Methadone effectively attenuates acute and long-term consequences of neonatal repetitive procedural pain in a rat model

Background
Painful procedures in early life cause acute pain and can alter pain processing at a spinal level lasting into adulthood. Current methods of analgesia seem unable to prevent both acute and long-term hypersensitivity associated with neonatal pain. The current study aims to prevent acute and long-term hypersensitivity associated with neonatal procedural pain using methadone analgesia in rat pups.

Methods
Sprague–Dawley rat pups received either methadone (1 mg/kg) or saline prior to repetitive needle pricks into the left hind paw from the day of birth (postnatal day (P)0) to P7. Control littermates received a tactile stimulus. Mechanical sensitivity was assessed during the neonatal period (P0–P7), from weaning to adulthood (3–7 weeks) and following surgical re-injury of the same dermatome in adulthood.

Results
Methadone administration completely reversed acute hypersensitivity from P0 to P7. In addition, neonatal methadone analgesia prevented prolonged hypersensitivity after re-injury in adulthood, without affecting sensitivity from weaning to adulthood.

Conclusions
The current study shows that neonatal methadone analgesia can attenuate acute as well as long-term hypersensitivity associated with neonatal procedural pain in a rat model.

Impact
Methadone treatment attenuates acute and long-term hypersensitivity associated with neonatal pain in a rat model.

Clinical effectiveness studies are urgently warranted to assess acute and long-term analgesic effectivity of methadone.