Pain in cancer survivors.

Pain is a common problem in cancer survivors, especially in the first few years after treatment. In the longer term, approximately 5% to 10% of survivors have chronic severe pain that interferes with functioning. The prevalence is much higher in certain subpopulations, such as breast cancer survivors. All cancer treatment modalities have the potential to cause pain. Currently, the approach to managing pain in cancer survivors is similar to that for chronic cancer-related pain, pharmacotherapy being the principal treatment modality. Although it may be appropriate to continue strong opioids in survivors with moderate to severe pain, most pain problems in cancer survivors will not require them. Moreover, because more than 40% of cancer survivors now live longer than 10 years, there is growing concern about the long-term adverse effects of opioids and the risks of misuse, abuse, and overdose in the nonpatient population. As with chronic nonmalignant pain, multimodal interventions that incorporate nonpharmacologic therapies should be part of the treatment strategy for pain in cancer survivors, prescribed with the aim of restoring functionality, not just providing comfort. For patients with complex pain issues, multidisciplinary programs should be used, if available. New or worsening pain in a cancer survivor must be evaluated to determine whether the cause is recurrent disease or a second malignancy. This article focuses on patients with a history of cancer who are beyond the acute diagnosis and treatment phase and on common treatment-related pain etiologies. The benefits and harms of the various pharmacologic and nonpharmacologic options for pain management in this setting are reviewed.

Treatment response in antidepressant-naïve postherpetic neuralgia patients: double-blind, randomized trial.

UNLABELLED: In 47 patients with postherpetic neuralgia (PHN) who had never had an adequate trial of any antidepressant, we performed a randomized, double-blind, parallel design trial comparing desipramine, amitriptyline, and fluoxetine. Patients were titrated to a maximum of 150 mg/day for desipramine and amitriptyline and 60 mg/day for fluoxetine over a 3-week period and then treated for an additional 3 weeks before tapering off study medication. A total of 38 subjects (81%) completed the entire trial. The modified intent-to-treat analysis of percent change in daily diary pain intensity scores showed no significant differences among the 3 drugs (ANOVA P = .120). Desipramine produced the greatest reduction in pain intensity (47%), followed by amitriptyline (38%) and fluoxetine (35%). Clinically meaningful pain relief (moderate or better) was significantly more likely with desipramine (12/15 patients) than with amitriptyline (9/17) or fluoxetine (5/15); chi(2)P = 0.036). The 11 subjects using opioids at study entry had smaller reductions in pain than those not using concomitant opioids. The fluoxetine group had the highest noncompletion rate (33%), with 1 subject hospitalized for hyponatremia. Although the magnitude of pain reduction and the category pain relief rating was not significantly different among the 3 drugs, the tricyclics desipramine and amitriptyline were well tolerated and provided clinically meaningful pain relief in 53% to 80% of subjects. PERSPECTIVE: Few clinical trials focus on patients who are naïve to an entire class of medication. In this randomized blinded trial, the tricyclic antidepressants desipramine and amitriptyline were compared to the serotonin-selective antidepressant fluoxetine. All 3 drugs reduced PHN pain, with desipramine providing satisfactory relief in 80% of those treated.

Review of lidocaine patch 5% studies in the treatment of postherpetic neuralgia.

Postherpetic neuralgia (PHN) is a chronic pain syndrome that disproportionately affects the elderly; its incidence is anticipated to increase as the population ages. PHN presents as pain (continuous burning or intense paroxysmal), most often with tactile allodynia, which may be severe and disabling, resulting in poor quality of life and depression. Traditional treatments have included tricyclic antidepressants, anticonvulsants and opioids; however, adverse systemic effects associated with these agents have led to the development of a newer and potentially safer agent, the topical lidocaine patch 5% (Lidoderm), a targeted peripheral analgesic. This article reviews the clinical pharmacology of the lidocaine patch 5% for the treatment of PHN and summarises data from clinical trials of its safety, tolerability and efficacy. The Medline search terms "lidocaine" and "patch" were used to search for English-language articles on the pharmacokinetics of the lidocaine patch 5% and its clinical use for the treatment of PHN. Additional published studies not identified by the database search but performed by the authors or their colleagues were also included in the review. The systemic absorption of lidocaine from the patch was minimal in healthy adults when four patches were applied for up to 24 hours/day, and lidocaine absorption was even lower among PHN patients than healthy adults at the currently recommended dose. Vehicle-controlled and open-label trials found the lidocaine patch 5%, either alone or in combination with other agents, to be effective in the treatment of PHN. Most adverse events were at patch application sites; no clinically significant systemic adverse effects were noted, including when used long term or in an elderly population.In patients with PHN, the lidocaine patch 5% has demonstrated relief of pain and tactile allodynia with a minimal risk of systemic adverse effects or drug-drug interactions. Because of its proven efficacy and safety profile, the lidocaine patch 5% has been recommended as a first-line therapy for the treatment of the neuropathic pain of PHN.

Oral opioid therapy for chronic peripheral and central neuropathic pain.

BACKGROUND: Although opioids are commonly used to treat chronic neuropathic pain, there are limited data to guide their use. Few controlled trials have been performed, and many types of neuropathic pain remain unstudied. METHODS: Adults with neuropathic pain that was refractory to treatment were randomly assigned to receive either high-strength (0.75-mg) or low-strength (0.15-mg) capsules of the potent mu-opioid agonist levorphanol for eight weeks under double-blind conditions. Intake was titrated by the patient to a maximum of 21 capsules of either strength per day. Outcome measures included the intensity of pain as recorded in a diary, the degree of pain relief, quality of life, psychological and cognitive function, the number of capsules taken daily, and blood levorphanol levels. RESULTS: Among the 81 patients exposed to the study drug, high-strength levorphanol capsules reduced pain by 36 percent, as compared with a 21 percent reduction in pain in the low-strength group (P=0.02). On average, patients in the high-strength group took 11.9 capsules per day (8.9 mg per day) and patients in the low-strength group took close to the 21 allowed (18.3 capsules per day; 2.7 mg per day). Affective distress and interference with functioning were reduced, and sleep was improved, but there were no differences between the high-strength group and the low-strength group in terms of these variables. Noncompletion of the study was primarily due to side effects of the opioid. Patients with central pain after stroke were the least likely to report benefit. CONCLUSIONS: The reduction in the intensity of neuropathic pain was significantly greater during treatment with higher doses of opioids than with lower doses. Higher doses produced more side effects without significant additional benefit in terms of other outcome measures.

The lidocaine patch 5% effectively treats all neuropathic pain qualities: results of a randomized, double-blind, vehicle-controlled, 3-week efficacy study with use of the neuropathic pain scale.

BACKGROUND: Several controlled clinical trials have demonstrated the efficacy and safety of the lidocaine patch 5% (LP) for the treatment of postherpetic neuralgia (PHN). OBJECTIVE: To assess the effects of the LP on distinct neuropathic pain qualities common to all neuropathic pain conditions, the authors analyzed data from one of the vehicle-controlled trials in which the Neuropathic Pain Scale (NPS), the only assessment tool specifically designed to measure the distinct components of neuropathic pain, was administered. METHODS AND RESULTS: To improve the sensitivity of the NPS to treatment effects, only patients who, at the time of enrollment in the study, reported moderate-to-severe pain on the NPS (as defined by a score > or =4/10 reported for at least 6 of the 10 individual NPS items) were included in the analysis. Thus, 96 patients were included in this analysis. After a 3-week, vehicle-controlled study, LP improved all assessed pain qualities to a greater extent than the placebo patch, as measured by the NPS 10, a sum score including all 10 NPS item scores ( = 0.043), and an NPS 8 score, which included scores for all 8 pain descriptors, excluding "unpleasantness" and "global intensity" ( = 0.042). Separate analysis of all 8 items believed not to reflect allodynia (NPS NA; excluding "skin sensitivity" and "surface pain") also demonstrated superiority ( = 0.022), as did analysis of the subitems that are believed not to be primarily related to peripheral pathophysiological events (the "NPS 4": "sharp," "hot," "dull," and "deep" pains; = 0.013). CONCLUSIONS: This study demonstrates that LP reduces the intensity of all common neuropathic pain qualities and thus may be of potential benefit for nonallodynic neuropathic pain states. Furthermore, these findings suggest that peripheral mechanisms may play a role in the pathophysiological development of pain qualities that heretofore have been assumed not to involve peripheral mechanisms, such as "dull," "deep," "sharp," and "burning" pains.

Lidocaine patch: double-blind controlled study of a new treatment method for post-herpetic neuralgia.

Post-herpetic neuralgia (PHN) is a common and often intractable neuropathic pain syndrome predominantly affecting the elderly. Topical local anesthetics have shown promise in both uncontrolled and controlled studies. Thirty-five subjects with established PHN affecting the torso or extremities completed a four-session, random order, double-blind, vehicle-controlled study of the analgesic effects of topically applied 5% lidocaine in the form of a non-woven polyethylene adhesive patch. All subjects had allodynia on examination. Up to 3 patches, covering a maximum of 420 cm2, were applied to cover the area of greatest pain as fully as possible. Lidocaine containing patches were applied in two of the four 12-h-long sessions, in one session vehicle patches were applied, and one session was a no-treatment observation session. Lidocaine containing patches significantly reduced pain intensity at all time points 30 min to 12 h compared to no-treatment observation, and at all time points 4--12 h compared to vehicle patches. Lidocaine patches were superior to both no-treatment observation and vehicle patches in averaged category pain relief scores. The highest blood lidocaine level measured was 0.1 micrograms/ml, indicating minimal systemic absorption of lidocaine. Patch application was without systemic side effect and well tolerated when applied on allodynic skin for 12 h. This study demonstrates that topical 5% lidocaine in patch form is easy to use and relieves post-herpetic neuralgia.