Pain management and awareness have improved considerably (Table 11-5). Gaps, nevertheless, still exist: inadequate understanding of subtypes (Table 26,7) and related treatment implications; inattention to differences among hospice, cognitively impaired, subacute, and elderly and young patients; and limited treatment options for refractory pain.
The Pain Patient
Pain sensation is highly subjective, and individual pain threshold levels differ. Accurate assessment generally requires understanding the patient's pain history, and many programs employ rating scales to measure pain intensity. Cognitive impairment or physical trauma, however, often stifles patients' communication. Cognitively impaired patients may underreport pain frequency and intensity,8 leaving nonverbal cues, like labored breathing, aggression, and agitation, to be the first signs of pain.9 Pain oscillates, especially at night. Caregivers must be especially vigilant for nonverbal cues and document carefully, or oscillations may be confused with treatment response.
Although no ideal agent exists, today's pain treatments include a range of interventions and strategies. Certified pain specialist and geriatric psychiatrist Howard Cohen, MD, director of Dallas Mind/Body Medicine, indicates, "Rational polypharmacy is the rule of thumb when treating chronic pain. Pain is multidimensional, may have visceral, musculoskeletal, or neuropathic origins, and its perception is influenced by psychological factors. For this reason, in addition to NSAIDs [nonsteroidal antiinflammatory drugs] and opioids, multiple adjuvant analgesics with different mechanisms of action, such as anticonvulsants, antidepressants, anesthetics, and other neuropharmacologic agents, are commonly used."
Three recent FDA approvals, including 2 pharmaceuticals and 1 laser device?along with one investigational agent?offer promise.
Pregabalin (Lyrica) is an analogue of gamma-aminobutyric acid with analgesic, anticonvulsant, and anxiolytic activity. Trials for numerous conditions, including diabetic neuropathy,10 postherpetic neuralgia,11 and various anxiety and seizure disorders,12-14 were completed. Some elderly patients with postherpetic neuralgia have now been followed in open-label extensions for 1 and 2 years. No new issues have been identified from these studies. A schedule V controlled substance, pregabalin was associated with more euphoria than placebo during phase 3 clinical trials.
Ziconotide intrathecal (IT) infusion (Prialt) is now available for severe chronic pain in patients intolerant or refractory to other treatments including systemic analgesics, adjunctive agents, or IT morphine. A nonopioid that selectively blocks N-type voltage-sensitive calcium channels, it is given via IT pump implanted by an anesthesiologist and is contraindicated for patients with a history of psychosis. Ziconotide is 1 of only 3 drugs approved for chronic IT use; the others are morphine and baclofen. The pump can stay implanted for several years,with the drug reservoir changed every 40 to 60 days.15,16
Tetrodotoxin (Tectin) is derived from the neurotoxin of the puffer fish (the fish used in fugu sushi; Table 317) and is currently in clinical trials in Canada and Europe for the treatment of severe, refractory cancer pain. Its manufacturer, Wex Pharmaceuticals, intends to seek FDA approval. Dr. Cohen, an early researcher of this sodium channel blocker, indicates, "We have been giving the drug subcutaneously 2 to 3 times a day for 4 days to patients with cancer pain. It is not addictive or habit-forming?patients do not go into withdrawal if we begin tetrodotoxin and stop opioids abruptly. After receiving it for 4 days, some patients have reported pain relief for up to 2 weeks." Tetrodotoxin's side effects have generally been mild and include tingling in the lips (a hallmark of fugu sushi consumption) and some nausea. Doses larger than needed for pain relief tend to cause ataxia. Peripherally acting, it causes no measurable cognitive effects. Its manufacturer is looking at other administration routes.
Recent Canadian clinical trials, however, did not reach their end point.17 Wex researchers intend to focus attention on subsets of cancer patients, as well as noncancer pain, but remain optimistic on the agent's potential. The company anticipates filing a US Investigational New Drug application in 2006, and clinical trials are planned. Regardless of tetrodotoxin's outcome, its underlying science is a promising discovery that may lead to other agents.
PL 5000 Laser
The FDA approved the PL 5000 laser for the treatment of acute and chronic pain, the only laser approved for this use. Unlike high-power lasers used in surgical procedures, the PL 5000 laser produces a low-level, or cold, output and lacks thermal effect on tissue. Along with providing pain relief, the laser stimulates biological functioning, promoting healing, although causal mechanisms remain unknown.18 Sports medicine and athletes have embraced this new technology, finding it especially useful for injuries associated with endurance sports, such as running and biking.
As understanding of pain's etiology broadens, so too will treatment strategies. While many patients dream of a pain-free future, today's arsenal of new agents brings us a step closer to that reality.
Ms. Wick is a senior clinical research pharmacist at the National Cancer Institute, National Institutes of Health. Dr. Zanni is a health-systems consultant and a psychologist based in Alexandria,Va. The views expressed are those of the authors and not those of any government agency.
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One study linked multiple pregnancies to an increased risk of developing atrial fibrillation later in life, and another investigated the association between premature delivery and cardiovascular disease.
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