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Catechol-O-methyltransferase genotype predicts pain severity in hospitalized burn patients.

ABSTRACT: Increasing evidence suggests that stress system activation after burn injury may contribute to burn-related pain. If this is the case, then genetic variations influencing the function of important stress system components, such as the enzyme catechol-O-methyltransferase (COMT), may predict pain severity after thermal burn injury. The authors evaluated the association between COMT genotype and pain intensity in 57 individuals hospitalized after thermal burn injury. Consenting participants at four burn centers were genotyped and completed daily 0 to 10 numeric rating scale pain assessments on 2 consecutive days including evaluation of waking, least, and worst pain. The association between COMT genotype and individual pain outcomes was calculated using a linear mixed model adjusting for sociodemographic and burn injury characteristics. Overall pain (combination of least, worst, and waking pain scores) was significantly higher in patients with a COMT pain vulnerable genotype (6.3 [0.4] vs 5.4 [0.4], P = .037). Individuals with a COMT pain vulnerable genotype also had significantly higher "least pain" scores (3.8 [0.5] vs 2.6 [0.4], P = .017) and significantly higher pain on awakening (6.8 [0.5] vs 5.3 [0.4], P = .004). Differences in worst pain according to genotype group were not significant. COMT pain vulnerable genotype was a stronger predictor of overall pain severity than burn size, burn depth, or time from admission to pain interview assessment. These findings suggest that genetic factors influencing stress system function may have an important influence on pain severity after burn injury. Further studies of genetic predictors of pain after burn injury are needed.

SUBMITTER: Orrey DC

PROVIDER: S-EPMC3319634 | biostudies-literature | 2012 Jul-Aug

REPOSITORIES: biostudies-literature

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Catechol-O-methyltransferase genotype predicts pain severity in hospitalized burn patients.

Orrey Danielle C DC Bortsov Andrey V AV Hoskins Janelle M JM Shupp Jeffrey W JW Jones Samuel W SW Cicuto Bryan J BJ Hwang James J Jordan Marion H MH Holmes James H JH Haith Linwood R LR Roane Brandon M BM Diatchenko Luda L Cairns Bruce A BA McLean Samuel A SA

Journal of burn care & research : official publication of the American Burn Association 20120701 4

Increasing evidence suggests that stress system activation after burn injury may contribute to burn-related pain. If this is the case, then genetic variations influencing the function of important stress system components, such as the enzyme catechol-O-methyltransferase (COMT), may predict pain severity after thermal burn injury. The authors evaluated the association between COMT genotype and pain intensity in 57 individuals hospitalized after thermal burn injury. Consenting participants at four ...[more]

PMID: 22210062

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Project description:BACKGROUND:Patients with chronic pain disorders exhibit increased levels of catecholamines alongside diminished activity of catechol-O-methyltransferase (COMT), an enzyme that metabolizes catecholamines. The authors found that acute pharmacologic inhibition of COMT in rodents produces hypersensitivity to mechanical and thermal stimuli via ?-adrenergic receptor (?AR) activation. The contribution of distinct ?AR populations to the development of persistent pain linked to abnormalities in catecholamine signaling requires further investigation. METHODS:Here, the authors sought to determine the contribution of peripheral, spinal, and supraspinal ?ARs to persistent COMT-dependent pain. They implanted osmotic pumps to deliver the COMT inhibitor OR486 (Tocris, USA) for 2 weeks. Behavioral responses to mechanical and thermal stimuli were evaluated before and every other day after pump implantation. The site of action was evaluated in adrenalectomized rats receiving sustained OR486 or in intact rats receiving sustained ?AR antagonists peripherally, spinally, or supraspinally alongside OR486. RESULTS:The authors found that male (N = 6) and female (N = 6) rats receiving sustained OR486 exhibited decreased paw withdrawal thresholds (control 5.74 ± 0.24 vs. OR486 1.54 ± 0.08, mean ± SEM) and increased paw withdrawal frequency to mechanical stimuli (control 4.80 ± 0.22 vs. OR486 8.10 ± 0.13) and decreased paw withdrawal latency to thermal heat (control 9.69 ± 0.23 vs. OR486 5.91 ± 0.11). In contrast, adrenalectomized rats (N = 12) failed to develop OR486-induced hypersensitivity. Furthermore, peripheral (N = 9), but not spinal (N = 4) or supraspinal (N = 4), administration of the nonselective ?AR antagonist propranolol, the ?2AR antagonist ICI-118,511, or the ?3AR antagonist SR59230A blocked the development of OR486-induced hypersensitivity. CONCLUSIONS:Peripheral adrenergic input is necessary for the development of persistent COMT-dependent pain, and peripherally-acting ?AR antagonists may benefit chronic pain patients.

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Catechol-O-methyltransferase genotype predicts pain severity in hospitalized burn patients.

Publications

Catechol-O-methyltransferase genotype predicts pain severity in hospitalized burn patients.

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