Pain is bad for you, sucrose makes it better (even if you are a rat).

I rarely discuss animal research in this blog, but occasionally something striking stimulates a new post.

I have discussed sucrose not that long ago, in particular I emphasized the over-interpretation of a secondary analysis of a non-randomized comparison of very early follow up data from an RCT of the use of sucrose as an analgesic. I will quote myself as I think I am worth quoting:

I am taking this long excursion into the results of an older study because it has been quoted many times as perhaps showing an adverse effect of sucrose on what is often referred to as “neurodevelopmental outcome”. So lets be completely clear, on secondary analysis of a small RCT, data from 2/3 of the preterm babies enrolled showed a statistically significant correlation between the number of sucrose doses given and one item of the 7 items of the NAPI at 40 weeks PMA.

I emphasize that the randomized comparison in that trial showed no difference on any of those items.

Sucrose is an effective analgesic, with no known toxicities. Long term outcome effects are “uncertain” according to the latest Cochrane review. It is difficult to believe that recurrent use of tiny quantities of sucrose would be harmful in the long term, but I guess we need to be cautious with preterm babies.

We can be a lot less cautious with rats.

In this study rats were divided at birth to receive either chronic pain, with a needle stuck into a foot paw 4 times a day for 8 weeks (sounds like being in the NICU), or they got sucrose 4 times a day, or they got the foot pricks but they were preceded by sucrose, or they got a dose of paracetamol then the foot pricks (there was also a non-foot prick no analgesia control group). The sucrose was given on the rats’ tongues so they experienced the sweetness, just like our babies.

The rats that got the foot pricks without analgesia had impaired short term memory when they were tested as adults. Sucrose prevented the decline associated with repeated pain.

Sucrose had no effect on its own, without the pain. The sucrose groups had higher endorphins in the blood. The authors also dissected out the hippocampus on the rats and measured some neurotrophic factors including brain-derived neurotrophic factor BDNF.

…results of the current study showed a significant decrease in BDNF levels in the hippocampus of chronic pain exposed animals. Sucrose treatment, on the other hand, normalized this decline in BDNF levels.

Which gives some idea of possible mechanisms, the endorphin link has been seen before, I believe, but I am new to the BDNF stuff, it sounds like this is a novel finding, but it seems to link up with other research that the authors quote. It certainly looks like BDNF is important for developing learning and memory formation.

There has never been any evidence that sucrose adversely effects human long term outcomes, on the other hand there is substantial evidence that pain does. Although this is a rat study, it does suggest that there is a chance that effective analgesia, using sucrose, will decrease those adverse effects. Even with 4 doses a day for 8 weeks.

About keithbarrington

I am a neonatologist and clinical researcher at Sainte Justine University Health Center in Montréal
This entry was posted in Neonatal Research and tagged , , . Bookmark the permalink.

2 Responses to Pain is bad for you, sucrose makes it better (even if you are a rat).

  1. Arun Nair MD FRACP FRCPCH says:

    Thanks for the information about the link between sucrose and endorphin. It is important to realize that pain has different effects on a developing brain. Were these rats newborns?
    The biggest modulating effect of sucrose is still on the behavioural aspects- in the newly borns, it probably suppresses the CVS and Respiratory response mostly by its effect on the brain stem. What about its function on the cortical and subcortical areas, where chronic & recurrent pain has shown to produce adverse effects?

  2. Thank you for bringing to research to the public and explaining it very nicely. As the PI, I would like people to know about studies like these because unfortunately hospitals and clinics do not employ this simple and non-pharmacological method to relief pain in neonates and young children.

    To answer Arun Nair MD FRACP FRCPCH, yes these were neonatal rats. Treatment started post-natal day one. This research shows that neuro-chemical do change in the hippocampus as evident in the changes in BDNF, ENK, beta-END.

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