Massive opioid resistance in an infant with a localized metastasis to the midbrain periaqueductal gray.

We report the case of a 4-month-old infant with terminal malignancy who had systemic metastases and a localized metastasis to the dorsal midbrain periaqueductal gray (PAG). Extraordinary doses of opioids (dose equivalent of 2680 mg morphine sulfate/h, i.v.) were required to achieve adequate analgesia. The behavior of the infant, interpreted as being representative of a response to pain, may have been an aversive reaction due to the location of the lesion in the dorsal PAG. We propose that the lesion in the PAG impaired the responsiveness of this infant to the effect of opioids. This report is to alert clinicians to the possible role of the PAG in impaired opioid responsiveness in patients with terminal malignancy, as well as the possibility that pain-like signs (e.g., tachycardia, tachypnea, vocalization, facial grimacing) may indicate an aversive reaction rather than pain in non-verbal patients.