Circulating Lipids and Acute Pain Sensitization: An Exploratory Analysis.

BACKGROUND: In individuals with low back pain, higher lipid levels have been documented and were associated with increased risk for chronic low back pain. OBJECTIVES: The purpose of this research was to identify plasma lipids that discriminate participants with acute low back pain with or without pain sensitization as measured by quantitative sensory testing. METHODS: This exploratory study was conducted as part of a larger parent randomized controlled trial. A cluster analysis of 30 participants with acute low back pain revealed two clusters: one with signs of peripheral and central sensitivity to mechanical and thermal stimuli and the other with an absence of peripheral and central sensitivity. Lipid levels were extracted from plasma and measured using mass spectroscopy. RESULTS: Triacylglycerol 50:2 was significantly higher in participants with peripheral and central sensitization compared to the nonsensitized cluster. The nonsensitized cluster had significantly higher levels of phosphoglyceride 34:2, plasmenyl phosphocholine 38:1, and phosphatidic acid 28:1 compared to participants with peripheral and central sensitization. Linear discriminant function analysis was conducted using the four statistically significant lipids to test their predictive power to classify those in the sensitization and no-sensitization clusters; the four lipids accurately predicted cluster classification 58% of the time (R = .58, -2 log likelihood = 14.59). DISCUSSION: The results of this exploratory study suggest a unique lipidomic signature in plasma of patients with acute low back pain based on the presence or absence of pain sensitization. Future work to replicate these preliminary findings is underway.

Comparison of Low Back Pain Recovery and Persistence: A Descriptive Study of Characteristics at Pain Onset.

BACKGROUND: Persistent low back pain is a significant problem worldwide. Early identification and treatment of individuals at high risk for persistent low back pain have been suggested as strategies to decrease the rate of disability associated with this condition. PURPOSE: To examine and compare demographic, pain-related, psychological, and somatosensory characteristics in a cohort of participants with acute low back pain who later went on to experience persistent low back pain or whose pain resolved within the first 6 weeks after initial onset. METHODS: A descriptive study was conducted among men and women 18-50 years of age who had an acute episode of low back pain. Study questionnaires were administered to collect demographic information and measures of pain, coping, reactivity, mood, work history and satisfaction, and disability. A standardized protocol of quantitative sensory testing was performed on each participant at the painful area of their low back and at a remote site on their arm. RESULTS: The sample consisted of 48 participants, of whom 19 went on to develop persistent low back pain and 29 resolved. Compared to the resolved group, the persistent low back pain group was significantly older and had a lower level of educational attainment, a higher body mass index, and higher mean "least" pain score on the Brief Pain Inventory-Short Form. Significantly higher thermal detection thresholds at the painful and remote sites as well as signs of central sensitivity differentiated the persistent pain group from the resolved group during the acute stage of low back pain.

Methods to measure peripheral and central sensitization using quantitative sensory testing: A focus on individuals with low back pain.

Quantitative sensory testing can be used to assess peripheral and central sensitization; important factors that contribute to the individual's experience of pain and disability. Many studies use quantitative sensory testing in patients with low back pain to detect alterations in pain sensitivity, however, because investigators employ different protocols, interpretation of findings across studies can become problematic. The purpose of this article is to propose a standardized method of testing peripheral and central pain sensitization in patients with low back pain. Video clips are provided to demonstrate correct procedures for measuring the response to experimental pain using mechanical, thermal and pressure modalities. As nurse researchers and clinicians increase utilization of quantitative sensory testing to examine pain phenotypes, it is anticipated that more personalized methods for monitoring the trajectory of low back pain and response to treatment will improve outcomes for this patient population.

Acute Low Back Pain: Differential Somatosensory Function and Gene Expression Compared With Healthy No-Pain Controls.

OBJECTIVES: Low back pain (LBP) is the second most frequently diagnosed pain condition in the United States, and although a majority of individuals have resolution of pain during the acute period, an estimated 40% of individuals will experience persistent pain. Given the heterogenous nature of LBP, this study sought to describe and compare somatosensory and molecular (gene expression) profiles between individuals with acute LBP and healthy no-pain controls. METHODS: Using a previously established protocol, we comprehensively assessed somatosensory parameters among 31 no-pain control participants and 31 participants with acute LBP. Samples of whole blood were drawn to examine mRNA expression of candidate genes involved in the transduction, maintenance, and modulation of pain. RESULTS: The acute LBP group exhibited increased pain sensitivity to cold stimuli, mechanical stimuli, including mechanical temporal summation at both the painful back area and remote location suggesting a mechanism of enhanced central nervous system excitability. In addition, deep tissue-specific peripheral sensitization was suggested due to significant differences in pressure pain threshold of the painful back area, but not the remote body site. Several genes that were differentially expressed were significantly associated with somatosensory alterations identified in the acute LBP group. DISCUSSION: Acute LBP participants showed selective pain sensitivity enhancement and differential gene expression profiles compared with pain-free controls. Further research to characterize pain-associated somatosensory changes in the context of altered mRNA expression levels may provide insight on the molecular underpinnings of maladaptive chronic pain.

Mammalian mitochondrial and cytosolic folylpolyglutamate synthetase maintain the subcellular compartmentalization of folates.

Folylpoly-γ-glutamate synthetase (FPGS) catalyze the addition of multiple glutamates to tetrahydrofolate derivatives. Two mRNAs for the fpgs gene direct isoforms of FPGS to the cytosol and to mitochondria in mouse and human tissues. We sought to clarify the functions of these two compartmentalized isoforms. Stable cell lines were created that express cDNAs for the mitochondrial and cytosolic isoforms of human FPGS under control of a doxycycline-inducible promoter in the AUXB1 cell line. AUXB1 are devoid of endogenous FPGS activity due to a premature translational stop at codon 432 in the fpgs gene. Loss of folates was not measurable from these doxycycline-induced cells or from parental CHO cells over the course of three CHO cell generations. Likewise, there was no detectable transfer of folate polyglutamates either from the cytosol to mitochondria, or from mitochondria to the cytosol. The cell line expressing cytosolic FPGS required exogenous glycine but not thymidine or purine, whereas cells expressing the mitochondrial isoform required exogenous thymidine and purine but not glycine for optimal growth and survival. We concluded that mitochondrial FPGS is required because folate polyglutamates are not substrates for transport across the mitochondrial membrane in either direction and that polyglutamation not only traps folates in the cytosol, but also in the mitochondrial matrix.