in agreement with previous studies showing that the anti-inflammatory effects of melatonin starting at 10 mg/kg are less evident than those observed at lower doses [27], and with other studies showing an analgesic effect at higher doses [28,29].…”

Section: Discussionmentioning

confidence: 99%

“…The animals were randomly allocated to one of two groups (n = 7-8 per group): melatonin (treatment) or vehicle (control). Rats in the melatonin group were treated with intraperitoneal injections of melatonin (60 mg/kg, final solution 60 mg/ml), while those in the control group received vehicle (1% ethanol in saline) [16,18,19]. Treatment was administered 1 h after CFA injection and once daily for the subsequent 48 h (for a total of 3 days of melatonin administration), always at 3.00 p.m.…”

Section: Methodsmentioning

confidence: 99%

“…Additionally, previous studies performed by our research group have demonstrated an analgesic action of this indoleamine in acute [16] and chronic [17] complete Freund's adjuvant (CFA)-induced inflammation. Therefore, this study aimed to evaluate the effects of short- and long-term melatonin administration on central levels of BDNF in a rat model of acute and chronic inflammatory pain.…”

Section: Introductionmentioning

confidence: 99%

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Short- but Not Long-Term Melatonin Administration Reduces Central Levels of Brain-Derived Neurotrophic Factor in Rats with Inflammatory Pain

Laste

Rozisky²,

Caumo³

et al. 2015

Neuroimmunomodulation

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Objective: To evaluate the effect of short- and long-term administration of melatonin on central brain-derived neurotrophic factor (BDNF) levels in rats with acute and chronic inflammatory pain. Methods: The animals were allocated to one of two experiments: experiment 1 or experiment 2. In experiment 1, all animals were injected with complete Freund's adjuvant (CFA) to induce inflammation and were randomly allocated to receiving melatonin (60 mg/kg) or vehicle. Injections were administered 1 h after CFA and once daily for 2 more days (for a total of 3 days of melatonin administration). In experiment 2, fifteen days after CFA injection, the animals were treated with melatonin (50 mg/kg) or vehicle for 8 days. The animals were killed by decapitation 24 h after the last melatonin or vehicle administration, and an ELISA assay was performed to detect BDNF expression in the spinal cord, brainstem, and prefrontal cortex of the rats in both groups. Data were analyzed using Student's t test and the results are expressed as means ± SEM. Results: In the first experiment, the BDNF levels of the melatonin group were reduced in the prefrontal cortex (Student's t test, p = 0.01) and increased in the spinal cord (Student's t test, p = 0.04). In experiment 2, BDNF levels were similar in both groups for all structures (Student's t test, p > 0.00 for all). A two-way ANOVA reveled a significant effect of structures (p = 0.0001) but not of treatment (p > 0.05). The prefrontal cortex presented higher BDNF levels than other structures (ANOVA/Student-Newman-Keuls test, p = 0.0001). Considering the relationship between BDNF levels in all three structures, we found an effect of central nervous system structures (p = 0.01) and an interaction between treatment and structures (p = 0.04). Conclusion: The high spinal cord BDNF levels and the low prefrontal cortical BDNF levels observed in rats with acute CFA-induced inflammation following short-term melatonin administration may be related to the pain-modulating and neuroprotective effects of this protein. Long-term melatonin administration did not alter BDNF levels in chronic inflammation.

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Circadian dysfunction and Alzheimer's disease – An updated review

et al. 2022

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Alzheimer's disease (AD) is considered to be the most typical form of dementia that provokes irreversible cognitive impairment. Along with cognitive impairment, circadian rhythm dysfunction is a fundamental factor in aggravating AD. A link among circadian rhythms, sleep, and AD has been well‐documented. The etiopathogenesis of circadian system disruptions and AD serves some general characteristics that also open up the possibility of viewing them as a mutually reliant path. In this review, we have focused on different factors that are related to circadian rhythm dysfunction. The various pathogenic factors, such as amyloid‐beta, neurofibrillary tangles, oxidative stress, neuroinflammation, and circadian rhythm dysfunction may all contribute to AD. In this review, we also tried to focus on melatonin which is produced from the pineal gland and can be used to treat circadian dysfunction in AD. Aside from amyloid beta, tau pathology may have a notable influence on sleep. Conclusively, the center of this review is primarily based on the principal mechanistic complexities associated with circadian rhythm disruption, sleep deprivation, and AD, and it also emphasizes the potential therapeutic strategies to treat and prevent the progression of AD.

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Melatonin administration reduces inflammatory pain in rats

Cited by 17 publications

References 22 publications

The Concept of the Immune-Pineal Axis Tested in Patients Undergoing an Abdominal Hysterectomy

The Concept of the Immune-Pineal Axis Tested in Patients Undergoing an Abdominal Hysterectomy

Short- but Not Long-Term Melatonin Administration Reduces Central Levels of Brain-Derived Neurotrophic Factor in Rats with Inflammatory Pain

Circadian dysfunction and Alzheimer's disease – An updated review

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