Suspected
            <scp>opioid‐induced</scp>
            hyperalgesia in an infant following surgery: A case report

Efune, Proshad N.; Rebstock, Sarah

doi:10.1111/jcpt.13756

Cited by 3 publications

(1 citation statement)

References 39 publications

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“…Chronic use of BUP has been reported to cause hyperalgesia resulting in exacerbation of pain sensation rather than its relief (Athanasos et al, 2019; Larson et al, 2020; Mercadante et al, 2019). Although opioid-induced hyperalgesia is generally associated with opioid use by adults, evidence of opioid-induced hyperalgesia in infants (Efune and Rebstock, 2022; Hallett and Chalkiadis, 2012; Zissen et al, 2007) has been reported and is a potentially under-recognized phenomenon due to difficulty distinguishing whether signs of pain and discomfort in non-verbal infants are due to opioid-induced hyperalgesia or inadequate pain management that is possibly caused by tolerance. Hyperalgesia is a symptom of opioid withdrawal, further complicating distinction between BUP-induced hyperalgesia and withdrawal in the neonatal human or rat.…”

Section: Discussionmentioning

confidence: 99%

Interaction between buprenorphine and norbuprenorphine in neonatal opioid withdrawal syndrome.

Tobacyk

Parks

Salazar

et al. 2022

Preprint

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Buprenorphine (BUP) is the preferred treatment for opioid use disorder during pregnancy but can cause neonatal opioid withdrawal syndrome (NOWS). Norbuprenorphine (NorBUP), an active metabolite of BUP, is implicated in BUP-associated NOWS. We hypothesized that BUP, a low-efficacy agonist of mu opioid receptors, will not antagonize NorBUP, a high-efficacy agonist of mu opioid receptors, in producing NOWS. To test this hypothesis, we treated pregnant Long-Evans rats with BUP (0, 0.01, 0.1 or 1 mg/kg/day) ± NorBUP (1 mg/kg/day) from gestation day 9 until pup delivery, and tested pups for opioid dependence using our established NOWS model. We used LC-MS-MS to quantify brain concentrations of BUP, NorBUP, and their glucuronide conjugates. BUP had little effect on NorBUP-induced NOWS, with the exception of 1 mg/kg/day BUP significantly increasing NorBUP-induced NOWS by 58% in females. BUP and NorBUP brain concentrations predicted NOWS in multiple linear regression models. Interestingly, NorBUP contributed more to NOWS in females (βNorBUP= 51.34, p = 0.0001) than in males (βNorBUP= 19.21, P = 0.093), while BUP was similar for females (βBUP= 10.62, P = 0.0017) and males (βBUP= 11.38, P = 0.009). We are the first to report that NorBUP induces NOWS in the presence of BUP and that there is sexual divergence in the contribution of NorBUP to BUP-associated NOWS. These findings suggest that females are more susceptible to NorBUP-induced NOWS, and that treatment strategies that reduce prenatal NorBUP exposure may be more effective for females than males.

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