Association between UGT2B7 gene polymorphisms and fentanyl sensitivity in patients undergoing painful orthognathic surgery.

Background Fentanyl is often used instead of morphine for the treatment of pain because it has fewer side effects. The metabolism of morphine by glucuronidation is known to be influenced by polymorphisms of the UGT2B7 gene. Some metabolic products of fentanyl are reportedly metabolized by glucuronate conjugation. The genes that are involved in the metabolic pathway of fentanyl may also influence fentanyl sensitivity. We analyzed associations between fentanyl sensitivity and polymorphisms of the UGT2B7 gene to clarify the hereditary determinants of individual differences in fentanyl sensitivity. Results This study examined whether single-nucleotide polymorphisms (SNPs) of the UGT2B7 gene affect cold pain sensitivity and the analgesic effects of fentanyl, evaluated by a standardized pain test and fentanyl requirements in healthy Japanese subjects who underwent uniform surgical procedures. The rs7439366 SNP of UGT2B7 is reportedly associated with the metabolism and analgesic effects of morphine. We found that this SNP is also associated with the analgesic effects of fentanyl in the cold pressor-induced pain test. It suggested that the C allele of the rs7439366 SNP may enhance analgesic efficacy. Two SNPs of UGT2B7, rs4587017 and rs1002849, were also found to be novel SNPs that may influence the analgesic effects of fentanyl in the cold pressor-induced pain test. Conclusions Fentanyl sensitivity for cold pressor-induced pain was associated with the rs7439366, rs4587017, and rs1002849 SNPs of the UGT2B7 gene. Our findings may provide valuable information for achieving satisfactory pain control and open to new avenues for personalized pain treatment.

Lack of temporal summation but distinct aftersensations to thermal stimulation in patients with combined tension-type headache and myofascial temporomandibular disorder.

AIMS: To compare patients with combined tension-type headache and myofascial temporomandibular disorder (TMD) with control subjects on two measures of central processing-ie, temporal summation and aftersensations to heat stimulation in the trigeminal nerve and spinal nerve territories. METHODS: A novel heat stimulation protocol was used in which 13 females with tension-type headache/TMD and 20 female controls were exposed to 11 painful heat stimuli at a rate of 0.33 Hz. Two temperature ranges (low, 44°C to 46°C; high, 45°C to 47°C) were tested on the cheek and arm in separate trials. Perceived pain was rated on a 100-mm visual analog scale after the second, sixth, and eleventh stimulus presentation and every 15 seconds after the final stimulus presentation (aftersensations) for up to 3 minutes. The duration of aftersensations was compared using the student unpaired t test with Welch correction. RESULTS: Temporal summation was not observed in any of the groups, but aftersensations were consistently reported. The aftersensations lasted longer in tension-type headache/TMD patients (right cheek, 100.4 ± 62.0 seconds; right arm, 115.4 ± 64.0 seconds) than in controls (right cheek, 19.5 ± 2.5 seconds; right arm, 20.3 ± 2.7 seconds) (P < .05). A cutoff value (right cheek, 44.6 seconds; right arm, 41.5 seconds) provided a sensitivity and specificity of 0.77 and 0.95, respectively, with the high stimulus protocol. CONCLUSION: The results from this pilot study suggest that aftersensations to painful heat stimulation can appear without temporal summation. Furthermore, the developed test protocol has a good predictive value and may have the potential to discriminate between tension-type headache/TMD patients and control subjects.

Intramuscular temperature modulates glutamate-evoked masseter muscle pain intensity in humans.

AIMS: To determine whether glutamate-evoked jaw muscle pain is altered by the temperature of the solution injected. METHODS: Sixteen healthy volunteers participated and received injections of hot (48°C), neutral (36°C), or cold (3°C) solutions (0.5 mL) of glutamate or isotonic saline into the masseter muscle. Pain intensity was assessed with an electronic visual analog scale (eVAS). Numeric rating scale (NRS) scores of unpleasantness and temperature perception, pain-drawing areas, and pressure pain thresholds (PPTs) were also measured. Participants filled out the McGill Pain Questionnaire (MPQ). Two-way or three-way repeated measures ANOVA were used for data analyses. RESULTS: Injection of hot glutamate and cold glutamate solutions significantly increased and decreased, respectively, the peak pain intensity compared with injection of neutral glutamate solution. The duration of glutamate-evoked pain was significantly longer when hot glutamate was injected than when cold glutamate was injected. No significant effect of temperature on pain intensity was observed when isotonic saline was injected. No effect of solution temperature was detected on unpleasantness, heat perception, cold perception, area of pain drawings, or PPTs. There was a significantly greater use of the "numb" term in the MPQ to describe the injection of cold solutions compared to the injection of both neutral and hot solutions. CONCLUSION: Glutamate-evoked jaw muscle pain was significantly altered by the temperature of the injection solution. Although temperature perception in the jaw muscle is poor, pain intensity is increased when the muscle tissue temperature is elevated.