Gene/Protein Disease Symptom Drug Enzyme Compound
Pivot Concepts:   Target Concepts:
Query: UMLS:C0184567 (acute pain)
 3,962 document(s) hit in 31,850,051 MEDLINE articles (0.00 seconds)

Evidence for a relationship between melatonin, nociception, and analgesia in humans is based on data that are only linked by association and simultaneous occurrence. Studies have reported inverse correlation of the circadian melatonin rhythm with nociception latency and enhancement of opioid analgesia by simultaneous administration of melatonin in animals. This study examines the response of salivary melatonin to acute pain stimuli in 18 healthy subjects ranging in age from 19 to 50 years. A biphasic melatonin response following an acute pain stimulus of 36 V was observed, F(8, 8) = 17.839, P < 0.001. Within 5 min of the stimulus, melatonin decreased and reached a plateau of 36 pg/mL below baseline by 20 min. This decrease was followed by an increase of 5 pg/mL. Melatonin levels subsequently decreased until they had reached levels similar to those anticipated for the time of day and did not vary thereafter. The magnitude of the melatonin response was not related to age or gender. There was no association between voltage and magnitude of the melatonin responses observed at 15 min (r =0.185, P=0.51) or at 30 min (r = 0.468, P = 0.09). This study provides the first evidence of melatonin utilization and subsequent pineal gland synthesis following acute pain episodes in humans.
 ...
PMID:Salivary melatonin response to acute pain stimuli. 1133 9

The occurrence of systematic diurnal variations in pain thresholds has been demonstrated in human. Salivary melatonin levels change following acute pain when other factors that could explain the change have been removed or controlled. Melatonin-induced analgesia is blocked by naloxone or pinealectomy. By using selective radioligands [3H]-DAMGO, [3H]-DPDPE, [3-U69593, and 3H]-nociceptin, we have shown that the bovine pinealocytes contain delta and mu, but not kappa or ORL1 opioid receptor subtypes. In the present study, by using melatonin receptor agonists (6-chloromelatonin or 2-iodo-N-butanoyl-5-methoxytryptamine) or melatonin receptor antagonist (2-phenylmelatonin), we have shown that these agents do not compete with opioid receptor subtypes. However, we observed a time-dependent release of beta-endorphin an endogenous opioid peptide, by melatonin from mouse pituitary cells in culture. Hence, it is suggested that melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by binding to its own receptors and increasing the release of beta-endorphin.
 ...
PMID:Melatonin exerts its analgesic actions not by binding to opioid receptor subtypes but by increasing the release of beta-endorphin an endogenous opioid. 1563 42

Melatonin is a remarkable molecule with diverse physiological functions. Some of its effects are mediated by receptors while other, like cytoprotection, seem to depend on direct and indirect scavenging of free radicals not involving receptors. Among melatonin's many effects, its antinociceptive actions have attracted attention. When given orally, intraperitoneally, locally, intrathecally or through intracerebroventricular routes, melatonin exerts antinociceptive and antiallodynic actions in a variety of animal models. These effects have been demonstrated in animal models of acute pain like the tail-flick test, formalin test or endotoxin-induced hyperalgesia as well as in models of neuropathic pain like nerve ligation. Glutamate, gamma-aminobutyric acid, and particularly, opioid neurotransmission have been demonstrated to be involved in melatonin's analgesia. Results using melatonin receptor antagonists support the participation of melatonin receptors in melatonin's analgesia. However, discrepancies between the affinity of the receptors and the very high doses of melatonin needed to cause effects in vivo raise doubts about the uniqueness of that physiopathological interpretation. Indeed, melatonin could play a role in pain through several alternative mechanisms including free radicals scavenging or nitric oxide synthase inhibition. The use of melatonin analogs like the MT(1)/MT(2) agonist ramelteon, which lacks free radical scavenging activity, could be useful to unravel the mechanism of action of melatonin in analgesia. Melatonin has a promising role as an analgesic drug that could be used for alleviating pain associated with cancer, headache or surgical procedures.
 ...
PMID:Potential use of melatonergic drugs in analgesia: mechanisms of action. 2000 25