Antinociceptive effects of melatonin in a rat model of post-inflammatory visceral hyperalgesia: a centrally mediated process. Pain 2010 Jun;149(3):555-564
Date
04/24/2010Pubmed ID
20413219Pubmed Central ID
PMC2884285DOI
10.1016/j.pain.2010.03.030Scopus ID
2-s2.0-77952109906 (requires institutional sign-in at Scopus site) 37 CitationsAbstract
Previous reports suggest that melatonin may play an important role in visceral nociception and neurogenic inflammation. We aimed to examine the role of melatonin on visceral hypersensitivity and to explore the site of action using a rat model of post-inflammatory visceral hyperalgesia. In all rats, a baseline viscero-motor response (VMR) to graded colorectal distension (CRD; 10-60mmHg) was recorded prior and 1 week following tri-nitrobenzenesulfonic acid (TNBS) induced colonic inflammation. Melatonin (30, 45 or 60mg/kg, ip) was given 20min before testing the VMR in naïve and TNBS-treated rats. Extracellular single-unit recordings were made from CRD-sensitive pelvic nerve afferent (PNA) fibers and lumbosacral (LS) spinal neurons in TNBS-treated animals. The effect of melatonin (60mg/kg) was examined on responses of PNAs and spinal neurons to graded CRD. In separate experiments, luzindole (non-specific MT(1)/MT(2) receptor antagonist) or naltrexone (non-specific opiod receptor antagonist) was injected prior to melatonin. Following TNBS, there was a significant increase in the VMR to CRD compared to baseline. This increase was attenuated by melatonin (60mg/kg) at pressures >20mmHg. The same dose of melatonin had no effect on the VMR in naïve animals. In TNBS-treated rats, melatonin significantly attenuated the responses of CRD-sensitive spinal neurons to CRD, but had no effect in spinal transected rats or PNA fibers. Both luzindole and naltrexone blocked melatonin's effect on the VMR and LS spinal neurons. Results indicate melatonin's antinociceptive effects are not via a peripheral site of action but rather a supra-spinal process linked to the central opioidergic system.
Author List
Mickle A, Sood M, Zhang Z, Shahmohammadi G, Sengupta JN, Miranda AAuthors
Adrian Miranda MD Adjunct Professor in the Pediatrics department at Medical College of WisconsinJyoti N. Sengupta PhD Professor in the Medicine department at Medical College of Wisconsin
MESH terms used to index this publication - Major topics in bold
AnalgesicsAnimals
Colitis
Disease Models, Animal
Hyperalgesia
Inflammation
Male
Melatonin
Narcotic Antagonists
Rats
Rats, Sprague-Dawley
Receptors, Melatonin
Tryptamines
Visceral Afferents
