Table 4.

Overview of studies that investigated the COMT Val158Met polymorphism in relation to pain sensitivity

Study design	Study population	Intervention	Main outcome	Reference
Experimental	29 healthy volunteers	Binding potential of the μ receptor and muscle pain was measured twice: during intensity-controlled sustained pain induced by infusion of 5% hypertonic saline into the masseter muscle and during the infusion of nonpainful 0.9% isotonic saline.	Subjects with the Met/Met genotype of the COMT Val158Met polymorphism showed diminished regional μ-opioid system responses to pain compared with Met/Val and Val/Val subjects. These effects were accompanied by higher sensory and affective ratings of pain.	15
Experimental	202 female healthy volunteers	Threshold and tolerance to thermal, ischaemic and mechanical stimuli, as well as temporal summation to heat pain, were determined.	The Val158Met polymorphism was associated with sensitivity to painful heat stimuli, which suggests that the Val158Met polymorphism plays a primary role in variation in temporal summation of pain.	16
Experimental	43 healthy volunteers	Five applications of thermal heat pain were made to the hand. After each stimulus, subjects rated pain on a VAS. Before the second and the fourth stimulus, respectively, an intravenous injection of remifentanil (0.08 mg kg−1) and placebo was administered.	Met/Met subjects reported significantly more pain compared with Val/Val subjects in the case of repeated pain stimuli, although not during an initial response of the descending pain system. The opioid intervention induced analgesia without a separating effect for genotype.	17
Experimental	54 healthy volunteers	Subjects received two heat pain stimuli on the right forearm during functional magnetic resonance imaging. After each stimulus, subjects rated their pain intensity using the Gracely Sensory Scale.	Met/Met subjects showed stronger pain-related functional magnetic resonance imaging signals than Val/Val subjects in several brain structures, only for high-intensity pain stimuli after repeated administration.	29
Experimental	500 healthy volunteers	Subjects received a painful thermal and cold stimulus, measured on the hand up to the wrist, with VAS ratings and temperature dimensions of personality. In total, three single nucleotide polymorphisms were evaluated.	In a classification and regression tree analysis, the Val158Met polymorphism did not provide a strong predictive value for heat or cold pain sensitivity.	33
Clinical research design	207 patients treated with morphine for chronic cancer pain	Between the genotype groups, morphine doses, serum concentrations of morphine and morphine metabolites were compared.	After a mean treatment period of 3.5 months, patients with the Val/Val genotype needed more morphine when compared with the Val/Met and the Met/Met genotype groups. Pain scores were not reported.	9
Clinical research design	221 acute postsurgical patients	Clinically induced pain was recorded using the VAS after oral surgery every 20 min until subjects requested analgesic medication (ketorolac), followed by VAS scores at 15 min intervals for 180 min.	Although the COMT enzyme showed significant associations with the maximal postoperative pain, this association was not sustained after correcting for multiple comparisons.	31
Clinical research design	2294 cancer patients	Among other things, pain intensity, time on opiods and 112 single nucleotide polymorphisms that may predict opioid dose were included as covariates in a regression model.	None of the 112 single nucleotide polymorphisms showed significant associations with opioid dose.	32

Abbreviations are as follows: COMT, catechol-O-methyltransferase; and VAS, visual analog scale, range 0–10.