Pineal opioid receptors and analgesic action of melatonin

Abstract

Physicians have noted since antiquity that their patients complained of less pain and required fewer analgesics at night times. In most species, including the humans, the circulating levels of melatonin, a substance with analgesic and hypnotic properties, exhibit a pronounced circadian rhythm with serum levels being high at night and very low during day times. Moreover, melatonin exhibits maximal analgesic effects at night, pinealectomy abolishes the analgesic effects of melatonin, and mu opioid receptor antagonists disrupt the day-night rhythm of nociception. It is believed that melatonin, with its sedative and analgesic effects, is capable of providing a pain free sleep so that the body may recuperate and restore itself to function again at its peak capacity. Moreover, in conditions when pain is associated with extensive tissue injury, melatonin's ability to scavenge free radicals and abort oxidative stress is yet another beneficial effect to be realized. Since melatonin may behave as a mixed opioid receptor agonist-antagonist, it is doubtful that a physician simply could potentiate the analgesic efficacy of narcotics such as morphine by coadministering melatonin. Therefore, future research may synthesize highly efficacious melatonin analogues capable of providing maximum analgesia and hopefully being devoid of addiction liability now associated with currently available narcotics.

Effects of preoperative oral melatonin medication on postoperative analgesia, sleep quality, and sedation in patients undergoing elective prostatectomy: a randomized clinical trial

“…Melatonin has been associated with pain relief in patients with tissue injuries [11] and possesses antiinflammatory effects [12]. Although several findings have fueled speculation that melatonin affects pain sensitivity via an opiatergic mechanism [13], it is conceivable that melatonin may modulate variations in pain perception by affecting the activity of b-endorphin [14].…”

Extremely low frequency magnetic field exposure modulates the diurnal rhythm of the pain threshold in mice

“…It has been shown that melatonin has analgesic effects through the opioid and benzodiazepine systems [Golombek et al, 1991;Ebadi et al, 1998;Jeong et al, 2000;Yu et al, 2000]. In most species, melatonin displays a circadian pattern with maximal level at night [Tamarkin et al, 1985].…”

Metabolic Effects of Prolonged Melatonin Administration and Short-Term Fasting in Laboratory Rats

“…Receptors or high affinity MEL binding sites were found in many tissues, indicating that MEL regulates physiological functions through a direct effect on these tissues. MEL synchronizes biological rhythms and exerts antioxidant (Tan et al 1993ab) and oncostatic (Hill and Blask 1988) properties; sedative, immunomodulative, analgetic, myorelaxing, cardioprotective and neuroprotective effects have been reported (Maestroni 1993;Reiter et al 1998;Lagneux et al 2000;Ebadi et al 1998;Vijayalaxmi et al 2002).…”