Retrospective Study of the Safety and Efficacy of Intraoperative Methadone for Pain Management in Patients Undergoing Elective Intracranial Surgery.

BACKGROUND: Patients undergoing intracranial surgery experience significant perioperative pain and are typically treated with short-acting opioids. Methadone, with its prolonged half-life and multimodal central nervous system effects, presents a promising option for managing postcraniotomy pain. Despite its proven efficacy in other types of surgeries, the use of methadone in patients undergoing craniotomy has not yet been explored. METHODS: A retrospective chart review was conducted for 60 adult patients ranging in age from 18 to 81 years who received methadone during intracranial surgeries. The primary outcome of interest was the total opioid consumption in oral morphine milligram equivalents (MMEs) and patient-reported pain scores within 24 hours and up to 72 hours postoperatively. RESULTS: The methadone dosage varied from 5 to 20 mg. In the infratentorial group, the median total MME on postoperative day 1, 2, and 3 was 30.5, 17, and 0.8, respectively, with mean pain scores of 3.56, 3.91, and 2.71. In the supratentorial group, the median total MME on postoperative day 1, 2, and 3 was 17.85, 15.4, and 1.2, with mean pain scores of 2.31, 1.68, and 2.21, respectively. Patients who were chronic opioid users had significantly higher pain scores and average opioid use (P < 0.05). None of the patients required administration of naloxone or airway interventions. Comparison with the historical control showed that our study patients had lower pain scores and MME. CONCLUSIONS: The single intraoperative dose of methadone is well tolerated by adult patients undergoing various types of intracranial surgeries, with minimal side effects, including elderly patients aged 65 years or older.

Promoter polymorphisms in the MATP (SLC45A2) gene are associated with normal human skin color variation.

Human pigmentation is a complex physical trait in which the membrane-associated transporter protein (MATP) plays an important role as it is involved in intracellular processing and trafficking of melanosomal proteins. Recently, pathogenic mutations in MATP have been shown to cause oculocutaneous albinism type 4, while other polymorphisms are known to have a role in normal pigmentation variation. We previously reported significant associations of two coding region polymorphisms with hair, skin, and eye color in Caucasians. Here we characterize the promoter region of MATP identifying two new transcription start sites and a novel duplication (c.-1176_-1174dupAAT). A total of 700 individuals from five different population groups (529 Caucasians, 38 Asians, 46 African Americans, 47 Australian Aborigines, and 40 Spanish Basques) were genotyped for known promoter polymorphisms c.-1721C>G (rs13289) and c.-1169G>A (rs6867641), as well as c.-1176_-1174dupAAT. Allele frequencies of all three polymorphisms were significantly different between population groups. In Caucasians, the -1721G, +dup, and -1169A alleles were significantly associated with olive skin color. The three promoter polymorphisms were found to be in linkage disequilibrium with each other but not with the two previously reported coding region polymorphisms. Functional analyses in a melanoma cell line showed that the promoter haplotype -1721G, +dup, -1169A significantly decreased MATP transcription. This report provides further evidence for the involvement of MATP in normal pigmentation variation by identifying associations between MATP alleles and skin color variation in Caucasians and demonstrating a functional significance of these polymorphisms.

Single nucleotide polymorphisms in the MATP gene are associated with normal human pigmentation variation.

Human physical pigmentation is determined by the type and amount of melanin and the process of pigmentation production probably involves more than 100 genes. A failure to synthesize melanin results in oculocutaneous albinism (OCA). A recently identified form of OCA results from mutations in the Membrane Associated Transporter Protein (MATP) gene. The role of MATP in human pigmentation is not clear. We investigated the role of two nonpathogenic nonsynonymous single nucleotide polymorphisms (SNPs) in the MATP gene to determine if they are associated with normal human skin, hair, and eye color variation. A total of 608 individuals from four different population groups (456 Caucasians, 31 Asians, 70 African-Americans, and 51 Australian Aborigines) were genotyped for c.814G>A (p.Glu272Lys) and c.1122C>G (p.Phe374Leu). Results indicate that the allele frequencies of both polymorphisms are significantly different between population groups. The two alleles, 374Leu and 272Lys, are significantly associated with dark hair, skin, and eye color in Caucasians. The odds ratios (ORs) of the LeuLeu genotype for black hair and olive skin are 25.63 and 28.65, respectively, and for the LysLys genotype are 43.23 and 8.27, respectively. The OR for eye color is lower at 3.48 for the LeuLeu and 6.57 for LysLys genotypes. This is the first report of this highly significant association of MATP polymorphisms with normal human pigmentation variation.