Does neonatal surgery lead to increased pain sensitivity in later childhood?

Abstract

Does pain or tissue damage in early life lead to hyperalgesia persisting into childhood? We performed a cross-sectional study in 164 infants to investigate whether major surgery within the first 3 months of life increases pain sensitivity to subsequent surgery and to elucidate whether subsequent surgery in the same dermatome or in a different dermatome leads to differences in pain sensitivity. All infants received standard intraoperative and postoperative pain management, with rescue analgesia guided by a treatment algorithm. Differences in pain sensitivity during surgery were assessed by the intraoperative fentanyl intake and by (nor)epinephrine plasma concentrations. Differences in postoperative pain sensitivity were assessed by the observational pain measures COMFORT and VAS, and by morphine intake and (nor)epinephrine plasma concentrations. Infants previously operated upon in the same dermatome needed more intraoperative fentanyl, had higher COMFORT and VAS scores, had greater (nor)epinephrine plasma concentrations, and needed also more morphine than did infants with no prior surgery. In contrast, infants who previously underwent surgery in another dermatome had only significant higher postoperative analgesic requirements and norepinephrine plasma concentrations in comparison with infants with no prior surgery. These preliminary differences may indicate the occurrence of spinal and supraspinal changes following neonatal surgery. We conclude that the long-term consequences of surgery in early infancy are greater in areas of prior tissue damage and that these effects may portend limited clinical but important neurobiological differences.

Use of Analgesic and Sedative Drugs in the NICU: Integrating Clinical Trials and Laboratory Data

“…Remifentanil decreased pain for PICC insertion (169) Thoracic rigidity requiring muscle blocker injection (alfentanil 20 g/kg) (167). Same time to complete the maneuver and procedure time as placebo (169) Acetaminophen Ն37 wks GA No effect for heel lance (170) Good hepatic tolerance (149) Ketamine Ineffective for tracheal suctioning (125) No cerebral hemodynamic adverse effect (5 mg/kg) (124) Repetitive painful stimuli may persistently alter pain processing in humans (171), and epidemiologic studies have revealed an association between peri-and neonatal complications and behavioral/emotional problems in childhood, anxiety/ depression, and even suicidal tendencies (172,173). Conversely, drug toxicity should not be underestimated and risk/ benefit balance must be evaluated when prescribing analgesia or sedation for neonates.…”

Pharmacological approaches to the management of pain in the neonatal intensive care unit

“…The repetitive stimulation of the pain system may attenuate peripheral sensitivity or decrease behavioral responses resulting in altered development. [8][9][10] The three categories of pain (acute, established, or prolonged) based on their duration will result in different clinical manifestations. Most pain studies in neonates have studied models of acute pain, heel sticks or circumcision, two of the most common invasive procedures performed in neonates.…”

Ketamine Reduces the Cell Death Following Inflammatory Pain in Newborn Rat Brain

“…Adverse experiences during early development alter neuronal activity patterns and may permanently alter the functional wiring of immature neurons. Epidemiologic associations occur relating perinatal or neonatal complications with behavioral and emotional problems in childhood (2), altered pain responses (1,3,4), anxiety, depression (2,5), or suicidal tendencies (6,7).…”

“…Repetitive neonatal pain persistently alters pain processing, in rats (11), mice (12), and humans (3,4), and glucocorticoid responses in older infants (13). Conversely, prolonged treatment of infant rats with high doses of analgesic or anesthetic agents triggers widespread neurodegeneration in their brain (14).…”