Should nonsteroidal anti-inflammatory drugs (NSAIDs) be prescribed to the older adult?

The prevalence of chronic pain increases with age, exceeding 50% in individuals aged ≥65 years. Nonsteroidal anti-inflammatory drugs (NSAIDs) are a mainstay of chronic pain management but carry significant dose-related risks of cardiovascular, renal, haematological and other systemic adverse events (AEs). Older patients have an increased risk of these AEs and are more likely to take multiple medications that can potentially interact with NSAIDs. In particular, older patients are more likely to have cardiovascular disease and a natural age-related decline in renal function, increasing the risks of cardiovascular, haematological and renal AEs. Given these risks, recent guidelines for the management of chronic pain in the elderly recommend using NSAIDs rarely and only in carefully selected patients. NSAIDs currently available in the US fall into three categories: nonselective NSAIDs that act via inhibition of cyclo-oxygenase (COX)-1 and COX-2; celecoxib, a selective inhibitor of COX-2; and topical NSAIDs that inhibit both COX-1 and COX-2 but result in much less systemic NSAID exposure than oral formulations. Topical NSAIDs have demonstrated efficacy similar to oral NSAIDs, with an incidence of AEs similar to placebo; however, these agents are an option only in patients with localized pain in superficial joints. Safe pain management in older patients therefore requires cautious choice of selective and nonselective oral NSAIDs, topical NSAIDs or non-NSAID analgesics. This article discusses the risks and benefits of NSAID therapy, reviews its mechanism of action as the source of adverse effects and provides recommendations for maximizing NSAID safety, particularly in older patients. Articles cited in this review were identified via a search of PubMed (January 2005 to November 2009) and a manual search of reference lists from the articles identified in that search. Priority was given to articles discussing NSAID use in older populations, clinical trials of high quality, reports on NSAID safety and AEs, and treatment guidelines.

Antinociception induced by electrical stimulation of spinally projecting noradrenergic neurons in the A7 catecholamine cell group of the rat.

Recent anatomical evidence indicates that the pontine A7 catecholamine cell group provides the major noradrenergic innervation of the spinal cord dorsal horn (laminae I-IV). The experiments described in this report were designed to determine if these neurons modulate nociception at the level of the spinal cord. To this end, the antinociceptive effect of electrical stimulation applied at various sites along several tracks through the dorsolateral pontine tegmentum was determined in lightly anesthetized rats. The latency of the withdrawal response of the hind feet to noxious radiant thermal stimulation applied to the dorsal surface was used as a measure of nociception. The results indicated that the most potent and consistent antinociception was produced at sites near the A7 cell group. In addition, intrathecal injection of alpha-noradrenergic antagonists blocked the antinociception produced by electrical stimulation at sites near the A7 group. These observations indicate that the antinociception produced by stimulation near the A7 cell group was mediated by spinally projecting noradrenergic neurons. The results of these experiments provide evidence that pontospinal noradrenergic neurons located in the A7 cell group are important components of the descending neuronal system that modulates nociception.