Introduction: Endogenous morphine-like compounds have been identified in humans, and are released in response to stress. Human monocytes and granulocytes express the µ opiate receptor, µ3 which is morphine selective but opiate peptide insensitive(1). Recent studies have shown that CYP2D6 acts at critical steps for morphine biosynthesis (1). We theorized that ultra-rapid (UM) CYP2D6 metabolizers may have an enhancement of their endogenous pain modulating mechanisms.

Methods: IRB approval and signed informed consent were obtained. Morphine consumption was evaluated in the 4 h postoperative period in 141 female patients undergoing a standardized general anesthetic. The study group was divided, based on morphine consumption, into two sub-groups: low morphine consumers (LMC) (<=10 mg/4 h, n = 80) and high morphine consumers (HMC) (>10 mg/4 h, n=61). DNA was extracted from blood in all patients and was genotyped by the Amplichip® (Roche) to determine the specific CYP2D6 genotypes.

Results: UM were found to occur more frequently in the LMC group than the HMC (8 vs. 0, p=0.0019). No significant differences were noted for the Poor (PM), Intermediate (IM) or Extensive (EM) metabolizers.

Table 1.
	4 hrs cumulative morphine≤10 mg		4 hrs cumulative morphine > 10 mg		P value
CYP2D6	n=80		n=61
EM	55	68.75%	49	80.32%	0.1215
IM	13	16.25%	10	16.39%	0.9813
PM	4	5.0%	2	3.28%	0.6982
UM*	8	10.0%	0	0.00%	0.0091*

Discussion: Animal studies have suggested that endogenous morphine is involved in pain modulation (2). Human studies have demonstrated that CYP2D6 poor metabolizers may be less tolerant to tonic pain than extensive metabolizers. (3) Our current results suggest that ultrarapid metabolizers may have higher efficiency in synthesizing endogenous morphine compared to other metabolizers, thus increasing endogenous pain modulation and reducing the need for exogenous morphine.