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Background and objective Chronic low back pain (CLBP) is highly prevalent, with a substantial psychosocial burden. Pain has both sensory and affective components. The latter component is a significant driver of disability and psychiatric comorbidity but is often inadequately treated. Previously we reported that noninvasive transcranial direct current stimulation (tDCS) may modulate pain-associated affective distress. Here we tested whether 10 daily tDCS sessions aimed to inhibit the left dorsal anterior cingulate cortex (dACC), a region strongly implicated in the affective component of pain, would produce selective reduction in pain-related symptoms. Methods In this multisite, double-blinded, randomized placebo-controlled trial (RCT), 21 CLBP patients received 10 weekday sessions of 2-mA active tDCS or sham (20 minutes/session). A cathodal electrode was placed over FC1 (10-20 electroencephalography coordinates), and an identical anodal return electrode was placed over the contralateral mastoid. Participants rated pain intensity, acceptance, interference, disability, and anxiety, plus general anxiety and depression. Results Regression analysis noted significantly less pain interference (P =0.002), pain disability (P =0.001), and depression symptoms (P =0.003) at six-week follow-up for active tDCS vs sham. Omnibus tests suggested that these improvements were not merely due to baseline (day 1) group differences. Conclusions To our knowledge, this is the first double-blinded RCT of multiple tDCS sessions targeting the left dACC to modulate CLBP's affective symptoms. Results are encouraging, including several possible tDCS-associated improvements. Better-powered RCTs are needed to confirm these effects. Future studies should also consider different stimulation schedules, additional cortical targets, high-density multi-electrode tDCS arrays, and multimodal approaches.

Background and Objectives. Ropivacaine is a long-acting local anesthetic similar to bupivacaine, but with lower cardiac toxicity and intrinsic vasoconstrictive properties that may reduce the risk and extent of systemic plasma absorption. Plasma levels and risks are associated with the total dose used and the extent of absorption, with lower doses potentially representing less risk. Although both 0.5% and 0.75% ropivacaine provide adequate analgesia for wound infiltration after hernia repair, the efficacy of lower doses and the early systemic absorption have not been reported. Methods. We studied postoperative pain and systemic plasma levels following either the injection of 30 mL of saline or 0.125%, 0.25%, or 0.5% ropivacaine into the wounds in 110 healthy patients following hernia repair under spinal anesthesia. Pain was assessed using visual analog scale (VAS) scores and algometer readings at rest and after coughing, and oral analgesic requirements were assessed in the first 5 hours after surgery and for the week after discharge. Results. Both 0.25% and 0.5% ropivacaine provided pain relief following surgery when compared with saline or 0.125%. No adverse reactions to the drug were reported in any group. Plasma levels of ropivacaine peaked between 30 and 60 minutes, at 0.109, 0.249, and 0.399 mg/L for 0.125%, 0.25%, and 0.5% concentrations, respectively. Although the levels were below those producing clinical symptoms, they remained elevated for the entire 2-hour sampling period. This implies an absorption-dependent elimination which is substantially longer than reported with other routes of injection. Conclusions. Ropivacaine 0.25% and 0.5% is adequate for pain relief after outpatient hernia repair, whereas the 0.125% solution is no more effective than saline. Prolonged systemic absorption from peripheral injection may be associated with prolonged elevations of plasma concentrations, which potentially could be associated with unexpectedly high plasma levels if repeated injections are performed in the perioperative period with higher concentrations or doses.

Prescription opioid-acetaminophen products account for the majority of cases of acetaminophen-related acute liver failure in the United States. We sought to examine the frequency of opioid-acetaminophen overuse at the Providence VA Medical Center and improve the quality and safety of opioid-acetaminophen prescription practices in a system employing electronic health records and e-prescribing.During fiscal year 2011, the Providence VA pharmacy dispensed a total of 19,841 acetaminophen prescriptions to a total of 4455 different patients. There were only 15 acetaminophen prescriptions dispensed in excess of 4g/day, and there were only 14 patients exposed to a potential maximum daily dose of acetaminophen greater than 4g.The Providence VAMC appears to have a low rate of prescription acetaminophen misuse, in contrast to rates seen in previous studies. The VHA electronic health record, accessible to all healthcare providers, appears to offer considerable benefit in reducing the overuse of acetaminophen containing opioid products.

It is unfortunate that well-meaning individuals can often find themselves at odds over issues where both parties share similar goals, that of improving the health and well-being of the populace, due to differing perspectives of the same issue. As health care providers focused on reducing suffering and improving comfort, physicians are eager to provide pain relief, often in the form of opioid analgesics. Over the recent decade, we have witnessed a greater emphasis on the diagnosis and treatment of pain. Although many of us still see considerable room for improvement in the quality of pain treatment in the United States, in fact, substantial gains have been made. Pain assessment has become an accepted standard in the care of hospitalized patients, and there is a greater expectation on the part of our patients for pain relief. One hallmark of this success has been the development of federally funded guidelines for the management of cancer and acute perioperative pain. Another indicator has been the dramatic escalation in the use of opioid analgesics. Based on data from the U.S. Drug Enforcement Agency (DEA) Automation of Reports and Consolidated Order System (ARCOS), which monitors opioid production and delivery to retail pharmacies, between 1997 and 2004 the amount of oxycodone, hydrocodone, and methadone delivered increased by 640%, 275%, and 903%, respectively. From the perspective …

The past 20 years have seen a great surge of interest in understanding and treating pain. The introduction of sustained-release opioid delivery systems has tremendously advanced our ability to provide improved pain control. Parenteral opioid delivery systems, although available in many developed nations, remain expensive and cumbersome. New advances in parenteral sustained-release systems are currently in development. These advances include liposomal opioid preparations for intrathecal use, transcutaneous patient-controlled delivery, and implantable diffusion reservoirs. Even more exciting are new developments in tissue engineering that may allow the transplantation of human or animal cells, capable of producing natural analgesic substances, into the vicinity of the spinal cord.

In 2001, the Joint Commission for Accreditation of Healthcare Organizations (JCAHO) introduced a series of compliance guidelines designed to improve pain care. JCAHO acknowledged that freedom from pain is a patient right, and proposed specific requirements to improve pain assessment, and to monitor treatment. A major requirement for conformity to these guidelines was the need for health care institutions to establish a monitoring system to assess pain at appropriate intervals, and to document the effectiveness of treatment. To adhere to the guidelines, most health care organizations have adopted the use of one or more pain scales to be included along with the standard patient vital signs, hence, the concept of pain as the 5th vital sign. Like most pain specialists, I welcomed the much needed attention being directed at improving the recognition and treatment of our patient's pain. In the perioperative pain patient, this effort has proven advantageous by insuring that pain complaints will be taken more seriously, and has resulted in standards that require a patient's pain be controlled prior to discharge from the postanesthesia care unit, as documented by specific pain scale values. Unfortunately, the value of pain scales may vary considerably in their meaning and value in different patients, and in different care settings. For example, in the postanesthesia care unit, a location where pain may …

The creation of an institutional identity is an essential process in the development of a successful product, business, or organization. Efforts to link a product or service to a specific brand name identity can be critical in obtaining consumer acceptance, and is often easier said than done. When successful, a brand name becomes synonymous with the organization, process, or product formulating a unique public awareness. Classic examples include Xerox, Heimlich maneuver, and the AMA. Although not specifically descriptive to the process or product, the names call to mind clear images and meaning. As an organization, the American Academy of Pain Medicine (AAPM) has struggled to create a unique identity for pain medicine. The AAPM was originally founded as the American Academy of Algology. The origins of the name derive from algos, the Greek word for pain. Derivations of this word include algesia, a commonly used …

In the relative scheme of organized medicine, the American Academy of Pain Medicine (AAPM) remains but a small voice surrounded by the many primary care and specialty medical societies competing to be heard on the national scene. Certainly, there is a strong legitimacy to our message, as there is to the message of each and every special interest group; unfortunately, with the escalating competition from so many of medicine's “voices,” being heard in the crowd is becoming increasingly difficult. It does not take an actuary to recognize that we are rapidly approaching a point at which health care expenditure cannot be sustained. The threat of cuts in physician payment has loomed over the already meager Medicare reimbursement for the past several years. Employers are increasingly limiting both pension and health care funding, potentially leaving many patients facing the possibility of going without health care coverage. Significant change must take place in the U.S. health care system, and it is essential that we, as pain physicians, become authors of this change to ensure that our patients continue to have access to effective and appropriate pain treatment. In this environment of escalating competition for health care dollars, there are no guarantees that the proper decision-making process will occur, unless we assume an active role in guiding and implementing that process with our ultimate goal being the best pain care for our …

The recent completion of the 22nd annual meeting of the American Academy of Pain Medicine (AAPM) marked another successful landmark in the evolution of the Academy. Special thanks are owed to our conference chair, Todd Sitzman, and to his cochairs, Gagan Mahajan, Bill McCarberg, Jerome Schofferman, Donna Bloodworth, and all of the program committee members responsible for organizing this year's outstanding conference. I would also like to congratulate our outgoing president, Scott Fishman, for his efforts over the past year. Scott was directly responsible for influencing media attention to the plight of patients afflicted with painful conditions, and to engender greater public awareness of the role pain medicine specialists play in the diagnosis and treatment of pain. His efforts have highlighted the role of the AAPM in promoting pain education for physicians and in creating a greater social awareness of pain and the need for proper treatment. It was a banner year for the Academy. I would also like to acknowledge the accomplishments of several outgoing members of the Board of Directors. Dan Carr has served in many capacities within the …

Who is the Patient's Best Advocate? During the preliminary stages of our medical careers, we are imbued with the collected knowledge of scientists, clinicians, and philosophers. These facts, principles, and pathways provide the basis upon which our clinical careers in medicine are founded. Despite the considerable knowledge accumulated, our ability to predict the course of a disease, in any given individual, remains an educated guess. Unfortunately, our patients and society require more of us. Due to the economic impact of lost productivity and health care expenditures on business interests, and the loss of personal income for the patient, physicians are expected to foster a recommendation regarding the victim's injuries. Lost function, inability to return to …

Human peripheral lymphocytes incubated with 2'-deoxycoformycin and 2'-deoxyadenosine (dAdo) reached a plateau in dATP accumulation after 4 hr that lasted for up to 24 hr. Total dATP accumulation did not exceed 15% of the control ATP concentration in the lymphocytes. In contrast, the human CCRF-CEM T lymphoblastic cell line and human erythrocytes showed a nearly linear pattern of dATP formation throughout the incubation period. By 6 hr the dATP concentration in the CCRF-CEM cells exceeded the control ATP concentration. A comparison of dATP accumulation in purified peripheral T and B lymphocytes indicated differences between these cells that favor greater dATP formation in the B lymphocytes. Incorporation studies with several adenosine analogs demonstrated that arabinosyladenine, 2-F-arabinosyladenine, tubercidin, formycin A, and 9-(2'-deoxy-2'-fluoro-beta-D-ribofuranosyl)adenine form corresponding amounts of analog triphosphate in the T and B cell-enriched lymphocytes. 9-(2'-Deoxy-2'-fluoro-beta-D-arabinofuranosyl)adenine (2'-F-araA) was the only compound to show an incorporation pattern similar to that observed with dAdo by forming analog triphosphate only in the B cell-enriched lymphocyte population. Nucleoside kinase measurements showed no significant differences in dAdo, adenosine, or 2'-deoxycytidine kinase activities between the T and B lymphocytes. The inability of the T cells to incorporate dAdo or the analog 2'-F-araA into their nucleotide pools may indicate the existence of a highly specific catabolic enzyme(s).

Several B lymphoblastic cell lines are known to be relatively resistant to the combination of 2'-deoxyadenosine with an adenosine deaminase inhibitor. These cell lines are believed to have a greater capacity to dephosphorylate 2'-deoxyadenosine nucleotides, thus preventing excessive accumulation of potentially toxic metabolites. In this study, the 2'-deoxynucleoside 5'-monophosphate dephosphorylating activities of human peripheral lymphocytes were examined. Peripheral lymphocytes have at least three nucleotide 5'-monophosphate nucleotidases distinguished by different pH optimums, substrate preference, Mg2+ requirement, inhibitors, and molecular weights. Two of the enzymes appeared to be cytosolic, only one of which had significant substrate activity with dAMP. This enzyme had an acidic pH optimum (5.0), no Mg2+ requirement, was inhibited by tartrate, and demonstrated broad substrate specificity. The other cytosolic nucleotidase required Mg2+, had a pH optimum of 5.5 to 6.0, was activated by 2'-deoxyinosine, and demonstrated a substrate preference for 3'- and 5'-monophosphate 2'-deoxynucleosides of hypoxanthine, guanine, uracil, and thymine. The third enzyme, ecto 5'-nucleotidase, is associated with the cell membrane. Although the ecto 5'-nucleotidase activity was higher in the B lymphocytes, the cytosolic nucleotidases were similar in activity in the T and B lymphocytes.

The effects of the chiral isomers of erythro - and threo -9-(2-hydroxy-3-nonyl)adenines (EHNA and THNA) on purine metabolism in Sarcoma 180 cells have been determined. At concentrations of 10–80 μM [10- to 1000-fold greater than their K i values with adenosine deaminase (ADA)], all isomers inhibited purine salvage and biosynthesis de novo . Although (+)-EHNA, the most potent ADA inhibitor, exerted the greatest effects, there was no direct correlation between the potency of ADA inhibition and the secondary effects on purine metabolism, e.g. (+)-EHNA is about 2-fold more inhibitory than (−)-EHNA in blocking purine base incorporation but about 250-fold more potent as an inhibitor of ADA ( K i of (+)-EHNA = 500nM[Bessodes et al., Biochem. Pharmac. 31 , 879 (1982)]). All the isomers inhibited the incorporation of radiolabeled purine bases (adenine, guanine and hypoxanthine) and nucleosides (guanosine and inosine) into acid-soluble nucleotides and of glycine into 5′-phosphoribosyl-formylglycineamide. Unlike the results of Henderson et al. [ Biochem. Pharmac. 26 , 1967 (1977)] with Ehrlich ascites cells, the incorporation of adenosine into nucleotides was only slightly inhibited in Sarcoma 180 cells. (+)-EHNA did not inhibit the activities of 5-phosphoribosyl-1-pyrophosphate (PRPP) synthetase, purine phosphoribosyltransferases or nucleotide kinases in cell extracts. Accumulation of PRPP was inhibited only under conditions that fostered rapid synthesis.