Who Develops Persistent Disabling Low Back Pain?

The severity of pain itself at the onset of nonspecific low back pain does not reliably predict development of chronic back pain. According to new research, more important factors include general health status, functional impairment, and psychological factors such as maladaptive pain-coping behaviors and the presence of psychiatric comorbidities.

Writing in the April 7, 2010 edition of the Journal of the American Medical Association researchers noted that 85% of primary care patients with low back pain have conditions that are considered to be nonspecific, without evidence of serious underlying disorders (or “red flags”) such as cancer, infection, or anatomic defects [Chou and Shekelle 2010]. The question is, how can clinicians determine at early stages whether a patient with acute or subacute nonspecific low back pain will go on to develop a much worse, chronic back pain condition?

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Rheumatoid Arthritis Due to Vitamin D Deficiency?

Recent commentary and research have suggested a link between vitamin D deficiency and the development or worsening of rheumatoid arthritis (RA). However, more and better research is needed to reach more definitive conclusions.

In addition to its traditional functions affecting bone metabolism, vitamin D has been shown to modulate the immune system and its deficiency has been associated with the development of several autoimmune disorders, including RA. Similarly, other disorders recently mentioned as being induced or influenced by deficient vitamin D have included type 1 diabetes, multiple sclerosis, systemic lupus erythematosus, Behcet’s disease (chronic vasculitis), polymyositis-dermatomyositis, and systemic scleroderma [Pelajo et al. 2010].

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Acute Pain May Hijack the Limbic Brain

Pain and the Great Brain Robbery! Part 2

Various transformations have been found in the brains of persons with chronic pain, including abnormal chemistry, regional gray matter atrophy, cognitive changes, and unique patterns of brain activity. Now research suggests that acute pain episodes may alter the function of critical limbic brain regions to affect the development chronic back pain.

Researchers at Northwestern University, Chicago, imaged the brains of 16 healthy adults and 16 patients with chronic back pain using functional MRI (fMRI) while administering a series of different painful heat stimuli [Baliki et al. 2010]. During fMRI imaging, the brain activity while heat was being applied and the associated pain reported from it were similar between groups. However, healthy individuals showed significantly higher activity in a limbic-brain region called the nucleus accumbens [see illustration] as the thermal heat was decreasing and the pain was coming to an end (pain offset) compared with chronic pain patients (p<0.0001). This difference during offset of the pain distinguished the two groups with 100% sensitivity and 100% specificity, "implying that this signal can be used as an objective marker of chronic pain," the researchers reported in the April 15, 2010 issue of Neuron.

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Does Moderate Alcohol Drinking Benefit Arthritis?

Past research studies have suggested that moderate alcohol drinkers have a lower risk of developing rheumatoid arthritis (RA), and now new findings link such imbibing to a slower progression of the joint disease, particularly in men. However, this should not be viewed as an endorsement of alcohol consumption as either a preventative or remedial therapy.

According to a recent report by Reuters Health [Norton 2010], researchers in Switzerland found that light-to-moderate drinkers showed a slower progression of joint damage due to RA than nondrinkers. The findings, presented in the journal Arthritis & Rheumatism, were based on 2,908 Swiss adults who were part of a national database on RA patients [Nissen et al. 2010]. All had at least 2 sets of X-rays of their hands and feet over time, assessing erosions in 38 joints, and had been followed for an average of 4 years. Overall, 37% said they were nondrinkers at the outset, while the rest drank at least sometimes.

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High-Dose Aspirin Relieves Migraine Pain; Review

Aspirin 900 mg to 1,000 mg appears to provide significant pain relief within 2 hours for many persons suffering migraine headaches, according to a recent Cochrane review, and may offer advantages over other therapies. However, the potential hazards of this NSAID used too often and/or in higher doses need to be taken into account.

Updating an earlier Cochrane Systematic Review of the literature, researchers at the University of Oxford, UK, identified 13 good-quality clinical trials (n=4,222 participants) that compared aspirin 900 mg or 1,000 mg — alone or in combination with metoclopramide 10 mg (an antiemetic medication) — with placebo or other active comparators, mainly sumatriptan 50 mg or 100 mg [Kirthi et al. 2010]. All active treatments were superior to placebo and high-dose aspirin was found to be beneficial in providing short-term and sustained pain relief.

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Words Can Trigger Pain Centers in the Brain

Pain and the Great Brain Robbery! Part 1

New research shows that merely hearing pain-related words can fire-up the brain's pain centers. The clinical question is, when patients discuss, or just think about, their chronic physical pain symptoms can it actually make the pain worse?

Storage of painful experiences in memory is of biological advantage, since it encourages the avoidance of future situations that might cause physical pain and possibly be life threatening. Past research suggests that areas of the brain’s “pain matrix,” serving as a repository of painful memories, can be activated by environmental cues such as certain images or words. However, the particular areas of the brain affected and the specificity of verbal cues was unknown.

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Severe Chronic Pain is a Killer – Study Finds

Previous research has demonstrated a clearly negative influence of chronic pain on health. Now, a new study portrays a profound link between severe chronic pain and death; inflicting nearly a 70% greater mortality risk than even cardiovascular disease.

In 1996 a large cohort of 6,940 persons was recruited by researchers at the University of Aberdeen, UK, and information collected about chronic pain status, general health, and sociodemographic details [Torrance, et al. 2010]. Followup 10 years later linked these data with routinely collected national data for death registration. A total of 5,858 (84%) individuals from the original cohort were linked, including 1,557 (27%) who had died. The researchers found a significant association between chronic pain and all-cause mortality. Particularly troublesome was severe chronic pain — survival among persons with this condition was significantly worse than among those reporting mild or no chronic pain. Even after adjusting for various confounding sociodemographic factors and effects of long-term illness, patients with severe chronic pain had a 49% greater risk of death compared with all-cause mortality and a 68% greater risk of death compared with all cardiovascular-disease-related deaths.

COMMENT: The negative impact of severe chronic pain on survival discovered by this research is dramatic and concerning; especially when considering the recent brouhaha about purportedly high risks associated with analgesic agents, particularly opioids. In an objective risk-benefit analysis, it would appear from this study that the increased mortality risks associated with untreated or inadequately treated chronic pain could pose a greater threat than any hazards potentially associated with pain-relieving medication therapies. In brief — and this is admittedly a strong way of putting it — any restrictions on access to effective therapies for severe chronic pain might be tantamount to fostering premature death in the afflicted patients. *As always, reader comments are welcomed.*

REFERENCE: Torrance N, Elliott AM, Lee AJ, Smith BH. Severe chronic pain is associated with increased 10 year mortality. A cohort record linkage study. Eur J Pain. 2010(Apr);14(4):380-386 [abstract here].

U.S. FDA Approves New OxyContin Formulation

The U.S. Food and Drug Administration (FDA) just approved a new formulation of the popular controlled-release opioid pain reliever OxyContin®. The reformulated version is expected to help discourage misuse and abuse of the medication; although, caution is still needed by prescribers and patients.

Approved by the FDA in 1995 and manufactured by Purdue Pharma L.P., Stamford, CT, USA, the active ingredient in OxyContin is oxycodone, which slowly releases to treat patients who require around-the-clock medical management of moderate to severe pain with an opioid analgesic. Persons intent on abusing the previous formulation were able to release high levels of oxycodone all at once, contributing to high rates of abuse and potentially fatal overdose. There also were reports of inadvertent overdose with OxyContin after healthcare practitioners crushed the drug for administration to patients who could not swallow the tablet.

The reformulated version is intended to prevent immediate access to the full dose of oxycodone via cutting, chewing, or breaking the tablet. Furthermore, attempts to dissolve the tablets in liquid result in a gummy substance that cannot be drawn up into a syringe or injected. However, if administered in higher than recommended doses, the new formulation can still be abused or misused and result in overdose, so healthcare professionals need to remind their patients of the risks associated with using OxyContin not-as-directed. “Although this new formulation of OxyContin may provide only an incremental advantage over the current version of the drug, it is still a step in the right direction,” said Bob Rappaport, MD, of the FDA.

The FDA is requiring an “interim” REMS (Risk Evaluation and Mitigation Strategy) for this product that will include a Medication Guide for patients and required prescriber education regarding the appropriate use of opioid analgesics in the treatment of pain. Purdue also is required to conduct a postmarket study to collect data on the extent to which the new formulation reduces abuse and misuse of this opioid.

Sources:
> FDA Approves New Formulation for OxyContin [news release]. April 5, 2010 [available here].
> FDA teleconference; April 6, 2010. Presentation by Bob Rappaport, MD, and staff.
More Information:
> OxyContin - Questions and Answers. April 5, 2010 [available here].
> A Guide to Safe Use of Pain Medicine. February 23, 2009 [available here].

Consequences of Opioid-Induced Constipation

A large-scale investigation of patients starting long-term opioid analgesics demonstrated relatively low rates of therapy-induced constipation needing medical attention. However, such cases incurred significantly higher healthcare utilization costs, so strategies for minimizing this side effect of opioids are important.

Writing in the March 2010 edition of Managed Care, researchers described a study retrospectively examining medical claims data during a 7-year period from a large population of managed care enrollees to determine the impact of constipation in those who had started on long-term opioid analgesics. They identified 39,485 patients in this group, of whom 2,519 (6.4%) sought medical care for opioid-induced constipation within one year of starting therapy. Most were female (66%) and ≥45 years of age (68%). Outcomes were contrasted with a matched cohort of patients (controls) who did not have medical claims for constipation as a result of being prescribed long-term opioid therapy.

Compared with controls, the constipation group had significantly higher rates of concurrently taking ≥2 opioid analgesics and being switched or rotated between opioids. Patients with constipation claims also had significantly greater rates of physician office visits, other outpatient or ancillary care, emergency department visits, hospital admissions, home health services, nursing home care, and laboratory tests. Consequently, as a group, those with constipation incurred much higher healthcare costs as compared with patients without constipation.

COMMENTARY: The rate of opioid-induced constipation requiring medical attention in this study actually seems low (6.4%); however, it is not known if a great many more patients developed less severe constipation and either did not seek care or self-treated the condition with OTC remedies. Furthermore, it is interesting to note that 8% of patients in the control group, without constipation-related medical claims, had been prescribed laxatives, probably as preventive therapy to minimize constipation at the outset. Most opioid-therapy guidelines recommend immediately starting patients on a “bowel regimen,” often including prescribed laxatives, to minimize the risk or severity of constipation. Finally, it should be mentioned that the authors of this study were all associated with or funded by Pfizer Inc. (previously, Wyeth Research), a manufacturer of laxative products, which might have influenced a reporting bias.

REFERENCE: Iyer S, Davis KL, Candrilli S. Opioid use patterns and health care resource utilization in patients prescribed opioid therapy with and without constipation. Managed Care. 2010(Mar):44-51 [article here].
INFO for Your Patients: Constipation: A Common Side Effect of Opioid Use by Kevin Zacharoff, MD, at PainAction.com [available here].

Pediatricians Wary of Treating Chronic Pain

Many pediatricians do not consider it their responsibility to treat severe, chronic pain in their young patients, according to a new survey. Meanwhile, children’s pain is often undertreated, so the need for equitable and effective pain management services for this population is a vital concern.

Writing in the Journal of Palliative Medicine, researchers from the University of Florida College of Medicine reported on a survey addressing pediatric chronic pain and palliative care sent to a random sample of 800 U.S. pediatricians. Of the 303 responding, most were non-Hispanic white (56%), and had been in practice 10 or more years (68%). Only about one third of pediatricians (32%) felt it was their responsibility to treat chronic pain; most believed pain specialists (58%), other specialists (40%), and/or hospice providers (26%) should be responsible. Acetaminophen and nonsteroidal anti-inflammatory drugs (NSAIDs) were commonly cited medications for “usually” or “always” treating pain in children (62% and 67%, respectively), and 19% reported “rarely” or “never” prescribing opioid analgesics in their pediatric practices. Multivariate analyses showed that there were no consistent pediatrician qualities that predicted the use of opioid prescriptions.

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April2010 – Pain Product Announcements & Warnings

Featured Items: hydromorphone extended-release (Exalgo) approval, unapproved nitroglycerin warnings, generic oral transmucosal fentanyl citrate available.
— All brand names are trademarks of their respective manufacturers. Compiled by Winnie Dawson, MA, RN, BSN.

Extended-Release Hydromorphone HCl (Exalgo™) — FDA Approved
Covidien and CombinatoRx announced the March 2010 approval of Exalgo, an extended-release hydromorphone hydrochloride tablet for opioid-tolerant adult patients with moderate to severe chronic pain. This Schedule II mu-opioid agonist uses Alza’s OROS® Push-Pull™ osmotic delivery system to provide a controlled rate of release in a once-daily formulation for patients requiring around-the-clock analgesia. Three dosage strengths were approved: 8 mg, 12 mg, and 16 mg. Exalgo was approved with a risk evaluation and mitigation strategy (REMS) program that requires an education program for healthcare providers and a patient medication guide. For more information, read the Covidien press release and the prescribing information.

Generic Oral Transmucosal Fentanyl Citrate — Now Available
Following FDA approval in October 2009, Covidien has announced the availability of their generic oral transmucosal fentanyl citrate beginning March 2010. The product is equivalent to Actiq(R) — a solid formulation of fentanyl that resembles a lozenge on a stick — and is now available through distributors and retail pharmacies.

Unapproved Nitroglycerin — 2 Makers Receive FDA Warnings
Two makers of unapproved sublingual nitroglycerin tablets — frequently prescribed for chest pain — were ordered to stop marketing their drug products and were given 15 days to respond. The nitroglycerin tablets from Glenmark Generics and Konec come in 0.3 mg, 0.4 mg, and 0.6 mg strengths and have not been FDA-approved for safety and efficacy. This removal warning is part of the FDA's Unapproved Drugs Initiative that was introduced in 2006. Both companies were given 90 days to cease manufacturing and 180 days to halt shipment of existing supplies. Read the FDA press release for more information.