Publications

Pulmonary emphysema results from the loss of intricate alveolar architecture and progressive simplification of small and highly effective gas-exchanging units into large, inefficient cyst-like spaces. Because of the loss of alveolar gas-exchanging units and the capillary bed within them, blood oxygen levels eventually fall and pressures within the pulmonary circulation rise. Recent insights from genetically manipulated mouse models have refined our understanding of the molecular events that prevent or promote the development of pulmonary emphysema. Capitalizing on an improved molecular understanding of emphysema with improved therapeutics has the potential to enhance both the survival and quality of life of patients with this common lung disease.

For patients with acute lung injury, positive pressure mechanical ventilation is life saving. However, considerable experimental and clinical data have demonstrated that how clinicians set the tidal volume, positive end-expiratory pressure, and plateau airway pressure influences lung injury severity and patient outcomes including mortality. In order to better identify ventilator-associated lung injury (VALI), clinical investigators have sought to measure blood-borne and airspace biological markers of VALI. At the same time, several laboratory-based studies have focused on biological markers of inflammation and organ injury in experimental models in order to clarify the mechanisms of ventilator-induced lung injury (VILI) and VALI. This review summarizes data on biological markers of VALI and VILI from both clinical and experimental studies with an emphasis on markers identified in patients and in the experimental setting. This analysis suggests that measurement of some of these biological markers may be of value in diagnosing VALI and in understanding its pathogenesis.

UNLABELLED

Although mechanical hyperalgesia associated with medical procedures is the major source of severe pain in burn-injured patients, little is known about its underlying mechanism. One reason for this has been the lack of a model for mechanical hyperalgesia at the site of injury. We have modified an established partial-thickness burn model in the rat to produce long-lasting primary mechanical hyperalgesia, which is present from the first measurement at 0.5 h, reaches a maximum at 3 days, and is still significant after 7 days. Because nerve growth factor (NGF), which is elevated in burn-injured tissue, produces mechanical hyperalgesia and activates protein kinase C (PKC)-epsilon, a key mediator in inflammatory and neuropathic pain, we used this model to evaluate the role of the NGF receptor, tyrosine-receptor kinase A (TrkA), and PKC-epsilon in burn-induced primary mechanical hyperalgesia. Intrathecal administration of antisense oligodeoxynucleotides to TrkA and PKC-epsilon, starting 3 days before inducing a burn injury, caused dose-related decrease of burn-induced primary mechanical hyperalgesia. In addition, intradermal injection of a PKC-epsilon-selective inhibitor eliminated hyperalgesia. Our model provides a method to elucidate the underlying mechanism of burn-injury pain as well as to screen for targets for novel analgesic treatments of this important clinical condition.

PERSPECTIVE

This manuscript presents the first model of thermal injury-induced mechanical hyperalgesia which mimics prolonged duration of clinical burn injury pain. We also perform proof of concept experiments demonstrating that our model provides a method to elucidate the mechanism of this important clinical condition.

BACKGROUND

Pain is a common symptom and significant problem for older adults; up to one half of community-dwelling older adults have pain that interferes with normal function.

OBJECTIVE

The goal of this study was to investigate the prevalence of pain among a racially and gender-balanced sample of community-dwelling older adults and evaluate sociodemographic factors associated with the reporting of pain. Both nonprescription (over-the-counter [OTC]) and prescription pain medications used by the participants and the sociodemographic factors associated with having medication prescribed were considered.

METHOD

This was a population-based, prospective, observational study. Subjects were participants in the University of Alabama at Birmingham (UAB) Study of Aging, a stratified random sample of Medicare beneficiaries who completed in-home interviews (1999-2001). Assessments included sociodemographic factors and pain; interviewers listed all prescription and OTC pain medications used. Pain medications were coded as NSAIDs, opiates, and miscellaneous pain medications. A composite ordinal measure reflecting pain severity and frequency ranged from 0 = no pain to 4 = dreadful or agonizing pain > or =4 times per week.

RESULTS

There were 1000 participants in the UAB Study of Aging (mean [SD] age, 75.3 [6.7] years; 50% black; 50% male; 51% rural residence). Seventy-four percent of the subjects reported pain; among these, 52% had daily pain, with 26% reporting dreadful or agonizing pain. Logistic regression controlling for other sociodemographic factors (age, gender, race, education, income, and marital status) found that rural residence (odds ratio [OR], 1.42; 95% CI, 1.1-1.9; P = 0.02) was significantly associated with the reporting of pain. Prescription pain medications were used by 35% of persons with pain and by 17% without pain (P < 0.001); OTC pain medications were used by 52% of persons with pain and by 45% of persons without pain (P = 0.06). Of persons reporting pain, 28% were taking neither prescription nor OTC pain medications; 16% took both and 20% took only prescription pain medications. Logistic regression found that factors associated with taking a prescription pain medication were: unmarried status (OR, 1.56; 95% CI, 1.1-2.2) and pain frequency/severity (OR, 1.39; 95% CI, 1.3-1.6). Taking an OTC pain medication was associated with lower odds of taking a prescription pain medication (OR, 0.50; 95% CI, 0.4-0.7). Age, gender, race, education, rural residence, transportation difficulty, income, and being on Medicaid were not associated with prescription pain medication use.

CONCLUSIONS

Prescription pain medication use was associated with pain frequency/severity after adjusting for sociodemographics and OTC pain medications in this study of community-dwelling older adults, suggesting that even with medications, individuals remained in pain.