Original Article
Oral Opioid Therapy for Chronic Peripheral and Central Neuropathic Pain
N Engl J Med 2003; 348:1223-1232March 27, 2003
- Abstract
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 μ-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.
Media in This Article
Figure 1
Course of the Study.Figure 2
Time Course of Intensity of Pain as Measured on the Visual-Analogue Scale (Panel A), of Categorical Ratings of Pain Relief (Panel B), and of Capsule Intake per Day (Panel C).Article Activity
- Article
Opioids, although frequently prescribed, remain a controversial treatment for chronic neuropathic pain.1-7 Studies in animals and some studies in humans have suggested that chronic neuropathic pain may respond poorly to opioid therapy,2,3,8 but placebo-controlled studies of brief intravenous infusions have demonstrated analgesia.9,10 Oral controlled-release opioids have been reported to be superior to placebo for postherpetic neuralgia, but the responsiveness to opioids of many types of neuropathic pain, including the pain syndromes that follow central nervous system injuries and are considered to be especially difficult to manage, have not been evaluated in a blinded, prospective manner.5,6,11-13
There are important issues with respect to the design of such trials. First, it is difficult to use a placebo control group, since the patients receiving placebo will have unrelieved chronic pain. In trials in which opioids are active treatments, their side effects can easily reveal the treatment-group assignment to which patients are initially blinded. “Active placebo” agents, such as lorazepam or benztropine, may improve blinding but may produce serious adverse effects, especially in the elderly. Therefore, we took advantage of the dose-dependent nature of opioid analgesia to test efficacy by comparing two different doses under randomized, double-blind conditions in an eight-week study involving patients with neuropathic pain of central or peripheral origin.14 Within preset limits for capsule intake, patients titrated their own doses to attain the optimal balance between pain relief and side effects. The potent μ-opioid agonist levorphanol was chosen for its six-to-eight-hour duration of analgesic action, relatively simple pharmacokinetics, and receptor selectivity.14-17
Methods
Study Design
Patients were randomly assigned to receive either low-strength (0.15-mg) or high-strength (0.75-mg) levorphanol capsules. As shown in Figure 1Figure 1
Course of the Study., after a one-week period for the collection of base-line data, patients received levorphanol therapy for eight weeks, after which the doses were tapered over a period of one to four weeks. Within the limits of safety and tolerability, patients could titrate their doses up to 21 capsules per day (7 capsules three times a day) by the end of the fourth week of treatment. Maximal allowable doses were therefore 3.15 mg per day in the low-strength group and 15.75 mg per day in the high-strength group. The study was approved by the institutional review board at the University of California, San Francisco, and the California Research Advisory Panel. Written informed consent was obtained from all patients.Study Patients
Adults with neuropathic pain due to confirmed peripheral neuropathy or focal nerve injury, postherpetic neuralgia, spinal cord injury with incomplete myelopathy, central pain following a stroke or focal brain lesion, or clinically definite multiple sclerosis were recruited by advertisements and referrals from physicians. Criteria for exclusion included previous opioid therapy exceeding 360 mg of codeine per day or the equivalent; allergy to levorphanol; another pain problem of equal or greater severity; cognitive impairment; ongoing major depression with a risk of suicide; antisocial or borderline personality disorder; unstable health; clinically significant liver, renal, or pulmonary disease; sleep apnea; active treatment for cancer; immunosuppression due to drugs or disease; current drug or alcohol abuse; and history of opioid abuse. Procedures for screening visits included medical history taking, physical examination, evaluation by a psychologist (including neuropsychological testing and the Structured Clinical Interview of the Diagnostic and Statistical Manual of Mental Disorders, fourth edition),18 routine hematologic and chemical analyses, and testing of urine for drugs of abuse.
Outcome Measures
Patients used a daily diary to score their pain daily on a visual-analogue scale labeled “no pain” at 0 mm and “worst pain imaginable” at 100 mm. Each evening, patients rated the average intensity of their pain during the preceding 24 hours.19 Each patient used a categorized pain-relief scale to score the pain relief achieved since beginning study treatment; on this scale, 0 indicated “worse” pain, 1 “no pain relief,” 2 “slight” pain relief, 3 “moderate” pain relief, 4 “a lot” of pain relief, and 5 “complete” pain relief.19 In addition, patients completed several other assessments at the beginning of the study and thereafter as noted below. These assessments included the Profile of Mood States, which includes 65 items rated from 0 to 4 and scored in terms of total mood disturbance20; the Multidimensional Pain Inventory, a 61-item inventory entailing 13 empirically derived scales and assessing the effect of pain on quality of life, perceived social support, and ability to engage in daily activities21; the Symbol–Digit Modalities Test, which assesses attention or concentration and immediate recall through verbal matching of meaningless geometric designs with a number key22; and the Opiate-Agonist Effects Scale and Opiate Withdrawal Scale, 16-item and 21-item questionnaires on which patients rate symptoms related to agonist and antagonist activity on a 0-to-4 scale.23
Study Visits and Treatment
After the screening visit, study visits took place at the start of the base-line week; the beginning of the first, second, fourth, sixth, and eighth weeks of treatment; at the initiation of the tapering of the dose of the study drug; in the middle of the tapering period; and at the end of the study (Figure 1). Patients kept a daily diary to record their intake of study capsules, their use of concomitant medications, and their daily pain on the visual-analogue scale described above. Patients were contacted by telephone every 7 to 14 days so that investigators could monitor compliance and safety. After complete discontinuation of previous opioid use (if any) for at least one week, the base-line evaluation took place, including repeated urine testing for opioids. Procedures at subsequent study visits included measurement of vital signs, physical examination, review of the daily diary, counting of levorphanol capsules, and the completion of the assessments described above. Patients began taking the study drug at the visit at the beginning of week 1 if their average daily pain according to the diary scale exceeded 25 mm during the base-line week. They continued to receive all other medical treatments and stable nonopioid therapies for pain, but were not allowed to begin any new treatments for pain.
Randomization was stratified according to sex, age (≤70 years or >70 years), and diagnosis (peripheral neuropathy or focal nerve injury, postherpetic neuralgia, central pain following stroke or focal brain lesion, spinal cord injury, or multiple sclerosis). Low-strength capsules and high-strength capsules were identical in appearance and were packaged in patient-specific bottles. Maximal total daily intake was 3 capsules during week 1 of treatment, 9 capsules during week 2, 15 capsules during week 3, and 21 capsules from week 4 through the end of week 8. The minimal dose was one capsule per day. Throughout the study, patients were encouraged to find the optimal balance between pain reduction and side effects within the limits of the protocol. The visit at the beginning of week 8 also included screening of urine for opioids, an interview with a psychologist, and measurement of the blood levorphanol level.24 On completion of eight weeks of treatment or at the time of withdrawal from the study, patients tapered their dose of levorphanol to zero over a period of one to four weeks.
Statistical Analysis
Base-line demographic variables were compared by Fisher's exact test or an unpaired t-test. The primary outcome measure was the change in the weekly averages of the daily ratings of pain on the visual-analogue scale from the base-line week through the eighth week of treatment before the tapering of the dose of the study drug. The primary outcome measure of the mean pain ratings for the two treatment groups was tested with the use of a repeated-measures, mixed-effects model for longitudinal data.25 This procedure allowed the use of all data collected from all patients exposed to the study drug without the exclusion of patients from the analysis or the imputation of missing data. As a secondary analysis, we reestimated the model using the base-line scores on the visual-analogue scale as an additional covariate.
Secondary measures analyzed in the group of all patients exposed to the study drug included the category of pain relief (analyzed by unpaired t-test), maximal weekly capsule intake (by unpaired t-test), and change from base line to the last week of treatment for the Profile of Mood States, Symbol–Digit Modalities Test, Opiate-Agonist Effects Scale, and Opiate Withdrawal Scale (all by analysis of covariance). Results on the Multidimensional Pain Inventory were analyzed (by analysis of covariance) only for patients who completed the study (patients who continued therapy with the study drug through week 8). P values of less than 0.05 were considered to indicate statistical significance. No interim analyses were scheduled or performed.
Results
Study Patients
A total of 100 patients were recruited, but 19 did not undergo randomization and did not receive study medication (14 withdrew consent, 1 had pain scores below the minimal level, and 4 were excluded after the psychological evaluation). Of 81 patients who received levorphanol, the 43 randomly assigned to high-strength capsules and the 38 assigned to low-strength capsules were similar with respect to sex, age, race, cause of pain, average daily pain at base line, and duration of pain (Table 1Table 1
Demographic and Base-Line Characteristics of the Patients.). Twenty-three patients had pain originating in the central nervous system (central pain following stroke or focal brain lesion, spinal cord injury, or multiple sclerosis), and 58 had pain originating in the peripheral nervous system (peripheral neuropathy, focal nerve injury, or postherpetic neuralgia).In all patients, one or more previous trials of nonopioid medications had failed to relieve the pain. Thirty-seven patients (46 percent) had previously tried low-dose opioids, and in 16 of these patients, the doses of previously used opioids had to be tapered before study entry. There was a trend toward previous use of low-dose opioids in the low-strength group (P for trend = 0.06). Thirty-two patients did not use concomitant medications, and 23 used more than one type of concomitant medications. The most common types of concomitant medications were antidepressants (in 24 patients), nonsteroidal antiinflammatory drugs (in 24 patients), and anticonvulsants (in 11 patients). Although patients in the low-strength group were more likely to use concomitant medications for control of pain (P=0.03), the proportion using each specific type of concomitant medication was similar in the two groups.
Primary Outcome Measure
The intensity of pain as judged by the ratings on the visual-analogue scale during the base-line week was moderately severe in both groups (mean [±SD] in the high-strength group, 65.4±18.2 mm; mean in the low-strength group, 69.3±17.0 mm; P=0.33). The degree of reduction of pain was significantly greater in the high-strength group (a 36 percent reduction to 42.1±26.5 mm) than in the low-strength group (a 21 percent reduction to 53.4±24.7 mm, P=0.02) (Figure 2AFigure 2
Time Course of Intensity of Pain as Measured on the Visual-Analogue Scale (Panel A), of Categorical Ratings of Pain Relief (Panel B), and of Capsule Intake per Day (Panel C).). The addition of the base-line visual-analogue score as a covariate in statistical models did not alter this result.Secondary Outcome Measures
Figure 2B shows the time course of categorized ratings of pain relief. Differences between the treatment groups were greatest at the week 2 visit (P=0.07) but then declined steadily (P=0.31 for the difference at week 8). Among all patients exposed to the study drug in the high-strength group, 47 percent reported pain relief that was moderate or better at the end of treatment. Among those who completed the study taking high-strength capsules, there was a 48 percent reduction in pain, and the proportion reporting pain relief that was moderate or better was 66 percent. Among all patients who completed the study, the ratio of the mean blood levorphanol level in the high-strength group at week 8 (4.8 ng per milliliter) to the mean level in the low-strength group (1.4 ng per milliliter) closely mirrored the ratio of the actual levels of levorphanol intake.
A total of 59 patients completed eight weeks of levorphanol therapy — 67 percent in the high-strength group and 79 percent in the low-strength group (P=0.32). Patients in the high-strength group took significantly fewer capsules each day (11.9±5.5 vs. 18.3±4.3 capsules per day, P<0.001) (Figure 2C). Patients assigned to high-strength capsules took a mean dose of 8.9 mg per day, and patients assigned to low-strength capsules took a mean dose of 2.7 mg per day. As shown in Figure 3Figure 3
Box Plot of Maximal Daily Dose in All Patients Exposed to the Study Drug., there was a broad range of capsule intake in each group, but there was minimal overlap in actual levorphanol intake, since all but six patients in the high-strength group exceeded 3.15 mg per day.There was no significant change in total mood disturbance (according to the Profile of Mood States) during the study in either treatment group. Cognitive impairment was not apparent, and scores on the Symbol–Digit Modalities Test actually improved in both treatment groups. Although results on the Multidimensional Pain Inventory among patients who completed the study (Table 2Table 2
Results on the Multidimensional Pain Inventory among the 59 Patients Who Completed the Study.) showed significant reductions over the course of the trial in the severity of pain, interference in functioning, and affective distress, as well as a significant improvement in the ability to “get enough sleep,” there were no significant differences between the two treatment groups in terms of any of the scales in the inventory.The intensity of pain decreased during treatment in every subgroup defined according to the cause of pain (Table 3Table 3
Change in the Intensity of Diary-Recorded Pain as Measured on the Visual-Analogue Scale, According to Diagnosis.). The advantage of high-strength capsules over low-strength capsules was most apparent in the subgroups with postherpetic neuralgia, spinal cord injury, and multiple sclerosis. The degree of pain reduction during treatment with levorphanol did not vary significantly according to whether patients had previously used opioids or according to whether they used concomitant nonopioid medications. Older age and longer duration of pain were not associated with smaller reductions in pain. Reductions in pain during levorphanol therapy were reversed during the period of tapering of the doses, when patients remained unaware of their treatment-group assignment. By the last seven days of the tapering period, the intensity of pain had returned to 96 percent of the base-line levels. Those who completed the study took an average of 17 days to stop taking levorphanol completely.Withdrawal from the Study and Adverse Events
No base-line measure significantly predicted which patients would withdraw from the study, but 7 of 10 patients with central pain due to a stroke or focal brain lesion did not complete the study. Reasons for withdrawal from the study included physical or psychological adverse events in 15 patients (12 in the high-strength group and 3 in the low-strength group, P=0.06), treatment failure in 3 patients, lack of adherence to the protocol in 1 patient, and other reasons in 3 patients. According to their self-ratings while they were still taking the study drug, those who later withdrew from the study were less talkative (P=0.001), more restless (P=0.007), and more depressed (P=0.005) than patients who went on to complete the study. At the time of withdrawal from the study, these patients were taking fewer capsules than those who went on to complete the study and had a mean reduction in pain of only 10 percent.
No serious or unexpected drug-related adverse events occurred. One death due to long-standing cardiovascular disease occurred in the low-strength group. Opioid-agonist effects measured on the subscales entitled “Dry Mouth,” “Itchy Skin,” “Sweating,” “Sleepy,” “Noise,” “Carefree,” and “Drunken” increased during treatment in both treatment groups. As compared with patients in the low-strength group, those in the high-strength group reported significantly greater effects with regard to “Itchy Skin,” “Sweating,” and “Skin Clammy.” Some adverse effects were reported only by patients in the high-strength group, including anger, irritability, or mood or personality change in six patients, generalized weakness or confusion in five patients, and dizziness or loss of equilibrium in two patients. One patient had suicidal ideation because of worsening pain during the tapering period, and her primary physician decided to continue levorphanol therapy.
Discussion
This double-blind dose–response study demonstrates that the reduction in neuropathic pain achieved with higher doses of the potent opioid levorphanol (through the use of a higher-strength preparation) was significantly greater than the reduction achieved with lower doses (pain reduction, 36 percent vs. 21 percent). Patients randomly assigned to low-strength levorphanol capsules took close to the maximal number of capsules allowed. However, the mean opioid intake in the low-strength group, 2.7 mg per day, is far from a placebo level. In patients receiving repeated doses, 3 mg of levorphanol is equivalent to as much as 45 to 90 mg of oral morphine or 30 to 45 mg of oral oxycodone — the latter being a dose that has been shown in a placebo-controlled study to relieve postherpetic neuralgia.12
We chose a dose–response design over a placebo-controlled study for several reasons. Opioids are already an approved therapy for pain, and enrolled patients had severe daily pain originating in the central or peripheral nervous system despite having access to nonopioid medications for pain control. The distinctive side effects of opioids make it difficult to maintain blinding with the use of an inactive placebo, and “active” placebos carry their own risks of adverse effects. Without a placebo control group, the reductions in pain cannot be attributed to the effects of the opioids. The significant differences in pain reduction between the study groups and the return to the base-line levels of pain after the discontinuation of opioid treatment strongly suggest that higher-dose opioids effectively reduce the intensity of chronic neuropathic pain. As compared with a placebo-controlled study, a dose–response study is less able to show differences between treatment groups in complex measures that may be less responsive to opioid therapy, such as mood and quality of life. In our study, the advantage of high-strength capsules was limited to improved pain reduction.
High rates of withdrawal from the study, mostly because of side effects, have been reported before in studies of opioids for neuropathic pain. In a placebo-controlled crossover trial of oxycodone for postherpetic neuralgia, 24 percent of patients did not complete the trial.12 Recently, Raja and colleagues compared controlled-release morphine with the tricyclic antidepressant nortriptyline and a placebo in patients with postherpetic neuralgia.13 Although pain reduction with morphine was superior to that with placebo, and there was a trend toward superiority to that with nortriptyline, patients in that study were much more likely to withdraw during the opioid-therapy phase. In our study, patients were encouraged to find the optimal balance between pain reduction and adverse effects and could remain in the study by taking as little as one capsule per day. A long titration period and a strict upper limit for capsule intake were used to protect the patients, many of whom were elderly or partially disabled or had not previously taken opioids. Despite these measures, 27 percent of patients withdrew. Furthermore, anger, irritability, and personality changes were reported only by patients in the high-strength group, and more patients in this group withdrew from the study. On the basis of our findings, it is clear that not all patients will benefit from opioids, and some will have worsening of mood and function without relief of pain.
The belief that tolerance to opioid analgesics quickly eliminates any initial analgesic benefit remains widespread.26-28 Retrospective and open-label prospective studies have not adequately addressed the important issue of tolerance.29-33 Moulin and colleagues compared controlled-release morphine with placebo in 61 patients with musculoskeletal pain.34 Pain reduction of about 25 percent occurred during the initial three-week titration period but was largely lost during the subsequent six-week period of administration of stable doses. In our study, daily capsule intake and ratings of intensity of pain were stable during the last two weeks of therapy, suggesting that there was no tolerance in the form of a loss of analgesic efficacy that might be reflected in a rapid escalation of doses. There was no addictive behavior observed. In fact, only four patients in the high-strength group ever reached the maximal capsule intake allowed. However, prospective, controlled studies assessing the stability of pain control and dose requirements over periods of many months to years are needed.
The magnitude of the reduction in neuropathic pain achieved with high-strength levorphanol capsules is similar to that reported in placebo-controlled studies of tricyclic antidepressants and the anticonvulsant gabapentin. A placebo-controlled trial of eight weeks of treatment with gabapentin in 229 patients with postherpetic neuralgia reported a 33 percent reduction in the intensity of pain and moderate or better pain relief in 50 percent of patients.35 In our study, which included patients with central pain, the intensity of pain decreased by 36 percent during therapy with high-strength levorphanol, and moderate or better pain relief was achieved in 47 percent of patients. Our results showing a 48 percent reduction in pain and moderate or better pain relief in 66 percent of patients in the high-strength group who completed the study are almost identical to results reported in four controlled trials of tricyclic antidepressants for peripheral neuropathy and postherpetic neuralgia in which only the data from patients who completed the study were analyzed.18,36-38 In summary, higher doses of the opioid levorphanol are more effective than low doses in reducing the intensity of chronic neuropathic pain originating in the central or peripheral nervous system, but in many patients, pain relief is not achieved or there are intolerable side effects.
Supported by the National Institute on Drug Abuse (project DA-01696) and the National Institute of Neurological Disorders and Stroke (Pain Research Training grant NS07625, grant K24-NS02164, and project NS21445).
Dr. Rowbotham reports having received fees for consulting from Allergan, Biogen, Grunenthal, King Pharmaceuticals–Lineberry Research, Ortho–McNeil–Johnson & Johnson, Pfizer, Schwarz BioSciences, and WinPharm; lecturing on behalf of Pfizer and Novartis; having received grant support from UCB Pharma, Johnson & Johnson, Endo Pharmaceuticals, and Pfizer; and having received royalties from Hind Health Care for a topical local anesthetic patch. Ms. Davies reports having received consulting fees from Endo Pharmaceuticals. Dr. Taylor reports owning stock in Pfizer. Dr. Mohr reports having received grant support from Biogen.
We are indebted to Erika Friedman, Christina Verkempinck, R.N., Barth Wilsey, M.D., Bokgi Choi, M.D., Robert Cluff, M.D., Karin Petersen, M.D., Reese Jones, M.D., Tom Everhart, Ph.D., Kaye Welch, and Kevin Delucchi, Ph.D., for their valuable contributions.
Source Information
From the Pain Clinical Research Center, Department of Neurology (M.C.R., L.T., P.S.D., L.R., K.T., D.M.), and the Department of Anesthesia (M.C.R.), University of California, San Francisco, School of Medicine; and the University of California, San Francisco, School of Pharmacy (L.R.) — all in San Francisco.
Address reprint requests to Dr. Rowbotham at the Pain Clinical Research Center, 1701 Divisadero St., Ste. 480, San Francisco, CA 94115.
- References
References
1
Dubner R . A call for more science, not more rhetoric, regarding opioids and neuropathic pain. Pain 1991;47:1-2
CrossRef | Web of Science | Medline2
Fields HL . Can opiates relieve neuropathic pain? Pain 1988;35:365-367
CrossRef | Web of Science | Medline3
Arner S ,Meyerson BA . Lack of analgesic effect of opioids on neuropathic and idiopathic forms of pain. Pain 1988;33:11-23
CrossRef | Web of Science | Medline4
Arner S ,Meyerson BA . Genuine resistance to opioids -- fact or fiction? Pain 1991;47:116-121
CrossRef | Web of Science | Medline5
Dellemijn P . Are opioids effective in relieving neuropathic pain? Pain 1999;80:453-462
CrossRef | Web of Science | Medline6
McQuay HJ . Opioid use in chronic pain. Acta Anaesthesiol Scand 1997;41:175-183
CrossRef | Web of Science | Medline7
Wall PD . Neuropathic pain. Pain 1990;43:267-268
CrossRef | Web of Science | Medline8
Portenoy RK ,Foley KM ,Inturrisi CE . The nature of opioid responsiveness and its implications for neuropathic pain: new hypotheses derived from studies of opioid infusions. Pain 1990;43:273-286
CrossRef | Web of Science | Medline9
Rowbotham MC ,Reisner-Keller LA ,Fields HL . Both intravenous lidocaine and morphine reduce the pain of postherpetic neuralgia. Neurology 1991;41:1024-1028
Web of Science | Medline10
Dellemijn PL ,Vanneste JA . Randomised double-blind active-placebo-controlled crossover trial of intravenous fentanyl in neuropathic pain. Lancet 1997;349:753-758
CrossRef | Web of Science | Medline11
Rowbotham MC. The debate over opioids and neuropathic pain. In: Kalso E, Wiesenfeld-Hallin Z, McQuay HJ, eds. Opioid sensitivity of chronic noncancer pain. Vol. 14 of Progress in pain research and management. Seattle: IASP Press, 1999:307-18.
12
Watson CP ,Babul N . Efficacy of oxycodone in neuropathic pain: a randomized trial in postherpetic neuralgia. Neurology 1998;50:1837-1841
Web of Science | Medline13
Raja SN ,Haythornthwaite JA ,Pappagallo M , et al. Opioids versus antidepressants in postherpetic neuralgia: a randomized, placebo-controlled trial. Neurology 2002;59:1015-1021
Web of Science | Medline14
Morgan D ,Cook CD ,Smith MA ,Picker MJ . An examination of the interactions between the antinociceptive effects of morphine and various mu-opioids: the role of intrinsic efficacy and stimulus intensity. Anesth Analg 1999;88:407-413
CrossRef | Web of Science | Medline15
Dixon R ,Crews T ,Inturrisi C ,Foley K . Levorphanol: pharmacokinetics and steady-state plasma concentrations in patients with pain. Res Commun Chem Pathol Pharmacol 1983;41:3-17
Medline16
Morrison JD ,Loan WB ,Dundee JW . Controlled comparison of the efficacy of fourteen preparations in the relief of postoperative pain. Br Med J 1971;3:287-290
CrossRef | Web of Science | Medline17
Banister EH . Six potent analgesic drugs: a double-blind study in post-operative pain. Anaesthesia 1974;29:158-162
CrossRef | Web of Science | Medline18
First MB, Gibbon M, Spitzer RL, Williams JBW. Structured Clinical Interview for DSM-IV-TR. New York: New York State Psychiatric Institute, 1995. (Also available at http://cpmcnet.columbia.edu/dept/scid/.)
19
Max MB ,Culnane M ,Schafer SC , et al. Amitriptyline relieves diabetic neuropathy pain in patients with normal or depressed mood. Neurology 1987;37:589-596
Web of Science | Medline20
McNair DM, Lorr M, Droppleman LF. Manual for the Profile of Mood States (POMS). San Diego, Calif.: Educational and Industrial Testing Service, 1971.
21
Kerns RD ,Turk DC ,Rudy TE . The West Haven-Yale Multidimensional Pain Inventory (WHYMPI). Pain 1985;23:345-356
CrossRef | Web of Science | Medline22
Smith A. Symbol-Digit Modalities Test. Los Angeles: Western Psychological Services, 1991. (Also available at http://www.tvtc.com:8080/tvtc/tvtcpage/sdmt.html.)
23
Preston KL ,Bigelow GE ,Liebson IA . Comparative evaluation of morphine, pentazocine and ciramadol in postaddicts. J Pharmacol Exp Ther 1987;240:900-910
Web of Science | Medline24
Everhart ET ,Shwonek P ,Jacob P III ,Rowbotham MC ,Jones RT . Quantitation of levorphanol in human plasma at subnanogram per milliliter levels using capillary gas chromatography with electron-capture detection. J Chromatogr B Biomed Sci Appl 1999;729:173-181
CrossRef | Medline25
Littell RC ,Pendergast J ,Natarajan R . Modelling covariance structure in the analysis of repeated measures data. Stat Med 2000;19:1793-1819
CrossRef | Web of Science | Medline26
Gilson AM ,Joranson DE . Controlled substances and pain management: changes in knowledge and attitudes of state medical regulators. J Pain Symptom Manage 2001;21:227-237
CrossRef | Web of Science | Medline27
Joranson DE . Federal and state regulation of opioids. J Pain Symptom Manage 1990;5:Suppl:S12-S23
Medline28
Joranson DE ,Gilson AM . Regulatory barriers to pain management. Semin Oncol Nurs 1998;14:158-163
CrossRef | Medline29
Maruta T ,Swanson DW ,Finlayson RE . Drug abuse and dependency in patients with chronic pain. Mayo Clin Proc 1979;54:241-244
Web of Science | Medline30
France RD ,Urban BJ ,Keefe FJ . Long-term use of narcotic analgesics in chronic pain. Soc Sci Med 1984;19:1379-1382
CrossRef | Web of Science | Medline31
Dellemijn PL ,van Duijn H ,Vanneste JA . Prolonged treatment with transdermal fentanyl in neuropathic pain. J Pain Symptom Manage 1998;16:220-229
CrossRef | Web of Science | Medline32
Porter J ,Jick H . Addiction rare in patients treated with narcotics. N Engl J Med 1980;302:123-123
Web of Science | Medline33
Watson CP ,Evans RJ ,Watt VR ,Birkett N . Post-herpetic neuralgia: 208 cases. Pain 1988;35:289-297
CrossRef | Web of Science | Medline34
Moulin DE ,Iezzi A ,Amireh R ,Sharpe WK ,Boyd D ,Merskey H . Randomised trial of oral morphine for chronic non-cancer pain. Lancet 1996;347:143-147
CrossRef | Web of Science | Medline35
Rowbotham M ,Harden N ,Stacey B ,Bernstein P ,Magnus-Miller L . Gabapentin for the treatment of postherpetic neuralgia: a randomized controlled trial. JAMA 1998;280:1837-1842
CrossRef | Web of Science | Medline36
Kishore-Kumar R ,Max MB ,Schafer SC , et al. Desipramine relieves postherpetic neuralgia. Clin Pharmacol Ther 1990;47:305-312
CrossRef | Web of Science | Medline37
Max MB ,Schafer SC ,Culnane M ,Smoller B ,Dubner R ,Gracely RH . Amitriptyline, but not lorazepam, relieves postherpetic neuralgia. Neurology 1988;38:1427-1432
Web of Science | Medline38
Max MB ,Lynch SA ,Muir J ,Shoaf SE ,Smoller B ,Dubner R . Effects of desipramine, amitriptyline, and fluoxetine on pain in diabetic neuropathy. N Engl J Med 1992;326:1250-1256
Full Text | Web of Science | Medline
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CrossRef8
Jane E. Loitman. (2011) Levorphanol #240. Journal of Palliative Medicine 14:7, 875-876
CrossRef9
John A. Snowden, Sam H. Ahmedzai, John Ashcroft, Shirley D’Sa, Timothy Littlewood, Eric Low, Helen Lucraft, Rhona Maclean, Sylvia Feyler, Guy Pratt, Jennifer M. Bird, . (2011) Guidelines for supportive care in multiple myeloma 2011. British Journal of Haematology 154:1, 76-103
CrossRef10
Doralina L. Anghelescu, Linda L. Oakes, Gisele M. Hankins. (2011) Treatment of Pain in Children after Limb-Sparing Surgery: An Institution's 26-Year Experience. Pain Management Nursing 12:2, 82-94
CrossRef11
Peggy Compton. (2011) Treating Chronic Pain with Prescription Opioids in the Substance Abuser: Relapse Prevention and Management. Journal of Addictions Nursing 22:1-2, 39-45
CrossRef12
Judith A. Paice. 2011. Management of pain at end of life. , 520-524.
CrossRef13
Chad M. Brummett, Srinivasa N. Raja. 2011. Central pain states. , 370-377.
CrossRef14
Eu-Teum Hahm, Younghoon Kim, Jong-Ju Lee, Young-Wuk Cho. (2011) GABAergic synaptic response and its opioidergic modulation in periaqueductal gray neurons of rats with neuropathic pain. BMC Neuroscience 12:1, 41
CrossRef15
Evan D. Kharasch. (2011) Intraoperative Methadone. Anesthesia & Analgesia 112:1, 13-16
CrossRef16
Gunnar Wasner. (2010) Central Pain Syndromes. Current Pain and Headache Reports 14:6, 489-496
CrossRef17
Andrew C. Gallo, Vincent T. Codispoti. (2010) Complex Regional Pain Syndrome Type II Associated with Lumbosacral Plexopathy: A Case Report. Pain Medicine 11:12, 1834-1836
CrossRef18
TM Largent-Milnes, T Yamamoto, P Nair, JW Moulton, VJ Hruby, J Lai, F Porreca, TW Vanderah. (2010) Spinal or systemic TY005, a peptidic opioid agonist/neurokinin 1 antagonist, attenuates pain with reduced tolerance. British Journal of Pharmacology 161:5, 986-1001
CrossRef19
N. Attal, G. Cruccu, R. Baron, M. Haanpää, P. Hansson, T. S. Jensen, T. Nurmikko. 2010. Treatment of Neuropathic Pain. , 399-410.
CrossRef20
N. Attal, G. Cruccu, R. Baron, M. Haanpää, P. Hansson, T. S. Jensen, T. Nurmikko. (2010) EFNS guidelines on the pharmacological treatment of neuropathic pain: 2010 revision. European Journal of Neurology 17:9, 1113-e88
CrossRef21
Steven Ganzberg. (2010) Pain Management Part II: Pharmacologic Management of Chronic Orofacial Pain. Anesthesia Progress 57:3, 114-119
CrossRef22
Ilaria Spoletini, Carlo Caltagirone, Moira Ceci, Walter Gianni, Gianfranco Spalletta. (2010) Management of pain in cancer patients with depression and cognitive deterioration. Surgical Oncology 19:3, 160-166
CrossRef23
Nanna Brix Finnerup, Søren Hein Sindrup, Troels Staehelin Jensen. (2010) The evidence for pharmacological treatment of neuropathic pain. PAIN 150:3, 573-581
CrossRef24
Dwight E. Moulin, Ute Richarz, Mark Wallace, Adam Jacobs, John Thipphawong. (2010) Efficacy of the Sustained-Release Hydromorphone in Neuropathic Pain Management: Pooled Analysis of Three Open-Label Studies. Journal of Pain and Palliative Care Pharmacotherapy 24:3, 200-212
CrossRef25
Sally Elizabeth Kendall, Per Sjøgren, Cibele Andrucioli de Mattos Pimenta, Jette Højsted, Geana Paula Kurita. (2010) The cognitive effects of opioids in chronic non-cancer pain. PAIN 150:2, 225-230
CrossRef26
Sushma Bhatnagar, Seema Mishra, S. Roshni, Vikas Gogia, Sandeep Khanna. (2010) Neuropathic Pain in Cancer Patients—Prevalence and Management in a Tertiary Care Anesthesia-Run Referral Clinic Based in Urban India. Journal of Palliative Medicine 13:7, 819-824
CrossRef27
Turo J. Nurmikko, Sameer Gupta, Kate Maclver. (2010) Multiple Sclerosis-Related Central Pain Disorders. Current Pain and Headache Reports 14:3, 189-195
CrossRef28
Robert H. Dworkin, Dennis C. Turk, Sarah Peirce-Sandner, Ralf Baron, Nicholas Bellamy, Laurie B. Burke, Amy Chappell, Kevin Chartier, Charles S. Cleeland, Ann Costello, Penney Cowan, Rozalina Dimitrova, Susan Ellenberg, John T. Farrar, Jacqueline A. French, Ian Gilron, Sharon Hertz, Alejandro R. Jadad, Gary W. Jay, Jarkko Kalliomäki, Nathaniel P. Katz, Robert D. Kerns, Donald C. Manning, Michael P. McDermott, Patrick J. McGrath, Arvind Narayana, Linda Porter, Steve Quessy, Bob A. Rappaport, Christine Rauschkolb, Bryce B. Reeve, Thomas Rhodes, Cristina Sampaio, David M. Simpson, Joseph W. Stauffer, Gerold Stucki, Jeffrey Tobias, Richard E. White, James Witter. (2010) Research design considerations for confirmatory chronic pain clinical trials: IMMPACT recommendations. PAIN 149:2, 177-193
CrossRef29
C. Maihöfner, F. Seifert, K. Markovic. (2010) Complex regional pain syndromes: new pathophysiological concepts and therapies. European Journal of Neurology 17:5, 649-660
CrossRef30
Alec B. O'Connor, Robert H. Dworkin. 2010. Clinical Trial Design for Chronic Pain Treatments. , 14-30.
CrossRef31
Kristina B. Svendsen, Nanna B. Finnerup, Henriette Klit, Troels Staehelin Jensen. 2010. Central Pain Syndromes. , 267-278.
CrossRef32
Turo J. Nurmikko. 2010. Postherpetic Neuralgia. , 222-236.
CrossRef33
David A. Fishbain, Brandly Cole, John E. Lewis, Jinrun Gao. (2010) What Is the Evidence for Chronic Pain Being Etiologically Associated with the DSM-IV Category of Sleep Disorder Due to a General Medical Condition? A Structured Evidence-Based Review. Pain Medicine 11:2, 158-179
CrossRef34
Benjamin J. Wallisch. (2010) Anesthesia and analgesia for cancer-related amputation. Techniques in Regional Anesthesia and Pain Management 14:1, 25-31
CrossRef35
Diana D. Cardenas, Elizabeth R. Felix. (2009) Pain after Spinal Cord Injury: A Review of Classification, Treatment Approaches, and Treatment Assessment. PM&R 1:12, 1077-1090
CrossRef36
J. Maarrawi, L. Garcia-Larrea. (2009) Imagerie des réecepteurs opioїdes chez l’homme. Douleur et Analgésie 22:4, 248-260
CrossRef37
Rafael Galvez. (2009) Variable Use of Opioid Pharmacotherapy for Chronic Noncancer Pain in Europe: Causes and Consequences. Journal of Pain and Palliative Care Pharmacotherapy 23:4, 346-356
CrossRef38
Kevin T. White, Timothy R. Dillingham, Marlís González-Fernández, Linda Rothfield. (2009) Opiates for Chronic Nonmalignant Pain Syndromes. American Journal of Physical Medicine & Rehabilitation 88:12, 995-1001
CrossRef39
Giustino Varrassi, Chiara Angeletti, Cristiana Guetti, Franco Marinangeli, Antonella Paladini. (2009) Systemic opioid and chronic pain. European Journal of Pain Supplements 3:2, 77-83
CrossRef40
Antonio Martínez-Salio, Agustín Gómez De la Cámara, María Victoria Ribera Canudas, Jordi Montero Homs, Emilio Blanco Tarrío, Antonio Collado Cruz, Avelino Ferrero Méndez, Joan Molet Teixidó, Ángel Oteo-Álvaro, Rafael Gálvez Mateos, Enric Zamorano Bayarri, Andrés Peña Arrebola, Julio Pardo Fernández. (2009) Diagnóstico y tratamiento del dolor neuropático. Medicina Clínica 133:16, 629-636
CrossRef41
Jacqueline M. Leung, Laura P. Sands, Sudeshna Paul, Tim Joseph, Sakura Kinjo, Tiffany Tsai. (2009) Does Postoperative Delirium Limit the Use of Patient-controlled Analgesia in Older Surgical Patients?. Anesthesiology 111:3, 625-631
CrossRef42
Henriette Klit, Nanna B Finnerup, Troels S Jensen. (2009) Central post-stroke pain: clinical characteristics, pathophysiology, and management. The Lancet Neurology 8:9, 857-868
CrossRef43
Jack P. McNulty. (2009) Chronic Pain: Levorphanol, Methadone, and the N- Methyl-
d -Aspartate Receptor. Journal of Palliative Medicine 12:9, 765-766
CrossRef44
Richard L. Rauck, Mark S. Wallace, Allen W. Burton, Leonardo Kapural, James M. North. (2009) Intrathecal Ziconotide for Neuropathic Pain: A Review. Pain Practice 9:5, 327-337
CrossRef45
Andrew Zacest, Valerie C. Anderson, Kim J. Burchiel. (2009) The Glass Half Empty or Half Full-How Effective Are Long-Term Intrathecal Opioids in Post-herpetic Neuralgia? A Case Series and Review of the Literature. Neuromodulation: Technology at the Neural Interface 12:3, 219-223
CrossRef46
Bradley K. Taylor. (2009) Spinal inhibitory neurotransmission in neuropathic pain. Current Pain and Headache Reports 13:3, 208-214
CrossRef47
Jong S Kim. (2009) Post-stroke pain. Expert Review of Neurotherapeutics 9:5, 711-721
CrossRef48
Bishwanath Kumar, Jayantee Kalita, Gyanendra Kumar, Usha K. Misra. (2009) Central Poststroke Pain: A Review of Pathophysiology and Treatment. Anesthesia & Analgesia 108:5, 1645-1657
CrossRef49
Michael J. Brennan. (2009) Summary of Short-term and Long-term Oxymorphone Efficacy (Pain) Studies in Low Back Pain, Cancer Pain, Osteoarthritis, and Neuropathic Pain. Pain Medicine 10, S11-S19
CrossRef50
A. Van Zee. (2009) The Promotion and Marketing of OxyContin: Commercial Triumph, Public Health Tragedy. American Journal of Public Health 99:2, 221-227
CrossRef51
Don Gilden, Maria A Nagel, Ravi Mahalingam, Niklaus H Mueller, Elizabeth A Brazeau, Subbiah Pugazhenthi, Randall J Cohrs. (2009) Clinical and molecular aspects of varicella zoster virus infection. Future Neurology 4:1, 103-117
CrossRef52
Paul J. Christo, Chauncey T. Jones. 2009. COMPLEX REGIONAL PAIN SYNDROME: TREATMENT APPROACHES. , 284-294.
CrossRef53
Reena Halai, David J. Craik. (2009) Conotoxins: natural product drug leads. Natural Product Reports 26:4, 526
CrossRef54
Alec B. OʼConnor. (2009) Neuropathic Pain. PharmacoEconomics 27:2, 95-112
CrossRef55
Sumeet S. Panjabi, Ravi S. Panjabi, Marvin D. Shepherd, Kenneth A. Lawson, Michael Johnsrud, Jamie Barner. (2008) Extended-Release, Once-Daily Morphine (Avinza) for the Treatment of Chronic Nonmalignant Pain: Effect on Pain, Depressive Symptoms, and Cognition. Pain Medicine 9:8, 985-993
CrossRef56
Michael H. Levy, Marcin Chwistek, Rohtesh S. Mehta. (2008) Management of Chronic Pain in Cancer Survivors. The Cancer Journal 14:6, 401-409
CrossRef57
Peggy A. Compton, Stephen M. Wu, Beatrix Schieffer, Quynh Pham, Bruce D. Naliboff. (2008) Introduction of a Self-Report Version of the Prescription Drug Use Questionnaire and Relationship to Medication Agreement Noncompliance. Journal of Pain and Symptom Management 36:4, 383-395
CrossRef58
ED Kharasch, PS Bedynek, S Park, D Whittington, A Walker, C Hoffer. (2008) Mechanism of Ritonavir Changes in Methadone Pharmacokinetics and Pharmacodynamics: I. Evidence Against CYP3A Mediation of Methadone Clearance. Clinical Pharmacology & Therapeutics 84:4, 497-505
CrossRef59
Marie Besson, Valérie Piguet, Pierre Dayer, Jules Desmeules. (2008) New approaches to the pharmacotherapy of neuropathic pain. Expert Review of Clinical Pharmacology 1:5, 683-693
CrossRef60
Christopher L. Wu, Shefali Agarwal, Prabhav K. Tella, Brendan Klick, Michael R. Clark, Jennifer A. Haythornthwaite, Mitchell B. Max, Srinivasa N. Raja. (2008) Morphine versus Mexiletine for Treatment of Postamputation Pain. Anesthesiology 109:2, 289-296
CrossRef61
Joseph Pergolizzi, Rainer H Böger, Keith Budd, Albert Dahan, Serdar Erdine, Guy Hans, Hans-Georg Kress, Richard Langford, Rudolf Likar, Robert B. Raffa, Paola Sacerdote. (2008) Opioids and the Management of Chronic Severe Pain in the Elderly: Consensus Statement of an International Expert Panel with Focus on the Six Clinically Most Often Used World Health Organization step III Opioids (Buprenorphine, Fentanyl, Hydromorphone, Methadone, Morphine, Oxycodone). Pain Practice 8:4, 287-313
CrossRef62
Jane C. Ballantyne, Naomi S. Shin. (2008) Efficacy of Opioids for Chronic Pain. The Clinical Journal of Pain 24:6, 469-478
CrossRef63
Larry F. Chu, Martin S. Angst, David Clark. (2008) Opioid-induced Hyperalgesia in Humans. The Clinical Journal of Pain 24:6, 479-496
CrossRef64
Karin Lottrup Petersen, Thomas Meadoff, Scott Press, Michelle M. Peters, Matthew D. LeComte, Michael C. Rowbotham. (2008) Changes in morphine analgesia and side effects during daily subcutaneous administration in healthy volunteers. Pain 137:2, 395-404
CrossRef65
Christopher M Herndon, Rob W Hutchison, Hildegarde J Berdine, Zachary A Stacy, Judy T Chen, David D Farnsworth, Devra Dang, Joli D Fermo. (2008) Management of Chronic Nonmalignant Pain with Nonsteroidal Antiinflammatory Drugs. Pharmacotherapy 28:6, 788-805
CrossRef66
Christian Schinkel, Martin H. Kirschner. (2008) Status of immune mediators in complex regional pain syndrome type I. Current Pain and Headache Reports 12:3, 182-185
CrossRef67
J.H. Vranken, M.G.W. Dijkgraaf, M.R. Kruis, M.H. van der Vegt, M.W. Hollmann, M. Heesen. (2008) Pregabalin in patients with central neuropathic pain: A randomized, double-blind, placebo-controlled trial of a flexible-dose regimen. PAIN 136:1-2, 150-157
CrossRef68
David A. Fishbain, Brandly Cole, John Lewis, Hubert L. Rosomoff, R. Steele Rosomoff. (2008) What Percentage of Chronic Nonmalignant Pain Patients Exposed to Chronic Opioid Analgesic Therapy Develop Abuse/Addiction and/or Aberrant Drug-Related Behaviors? A Structured Evidence-Based Review. Pain Medicine 9:4, 444-459
CrossRef69
Tomasz R. Okon, Mathews Lal George. (2008) Fentanyl-Induced Neurotoxicity and Paradoxic Pain. Journal of Pain and Symptom Management 35:3, 327-333
CrossRef70
Robert H. Dworkin, Dennis C. Turk, Kathleen W. Wyrwich, Dorcas Beaton, Charles S. Cleeland, John T. Farrar, Jennifer A. Haythornthwaite, Mark P. Jensen, Robert D. Kerns, Deborah N. Ader, Nancy Brandenburg, Laurie B. Burke, David Cella, Julie Chandler, Penny Cowan, Rozalina Dimitrova, Raymond Dionne, Sharon Hertz, Alejandro R. Jadad, Nathaniel P. Katz, Henrik Kehlet, Lynn D. Kramer, Donald C. Manning, Cynthia McCormick, Michael P. McDermott, Henry J. McQuay, Sanjay Patel, Linda Porter, Steve Quessy, Bob A. Rappaport, Christine Rauschkolb, Dennis A. Revicki, Margaret Rothman, Kenneth E. Schmader, Brett R. Stacey, Joseph W. Stauffer, Thorsten von Stein, Richard E. White, James Witter, Stojan Zavisic. (2008) Interpreting the Clinical Importance of Treatment Outcomes in Chronic Pain Clinical Trials: IMMPACT Recommendations. The Journal of Pain 9:2, 105-121
CrossRef71
Guohua Zhang, Husam Mohammad, Brad D. Peper, Srinivasa Raja, Steven P. Wilson, Sarah M. Sweitzer. (2008) Enhanced Peripheral Analgesia Using Virally Mediated Gene Transfer of the μ-Opioid Receptor in Mice. Anesthesiology 108:2, 305-313
CrossRef72
Cathrine Baastrup, Nanna B Finnerup. (2008) Pharmacological Management of Neuropathic Pain Following Spinal Cord Injury. CNS Drugs 22:6, 455-475
CrossRef73
Francis V. Salinas, Khalid Malik, Honorio T. Benzon. 2008. Local Anesthetics for Regional Anesthesia and Pain Management. , 811-838.
CrossRef74
Christopher L. Wu, Elaina E. Liu, David N. Maine. 2008. Outcomes, Efficacy, and Complications of Neuropathic Pain. , 1249-1260.
CrossRef75
Perry G. Fine, David Casarett. 2008. Pain Management at the End of Life. , 1159-1177.
CrossRef76
Kayode A. Williams, Robert W. Hurley, Elaina E. Lin, Christopher L. Wu. 2008. Neuropathic Pain Syndromes. , 427-443.
CrossRef77
R. Likar, B. Krainer, R. Sittl. (2008) Challenging the equipotency calculation for transdermal buprenorphine: four case studies. International Journal of Clinical Practice 62:1, 152-156
CrossRef78
Jerome Schofferman, Daniel Mazanec. (2008) Evidence-informed management of chronic low back pain with opioid analgesics. The Spine Journal 8:1, 185-194
CrossRef79
Eric E. Prommer. (2007) Levorphanol Revisited. Journal of Palliative Medicine 10:6, 1228-1230
CrossRef80
Robert H. Dworkin, Alec B. O’Connor, Miroslav Backonja, John T. Farrar, Nanna B. Finnerup, Troels S. Jensen, Eija A. Kalso, John D. Loeser, Christine Miaskowski, Turo J. Nurmikko, Russell K. Portenoy, Andrew S.C. Rice, Brett R. Stacey, Rolf-Detlef Treede, Dennis C. Turk, Mark S. Wallace. (2007) Pharmacologic management of neuropathic pain: Evidence-based recommendations. PAIN 132:3, 237-251
CrossRef81
Giorgio Cruccu, Nadine Attal, Rod Taylor. 2007. Neuropathic Pain. , 47-58.
CrossRef82
Robert W Johnson, Gunnar Wasner, Patricia Saddier, Ralf Baron. (2007) Postherpetic neuralgia: epidemiology, pathophysiology and management. Expert Review of Neurotherapeutics 7:11, 1581-1595
CrossRef83
S Canavero, V Bonicalzi. (2007) Central pain syndrome: elucidation of genesis and treatment. Expert Review of Neurotherapeutics 7:11, 1485-1497
CrossRef84
Pedro Emilio Bermejo Velasco, Rocío Velasco Calvo. (2007) Nuevos fármacos antiepilépticos y dolor neuropático. De la medicina molecular a la clínica. Medicina Clínica 129:14, 542-550
CrossRef85
Nancy L. Wiedemer, Paul S. Harden, Isabelle O. Arndt, Rollin M. Gallagher. (2007) The Opioid Renewal Clinic: A Primary Care, Managed Approach to Opioid Therapy in Chronic Pain Patients at Risk for Substance Abuse. Pain Medicine 8:7, 573-584
CrossRef86
Shefali Agarwal, Michael Polydefkis, Brian Block, Jennifer Haythornthwaite, Srinivasa N. Raja. (2007) Transdermal Fentanyl Reduces Pain and Improves Functional Activity in Neuropathic Pain States. Pain Medicine 8:7, 554-562
CrossRef87
Amy M. Barrett, Melanie A. Lucero, Trong Le, Rebecca L. Robinson, Robert H. Dworkin, Amy S. Chappell. (2007) Epidemiology, Public Health Burden, and Treatment of Diabetic Peripheral Neuropathic Pain: A Review. Pain Medicine 8:s2 Duloxetine, S50-S62
CrossRef88
Jessica Robinson-Papp, David M. Simpson. (2007) Safety Profile of Treatment in Diabetic Peripheral Neuropathic Pain. Pain Medicine 8:s2 Duloxetine, S43-S49
CrossRef89
Claudia Vergelli, Maria Paola Giovannoni, Stefano Pieretti, Amalia Di Giannuario, Vittorio Dal Piaz, Pierfrancesco Biagini, Claudio Biancalani, Alessia Graziano, Nicoletta Cesari. (2007) 4-Amino-5-vinyl-3(2H)-pyridazinones and analogues as potent antinociceptive agents: Synthesis, SARs, and preliminary studies on the mechanism of action. Bioorganic & Medicinal Chemistry 15:16, 5563-5575
CrossRef90
Troels S Jensen, Nanna Brix Finnerup. (2007) Management of neuropathic pain. Current Opinion in Supportive and Palliative Care 1:2, 126-131
CrossRef91
Mugdha Gore, Alesia Sadosky, Kei-Sing Tai, Brett Stacey. (2007) A Retrospective Evaluation of the Use of Gabapentin and Pregabalin in Patients with Postherpetic Neuralgia in Usual-Care Settings. Clinical Therapeutics 29:8, 1655-1670
CrossRef92
Anjali Bhagra, Ravi D. Rao. (2007) Chemotherapy-induced neuropathy. Current Oncology Reports 9:4, 290-299
CrossRef93
Russell K. Portenoy, John T. Farrar, Misha-Miroslav Backonja, Charles S. Cleeland, Kaity Yang, Michael Friedman, Salvatore V. Colucci, Patricia Richards. (2007) Long-term Use of Controlled-release Oxycodone for Noncancer Pain: Results of a 3-year Registry Study. The Clinical Journal of Pain 23:4, 287-299
CrossRef94
David M. Simpson, John Messina, Fang Xie, Martin Hale. (2007) Fentanyl buccal tablet for the relief of breakthrough pain in opioid-tolerant adult patients with chronic neuropathic pain: a multicenter, randomized, double-blind, placebo-controlled study. Clinical Therapeutics 29:4, 588-601
CrossRef95
Jack P. McNulty. (2007) Can Levorphanol be Used Like Methadone for Intractable Refractory Pain?. Journal of Palliative Medicine 10:2, 293-296
CrossRef96
Michael Weaver, Sidney Schnoll. (2007) Addiction Issues in Prescribing Opioids for Chronic Nonmalignant Pain. Journal of Addiction Medicine 1:1, 2-10
CrossRef97
Hans Gustav Thyregod, Michael C. Rowbotham, Michelle Peters, Jessica Possehn, Marlene Berro, Karin Lottrup Petersen. (2007) Natural history of pain following herpes zoster. Pain 128:1-2, 148-156
CrossRef98
Eric Prommer. (2007) Levorphanol: the forgotten opioid. Supportive Care in Cancer 15:3, 259-264
CrossRef99
F. Parker, N. Aghakhani, N. Attal, S. Wolf. (2007) Malformazioni della cerniera craniocervicale e siringomielie. EMC - Neurologia 7:2, 1-16
CrossRef100
Miroslaw Backonja, Michael C. Rowbotham. 2007. Tratamiento farmacológico del dolor neuropático. , 1103-1111.
CrossRef101
Rollin M. Gallagher, Maripat Welz-Bosna, Arnold Gammaitoni. (2007) Assessment of Dosing Frequency of Sustained-Release Opioid Preparations in Patients with Chronic Nonmalignant Pain. Pain Medicine 8:1, 71-74
CrossRef102
Jörgen Boivie. 2007. Dolor central. , 1085-1102.
CrossRef103
Seema Mishra, Sushma Bhatnagar, Amit Kumar Singhal. (2007) High-dose Morphine for Intractable Phantom Limb Pain. The Clinical Journal of Pain 23:1, 99-101
CrossRef104
Paul J Christo, Greg Hobelmann, David N Maine. (2007) Post-Herpetic Neuralgia in Older Adults. Drugs & Aging 24:1, 1-19
CrossRef105
Joseph Maarrawi, Roland Peyron, Patrick Mertens, Nicolas Costes, Michel Magnin, Marc Sindou, Bernard Laurent, Luis Garcia-Larrea. (2007) Differential brain opioid receptor availability in central and peripheral neuropathic pain. Pain 127:1-2, 183-194
CrossRef106
JH Vranken, MH Vegt. (2006) De farmacologische behandeling van neuropathische pijn. Huisarts en Wetenschap 49:12, 874-882
CrossRef107
N. Attal, G. Cruccu, M. Haanpää, P. Hansson, T. S. Jensen, T. Nurmikko, C. Sampaio, S. Sindrup, P. Wiffen. (2006) EFNS guidelines on pharmacological treatment of neuropathic pain. European Journal of Neurology 13:11, 1153-1169
CrossRef108
Hsiang-En Wu, Han-Sen Sun, Caleb W. Cheng, Maia Terashvili, Leon F. Tseng. (2006) dextro-Naloxone or levo-naloxone reverses the attenuation of morphine antinociception induced by lipopolysaccharide in the mouse spinal cord via a non-opioid mechanism. European Journal of Neuroscience 24:9, 2575-2580
CrossRef109
Jane C. Ballantyne. (2006) Opioids for Chronic Nonterminal Pain. Southern Medical Journal 99:11, 1245-1255
CrossRef110
F. LOUIS. (2006) Transdermal buprenorphine in pain management - experiences from clinical practice: five case studies. International Journal of Clinical Practice 60:10, 1330-1334
CrossRef111
Miles J. Belgrade, Cassandra D. Schamber, Bruce R. Lindgren. (2006) The DIRE Score: Predicting Outcomes of Opioid Prescribing for Chronic Pain. The Journal of Pain 7:9, 671-681
CrossRef112
Vincenzo Bonicalzi, Sergio Canavero. (2006) Pharmacological treatment of neuropathic pain: present status and future directions. Therapy 3:5, 651-677
CrossRef113
Lauren Shaiova. (2006) Difficult Pain Syndromes. The Cancer Journal 12:5, 330-340
CrossRef114
Christopher L. Drake, Thomas Roth. (2006) Predisposition in the Evolution of Insomnia: Evidence, Potential Mechanisms, and Future Directions. Sleep Medicine Clinics 1:3, 333-349
CrossRef115
Pasquale Niscola, Laura Scaramucci, Claudio Romani, Marco Giovannini, Luca Maurillo, Giovanni Poeta, Claudio Cartoni, Edoardo Arcuri, Sergio Amadori, Paolo Fabritiis. (2006) Opioids in pain management of blood-related malignancies. Annals of Hematology 85:8, 489-501
CrossRef116
Elon Eisenberg, Ewan D McNicol, Daniel B Carr, Ewan D McNicol. 2006. Opioids for neuropathic pain. .
CrossRef117
Michael C. Rowbotham. (2006) Pharmacologic Management of Complex Regional Pain Syndrome. The Clinical Journal of Pain 22:5, 425-429
CrossRef118
Jean-Sébastien Walczak, Vincent Pichette, François Leblond, Karine Desbiens, Pierre Beaulieu. (2006) Characterization of chronic constriction of the saphenous nerve, a model of neuropathic pain in mice showing rapid molecular and electrophysiological changes. Journal of Neuroscience Research 83:7, 1310-1322
CrossRef119
J. Cavenagh, P. Good, P. Ravenscroft. (2006) Neuropathic pain: are we out of the woods yet?. Internal Medicine Journal 36:4, 251-255
CrossRef120
Montserrat Vera-Llonch, Ellen Dukes, Thomas E. Delea, Si-Tien Wang, Gerry Oster. (2006) Treatment of peripheral neuropathic pain: A simulation model. European Journal of Pain 10:3, 279-285
CrossRef121
David Niv, Marshall Devor. (2006) Refractory Neuropathic Pain: The Nature and Extent of the Problem. Pain Practice 6:1, 3-9
CrossRef122
Christian Schinkel, Andreas Gaertner, Johannes Zaspel, Siegfried Zedler, Eugen Faist, Matthias Schuermann. (2006) Inflammatory Mediators are Altered in the Acute Phase of Posttraumatic Complex Regional Pain Syndrome. The Clinical Journal of Pain 22:3, 235-239
CrossRef123
A. Frese, I.W. Husstedt, E.B. Ringelstein, S. Evers. (2006) Pharmacologic Treatment of Central Post-Stroke Pain. The Clinical Journal of Pain 22:3, 252-260
CrossRef124
Bruce Nicholson, Edgar Ross, Arnold Weil, John Sasaki, Gerald Sacks. (2006) Treatment of chronic moderate-to-severe non-malignant pain with polymer-coated extended-release morphine sulfate capsules. Current Medical Research and Opinion 22:3, 539-550
CrossRef125
Joseph R. Ineck, Ann M. Rule. (2006) Opioid Analgesics in the Substance Abuser. Journal of Pain and Palliative Care Pharmacotherapy 20:3, 39-41
CrossRef126
NANCY A. ALVAREZ, BRADLEY S. GALER, ARNOLD R. GAMMAITONI. 2006. Postherpetic Neuralgia in the Cancer Patient. , 123-137.
CrossRef127
Mellar P Davis. (2006) Management of Cancer Pain. American Journal of Cancer 5:3, 171-182
CrossRef128
Jane C. Ballantyne. (2006) Opioid Therapy. ASA Refresher Courses in Anesthesiology 34:1, 31-42
CrossRef129
David Niv, Alexander Maltsman-Tseikhin. (2005) Postherpetic Neuralgia: The Never-Ending Challenge. Pain Practice 5:4, 327-340
CrossRef130
Michael H. Ossipov, Frank Porreca. (2005) Challenges in the development of novel treatment strategies for neuropathic pain. NeuroRX 2:4, 650-661
CrossRef131
H WU, E SCHWASINGER, J HONG, L TSENG. (2005) Pretreatment with antiserum against dynorphin, substance P, or cholecystokinin enhances the morphine-produced anti-allodynia in the sciatic nerve ligated mice. Neuroscience Letters 386:1, 46-51
CrossRef132
Tatsuro Kohno, Ru-Rong Ji, Nobuko Ito, Andrew J. Allchorne, Katia Befort, Laurie A. Karchewski, Clifford J. Woolf. (2005) Peripheral axonal injury results in reduced μ opioid receptor pre- and post-synaptic action in the spinal cord. Pain 117:1-2, 77-87
CrossRef133
Helle Kirsten Erichsen, Jing-Xia Hao, Xiao-Jun Xu, Gordon Blackburn-Munro. (2005) Comparative actions of the opioid analgesics morphine, methadone and codeine in rat models of peripheral and central neuropathic pain. Pain 116:3, 347-358
CrossRef134
Chante Buntin-Mushock, Lisa Phillip, Kumi Moriyama, Pamela Pierce Palmer. (2005) Age-Dependent Opioid Escalation in Chronic Pain Patients. Anesthesia & Analgesia 100:6, 1740-1745
CrossRef135
Nathaniel Katz, Christine Benoit. (2005) Opioids for neuropathic pain. Current Pain and Headache Reports 9:3, 153-160
CrossRef136
Rudolf Likar, Reinhard Sittl. (2005) Transdermal Buprenorphine for Treating Nociceptive and Neuropathic Pain: Four Case Studies. Anesthesia & Analgesia 100:3, 781-785
CrossRef137
K. Henkel, D. Bengel. (2005) Gekreuztes zentral-neuropathisches Schmerzsyndrom nach bakterieller Meningoenzephalitis. Der Schmerz 19:1, 55-58
CrossRef138
Frank Birklein. (2005) Complex regional pain syndrome. Journal of Neurology 252:2, 131-138
CrossRef139
Kathleen Hempenstall, Turo J. Nurmikko, Robert W. Johnson, Roger P. A'Hern, Andrew S.C. Rice. (2005) Analgesic Therapy in Postherpetic Neuralgia: A Quantitative Systematic Review. PLoS Medicine 2:7, e164
CrossRef140
H. Chen, T. J. Lamer, R. H. Rho, K. A. Marshall, B. T. Sitzman, S. M. Ghazi, R. P. Brewer. (2004) Contemporary Management of Neuropathic Pain for the Primary Care Physician. Mayo Clinic Proceedings 79:12, 1533-1545
CrossRef141
Asokumar Buvanendran, Jeffrey S. Kroin, James M. Kerns, Subhash N. K. Nagalla, Kenneth J. Tuman. (2004) Characterization of a New Animal Model for Evaluation of Persistent Postthoracotomy Pain. Anesthesia & Analgesia1453-1460
CrossRef142
Marianne Kloke. (2004) Gaps and junctions between clinical experience and theoretical framework in the use of opioids. Supportive Care in Cancer 12:11, 749-751
CrossRef143
Michael H. Ossipov, Josephine Lai, Tamara King, Todd W. Vanderah, T. Philip Malan, Victor J. Hruby, Frank Porreca. (2004) Antinociceptive and nociceptive actions of opioids. Journal of Neurobiology 61:1, 126-148
CrossRef144
Charles E. Argoff, Nathaniel Katz, Miroslav Backonja. (2004) Treatment of postherpetic neuralgia: a review of therapeutic options. Journal of Pain and Symptom Management 28:4, 396-411
CrossRef145
A JONES. (2004) Cerebral decreases in opioid receptor binding in patients with central neuropathic pain measured by 611C9diprenorphine binding and PET. European Journal of Pain 8:5, 479-485
CrossRef146
Daniel Fischberg, R. Sean Forrison. (2004) Editor's Note. Journal of Palliative Medicine 7:4, 574-578
CrossRef147
Mike Namaka, Colin R. Gramlich, Dana Ruhlen, Maria Melanson, Ian Sutton, Joanne Major. (2004) A treatment algorithm for neuropathic pain. Clinical Therapeutics 26:7, 951-979
CrossRef148
Gil I. Wolfe, Jaya R. Trivedi. (2004) Painful peripheral neuropathy and its nonsurgical treatment. Muscle & Nerve 30:1, 3-19
CrossRef149
Gary McCleane. (2004) Pharmacological strategies in relieving neuropathic pain. Expert Opinion on Pharmacotherapy 5:6, 1299-1312
CrossRef150
Joan D. Penrod, R. Sean Morrison. (2004) Challenges for Palliative Care Research. Journal of Palliative Medicine 7:3, 398-402
CrossRef151
Eric Chevlen. (2004) Recent advances in clinical use of opioids. Current Pain and Headache Reports 8:3, 205-211
CrossRef152
Alexander FJE Vrancken, Ivo N van Schaik, Richard AC Hughes, Nicolette C Notermans, Alexander FJE Vrancken. 2004. Drug therapy for chronic idiopathic axonal polyneuropathy. .
CrossRef153
Heikki Mansikka, Chengshui Zhao, Rishi N. Sheth, Ichiro Sora, George Uhl, Srinivasa N. Raja. (2004) Nerve Injury Induces a Tonic Bilateral μ-Opioid Receptor–mediated Inhibitory Effect on Mechanical Allodynia in Mice. Anesthesiology 100:4, 912-921
CrossRef154
J SCHWARZ, N NAFF. (2004) The management of neuropathic pain. Neurosurgery Clinics of North America 15:2, 231-239
CrossRef155
Robert W Johnson, Tessa L Whitton. (2004) Management of herpes zoster (shingles) and postherpetic neuralgia. Expert Opinion on Pharmacotherapy 5:3, 551-559
CrossRef156
Misha-Miroslav Backonja, Jordi Serra. (2004) Pharmacologic Management Part 2: Lesser-Studied Neuropathic Pain Diseases. Pain Medicine 5:s1, S48-S59
CrossRef157
Mark W Douglas, Robert W Johnson, Anthony L Cunningham. (2004) Tolerability of Treatments for Postherpetic Neuralgia. Drug Safety 27:15, 1217-1233
CrossRef158
Pamela S Davies, Bradley S Galer. (2004) Review of Lidocaine Patch 5% Studies in the Treatment of Postherpetic Neuralgia. Drugs 64:9, 937-947
CrossRef159
D. Bouhassira, N. Attal, V. Tassain. (2004) Reply to Dr Walker's comments on Tassain et al. Long term effects of oral sustained release morphine on neuropsychological performance in patients with chronic non-cancer pain (Pain 2003;104:389–400). Pain 107:1-2, 192
CrossRef160
Ballantyne, Jane C., Mao, Jianren, . (2003) Opioid Therapy for Chronic Pain. New England Journal of Medicine 349:20, 1943-1953
Full Text161
Claudia Sommer. (2003) Painful neuropathies. Current Opinion in Neurology 16:5, 623-628
CrossRef162
Grewo Lim, Backil Sung, Ru-Rong Ji, Jianren Mao. (2003) Upregulation of spinal cannabinoid-1-receptors following nerve injury enhances the effects of Win 55,212-2 on neuropathic pain behaviors in rats. Pain 105:1-2, 275-283
CrossRef163
Douglas J. Weschules, Jill A. McMath, Rollin Gallagher, Calvin J. Alt, Calvin H. Knowlton. (2003) Methadone and the Hospice Patient: Prescribing Trends in the Home-Care Setting. Pain Medicine 4:3, 269-276
CrossRef164
(2003) Recent Literature. Journal of Palliative Medicine 6:4, 635-637
CrossRef165
(2003) Chronic Neuropathic Pain. New England Journal of Medicine 348:26, 2688-2689
Full Text166
Mendell, Jerry R., Sahenk, Zarife, . (2003) Painful Sensory Neuropathy. New England Journal of Medicine 348:13, 1243-1255
Full Text167
Foley, Kathleen M., . (2003) Opioids and Chronic Neuropathic Pain. New England Journal of Medicine 348:13, 1279-1281
Full Text168
Marco Pappagallo, E Joseph Haldey. (2003) Pharmacological Management of Postherpetic Neuralgia. CNS Drugs 17:11, 771-780
CrossRef
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