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The Pain Protective Haplotype: Introducing the Modern Genetic Test

Yale University School of Medicine, Department of Genetics, 333 Cedar St., New Haven, CT 06510, Fax 216-896-0568, E-mail roger.klein@yale.edu

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Chronic pain is a major health problem, affecting 2%–46.5% of adult populations (1)(2). In the United States, common pain conditions account for approximately $61.2 billion in lost workplace time (3). The human sensation of pain is affected by an individual’s past experiences, health status, psychological state, cultural and ethnic backgrounds, pain-coping skills, age, sex, and even pending litigation (4)(5). Emotional variables profoundly influence the perception of painful stimuli (6). In addition, genetic contributions to the experience of pain have increasingly been recognized (7). However, the complexity of pain processing, the multiplicity of influences on it, and the sensation’s inherent subjectivity and protean manifestations make the elucidation of relevant heritable factors extremely challenging.

Neuropathic pain is caused by injury to, or dysfunction of, the peripheral or central nervous system (8). It is particularly troublesome because of its prevalence, severity, chronicity, and resistance to therapy (9). Patients with conditions as diverse as diabetes mellitus, alcoholism, HIV, multiple sclerosis, postherpetic neuralgia, and spinal radiculopathies may suffer from chronic neuropathic pain. Radiculopathic pain is among the most frequently encountered neuropathic pain syndromes (8)(9).

Sciatica associated with intervertebral disc herniation is the most common type of radicular leg pain in adult working populations (10). Although many patients with herniated discs have favorable outcomes with medical therapy, individuals who have ongoing or severe pain often undergo lumbar discectomy. Recently, Tegeder et al. (11) described a putative association between an apparently common haplotype (15.4% of alleles in the study population) of the GTP cyclohydrolase gene (dopa-responsive dystonia, GCH1) and lower degrees of persistent pain after back surgery.

GTP cyclohydrolase is the rate-limiting enzyme in tetrahydrobiopterin (BH4) synthesis. BH4 serves as . . . [Full Text of this Article]

The following articles in journals at HighWire Press have cited this article:

				R. D. Klein and M. J. Mahoney LabCorp v. Metabolite Laboratories: The Supreme Court Listens, but Declines to Speak. J. Law Med. Ethics, March 1, 2008; 36(1): 141 - 149. [PDF]