Analgesic effects on endogenous melatonin secretion

Abstract

Animal welfare concerns have led to increased demands for use of post-operative analgesia in association with experimental surgery. Such treatment is appropriate provided it has no effect on experimental parameters. In order to assess any effects of analgesics on endogenous melatonin production, groups of six ewes were bled at 30 min intervals for the first 4 hr of darkness a) without analgesic treatment and b) immediately after analgesic administration. Analgesics tested were ketoprofen, phenylbutazone (both non-steroidal anti-inflammatory drugs or NSAIDs) and buprenorphine (an opioid). Plasma melatonin was measured by radioimmunoassay and 4 hr secretion profiles computed for each animal. Ketoprofen and buprenorphine treatment reduced mean four hour melatonin secretion profiles by 50.6% (from 1,347.3 to 665.1 pg/ml.hr) and 38.6% (from 287.8 to 171.3 pg/ml.hr), respectively. Only in the case of phenylbutazone was the response not statistically significant; hence this drug has been selected as a post-operative analgesic for future experimental studies involving measurement of melatonin levels.

The Healthy Heart-Mind trial: melatonin for prevention of delirium following cardiac surgery: study protocol for a randomized controlled trial

“…In addition, older people are more prone to sleep disorders arising from degeneration of suprachiasmatic nuclei and resulting lower melatonin levels [ 22 ]. Serum melatonin levels decrease post surgery [ 23 ] and after the administration of certain opioids [ 24 ], possibly contributing to the disrupted sleep-wake cycle and increased risk of delirium that these patients experience. Plasma melatonin levels have been shown to be lower in delirious patients following major surgery [ 25 ] and urine concentrations of melatonin metabolites are altered in people who are delirious [ 26 ].…”

Melatonin or Ramelteon for Delirium Prevention in the Intensive Care Unit: A Systematic Review and Meta-Analysis of Randomized Controlled Trials

“…The idea to use melatonin in critically ill patients is based on the greater risk of development of delirium in this population of patients due to the greater severity of their clinical conditions and the characteristics of the ICU in terms of the noisy environment and alteration of the day–night cycle [ 32 , 33 , 34 ]. There is evidence of very low melatonin levels in critically ill patients [ 33 , 35 , 36 , 37 , 38 , 39 , 40 ]; thus, it is theoretically reasonable to expect greater effects of melatonin in this setting.…”

Oxidative Stress in Relation to Surgery: Is There a Role for the Antioxidant Melatonin?

“…The pathophysiological mechanism behind a disturbed circadian rhythm of melatonin secretion is not known. Factors such as magnitude of surgery [12,48], anesthesia [64], perioperative administration of certain drugs (benzodiazepines [65], ␤-blockers [66], calcium channel blockers [67], nonsteroidal anti-inflammatory drugs [68], and dexamethasone), nocturnal light [69 -71], hepatic metabolism, activation of the hypothalamo-pituitary-adrenal axis [72,73], and use of opioid analgesics [74] may all affect postoperative melatonin secretion. Whether reduced endogenous secretion of melatonin after surgery has a negative effect on the oxidative status and results in increased morbidity remains to be investigated.…”