title: Age-dependency of analgesia elicited by intraoral sucrose in acute and persistent pain models.
abstract: Treatment of pain in newborns is associated with problematic drug side effects. Previous studies demonstrate that an intraoral infusion of sucrose and other sweet components of mother's milk are effective in alleviating pain in infant rats and humans. These findings are of considerable significance, as sweet tastants are used in pain and stress management in a number of clinical procedures performed in human infants. The ability of sweet stimuli to induce analgesia is absent in adult rats, suggesting that this is a developmentally transient phenomenon. However, the age range over which intraoral sucrose is capable of producing analgesia is not known. We investigated the effects of intraoral sucrose (7.5%) on nocifensive withdrawal responses to thermal and mechanical stimuli in naive and inflamed rats at postnatal days (P) P0-21. In some rats, Complete Freund's adjuvant (CFA) was injected in a fore- or hindpaw to produce inflammation. In non-inflamed animals, for noxious thermal stimuli, sucrose-induced analgesia emerged at P3, peaked at P7-10, then progressively declined and was absent at P17. For mechanical forepaw stimuli, sucrose-induced analgesia emerged, and was maximal at approximately P10, then declined and was absent at P17. By contrast, maximal sucrose-induced analgesia for mechanical hindpaw stimuli was delayed (P13) compared to that for the forepaw, although it was also absent at P17. In inflamed animals, sucrose reduced hyperesthesia and hyperalgesia assessed with mechanical stimuli. Sucrose-induced analgesia in inflamed animals was initially present at P3 for the forepaw and P13 for the hindpaw, and was absent by P17 for both limbs. Intraoral sucrose produced significantly greater effects on responses in fore- and hindpaws in inflamed rats than in naive rats indicating that it reduces hyperalgesia and allodynia beyond its effects on responses in naive animals. These findings support the hypothesis that sucrose has a selective influence on analgesic mechanisms and that an enhanced sucrose effect takes place in hyperalgesic, inflamed animals as compared to naive animals. Taken together, these results indicate that intraoral sucrose alleviates transient pain in response to thermal and mechanical stimuli, and also effectively reduces inflammatory hyperalgesia and allodynia. Sucrose-induced analgesia is age-dependent and limited to the pre-weaning period in rats. The age-dependency of sucrose-induced analgesia and its differential maturation for the fore- and hindpaw may be due to developmental changes in endogenous analgesic mechanisms and developmental modulation of the interaction between gustatory and pain modulatory pathways.
authors.affiliation: Department of Anatomy and Neurobiology, Program in Neuroscience, University of Maryland School of Medicine, Baltimore 21201, USA. vanse001@umaryland.edu
authors.forename: Vanessa C Z
authors.initials: VC
authors.lastname: Anseloni
authors.forename: H-R
authors.initials: HR
authors.lastname: Weng
authors.forename: R
authors.initials: R
authors.lastname: Terayama
authors.forename: David
authors.initials: D
authors.lastname: Letizia
authors.forename: Barry J
authors.initials: BJ
authors.lastname: Davis
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
authors.forename: Matthew
authors.initials: M
authors.lastname: Ennis
mesh_terms: D000208:Acute Disease; D000284:Administration, Oral; D000367:Age Factors; D000698:Analgesia / Q000379:methods*; D000818:Animals; D000831:Animals, Newborn; D002908:Chronic Disease; D004195:Disease Models, Animal; D006358:Hot Temperature; D010146:Pain / Q000188:drug therapy*; D017288:Pain Threshold / Q000187:drug effects; D051381:Rats; D017207:Rats, Sprague-Dawley; D011957:Receptors, Opioid / Q000502:physiology; D013395:Sucrose / Q000494:pharmacology*; D013649:Taste / Q000502:physiology*
chemical_list: D011957:Receptors, Opioid; D013395:Sucrose