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Are endocannabinoids the basis for neonatal analgesia through non-nutritive sucking?
  1. J Craske,
  2. M Cunliffe
  1. Pain and Sedation Service, Royal Liverpool Children’s Hospital, Alder Hey, Eaton Road, Liverpool, L12 2AP, UK
  1. Correspondence to:
    M Cunliffe
    Pain and Sedation Service, Royal Liverpool Children’s Hospital, Alder Hey, Eaton Road, Liverpool, L12 2AP, UK;

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The use of oral sucrose solution with and without non-nutritive sucking (NNS) has been shown to reduce the physiological and behavioural responses to procedural pain in neonates.1

The analgesic effects of sucrose are mediated by endogenous opioid pathways.1 In contrast, the analgesic effects of NNS are unknown but hypothesised to be through non-opioid pathways by stimulation of orotactile and mechanoreceptor mechanisms. We would like to propose that the mechanism underlying NNS is the endocannabinoid system.

Endocannabinoids are involved in pain modulation.2 Anandamide (ananda is the Sanskrit word for “bliss”) is an endogenous cannabinoid which binds to the cannabinoid CB1 receptor.3 Anandamides have a rapid onset but short duration of action.3 Cannabinoid CB1 receptors are present in pain processing areas of the brain and spinal cord. Their presence at nerve endings suggests they act as presynaptic modulators of neurotransmission.2 Endocannabinoids are believed to produce analgesia by descending modulation, by a direct spinal action, and by an action on the peripheral nerve.2

Endocannabinoids from the brain are required to initiate the suckling response.3 A newborn’s instinctive suckling behaviour seems to be dependent on the presence of anandamide. During a procedure, pain itself will also stimulate the release of anandamide, which may then act on cannabinoid receptors to attenuate nociception.2

It has been shown that the combination of sucrose and NNS appears to be more effective than sucrose or NNS alone.1 The proposed involvement of anandamides in NNS suggests that the calming combination of sucrose and NNS, utilising both the opioid and cannabinoid pathways, may be synergistic. This synergistic interaction is supported by evidence in the literature.4

Endogenous cannabinoids are involved in both pain modulation and the newborn’s suckling response. Further research is needed to clarify the role of endocannabinoids in neonatal procedural pain management through non-nutritive sucking.



  • Competing interests: none declared