**6. Conclusion**

sucrose-induced analgesia is age-dependent that means it occurs mainly during the pre-

Artificial sweeteners have also shown analgesic actions when administered orally. Chronic saccharin intake decreases pain sensitivity and increases pain threshold as measured in hotplate test [60]. Furthermore, acute saccharin administration for 5 hours resulted in analgesia that persists for 3 hours [61]. Aspartame, another sweetener, decreases pain sensitivity, and

Although the mechanisms behind sweet substances-induced analgesia are still not clearly defined; endogenous opioid system is implicated. Sweet palatable solutions augment morphine-induced analgesia [64–67], this has suggested that sweet solutions ingestion is associated with the release of endogenous opioids, a mechanism which involves stimulation of gustatory sweet receptors [68]. This mechanism was supported by the observation that sucrose reduces pain sensation when administered orally not when applied via gastric gavage [12, 69]. Furthermore, naltrexone and naloxone, opioid antagonists, were shown to abolish the analgesic effect of sweet-tasting solutions [56, 70–72] In addition, consuming palatable sweet substances increases endogenous β-endorphin activity in rat brain and in human plasma [69, 73–75]. Besides, endogenous opioid system, other neurotransmitters and receptors are probably involved. One study revealed a major involvement of nicotinic cholinergic receptors in the sweet substanceinduced analgesia as atropine (cholinergic antagonist) diminished sucrose-induced analgesia [76]. Other studies have shown the involvement of noradrenaline, serotonin and their recep-

Likewise, sweet solutions ability to prevent, decrease or reverse unfavorable long-term effects of neonatal pain had been explored. Unpublished data and a previous study from our lab indicate that early pain experience increases pain sensitivity and impairs spatial memory during adulthood in rats; the interventions using sucrose or saccharin solution prevented these

**5. Short- and long-term effects of using sweet solutions during infancy**

The fear of adverse effects following the use of nutritive sweet solutions for analgesia for premature and mature infants might be a hindrance to implementing this analgesic method. Among possible short-term effects are the fear of effect of sweet intake on milk feeding afterward. Also the effect on body weight, weather an increase due to development of sweet tooth or a decrease due to decrease in appetite for healthy food such as milk. Of the long-term effects are potential negative effects on growth and development. Of more concern would be the neurodevelopmental deficits, such as attention/orientation and motor tasks, that might result of higher intake of sugar during infancy, particularly infants who spend lengthier time at the NICU and are exposed to multiple painful procedures daily, thus requiring several doses of sweet solutions. It has been calculated that the amount of sugar a preterm infant will ingest over a period of a few weeks at the NICU will be equivalent to half a can of coke ingested by a 1-year-old [48]. Since few studies have examined the potential adverse effects

has shown to produce analgesic effects comparable with sucrose [62, 63].

tors in the central modulation sweet substance-induced analgesia [71, 77, 78].

long-term consequences of neonatal pain [75].

weaning period in rats [57].

306 Pain Relief - From Analgesics to Alternative Therapies

Pain due to procedures applied to premature infants has shown to affect, in a negative way, brain development. Newborns, particularly premature infants have brains and nervous systems that are still under development and are very vulnerable to any insults. The plasticity of the brain at this early age makes it ideal for external stimuli to have long lasting effects [1]. Thus it is logical to put forward the hypothesis that managing this pain will in addition to its pain reducing effects be useful in inhibiting or at least reducing the long term unfavorable effects of untreated pain.

Despite availability of analgesia and knowledge about infants' pain, a gap still exists between theoretical knowledge and actual practice. Thus the availability of non-pharmacological analgesia is very important and might be the selling point for the use of analgesia for premature and mature infants [4].

In conclusion, using sweet solutions for pain management, particularly, for this special age group is probably effective and safe, and has the potential of reversing or decreasing longterm adverse effects of pain. More studies need to be done to further explore the safety and the dose of sweet solution for pain during infancy.
