The Neuropathic Pain Special Interest Group of the International Association for the Study of Pain recently sponsored the development of evidence-based guidelines for the pharmacological treatment of neuropathic pain. Tricyclic antidepressants, dual reuptake inhibitors of serotonin and norepinephrine, calcium channel a 2 -d ligands (ie, gabapentin and pregabalin), and topical lidocaine were recommended as first-line treatment options on the basis of the results of randomized clinical trials. Opioid analgesics and tramadol were recommended as second-line treatments that can be considered for first-line use in certain clinical circumstances. Results of several recent clinical trials have become available since the development of these guidelines. These studies have examined botulinum toxin, high-concentration capsaicin patch, lacosamide, selective serotonin reuptake inhibitors, and combination therapies in various neuropathic pain conditions. The increasing number of negative clinical trials of pharmacological treatments for neuropathic pain and ambiguities in the interpretation of these negative trials must also be considered in developing treatment guidelines. The objectives of the current article are to review the Neuropathic Pain Special Interest Group guidelines for the pharmacological management of neuropathic pain and to provide a brief overview of these recent studies.Mayo Clin Proc. 2010;85(3)(suppl):S3-S14 DPN = diabetic peripheral neuropathy; HIV = human immunodeficiency virus; HRQoL = health-related quality of life; NeuPSIG = Neuropathic Pain Special Interest Group; NP = neuropathic pain; PHN = postherpetic neuralgia; RCT = randomized clinical trial; SSNRI = selective serotonin norepinephrine reuptake inhibitor; SSRI = selective serotonin reuptake inhibitor; TCA = tricyclic antidepressant

No abstract

No abstract

No abstract

No abstract

No abstract

Eighteen patients suffering from cancer were entered into a study of the pharmacokinetics and efficacy of methadone and morphine in pain control. All patients had both clinical and radiological evidence of metastatic spread of their cancer and there were no significant differences in age, weight and sites of the primary cancer between the methadone (n = 9) and morphine (n = 9) groups. Blood opioid concentration, visual analogue pain scores (VAPS) and end-tidal percent carbon dioxide were measured before and after both an intravenous and oral dose of either methadone or morphine. Terminal half-lives (mean +/- S.D.) were 30.4 +/- 16.3 h and 2.7 +/- 1.2 h respectively for methadone and morphine while the clearance values (mean +/- S.D.) were 0.19 +/- 0.13 l/min and 1.16 +/- 0.47 l/min. The long half-life of methadone was associated with prolonged pain relief. However, the large variation in the half-life of methadone necessitated careful adjustment of the dosing interval in individual patients. There were pronounced differences in oral bioavailability between the two opioids: methadone, 79 +/- 11.7%, compared to morphine, 26 +/- 13% (mean +/- S.D.). Of greater clinical significance was the variability in these bioavailability estimates with a coefficient of variation of 15% for methadone compared to 50% for morphine. The combined effects of low and variable oral bioavailability for morphine may result in sub-therapeutic doses being administered as practitioners may be inhibited by the size of the effective oral morphine dose and may be confused by the variability in this dose compared to intramuscular doses. The initial oral dose of morphine varied from 15 mg 4 hourly to 150 mg 3 hourly, while the initial dose for methadone varied from 15 mg on alternate nights to 20 mg twice daily. There was no rapid escalation of daily opioid dose for either methadone or morphine when adequate pain control was provided rapidly at the start of treatment by the technique described in this study.

The efficacy of drugs for neuropathic pain has been established in randomized controlled trials that have excluded patients with comorbid conditions and those taking complex medications. However, patients with neuropathic pain frequently present with complex histories, making direct application of this evidence problematic. Treatment of neuropathic pain needs to be individualized according to the cause of the pain, concomitant diseases, medications, and other individual factors. Tricyclic antidepressants (TCAs), gabapentinoids, selective noradrenergic reuptake inhibitors, and topical lidocaine are the first-line choices; if needed, combination therapy may be used. When a new drug is added, screening for potential drug interactions is recommended. The TCAs have anticholinergic adverse effects and may cause orthostatic hypotension. They should be avoided or used cautiously in patients with cardiac conduction disturbances or arrhythmias. Patients who lack cytochrome P450 2D6 isoenzyme activity are prone to adverse effects of TCAs and venlafaxine and have a weaker analgesic response to tramadol. A combination of several serotoninergic drugs may lead to serotonin syndrome. Risk of gastrointestinal tract bleeding is increased in patients taking selective serotonin reuptake inhibitors or venlafaxine, especially when combined with nonsteroidal anti-inflammatory drugs. Dose adjustment may be needed in patients with renal or hepatic impairment. Depending on the drug, the dose is reduced or the dosage interval lengthened. Slow titration and careful follow-up are needed. No drug is absolutely safe during pregnancy and lactation. Particular care must be exercised during the first trimester when drug dose should be as low as possible. Individual weighing of benefits and risks should guide therapeutic decisions.Mayo Clin Proc. 2010;85(3)(suppl):S15-S25 ADR = adverse drug reaction; BP = blood pressure; CKD = chronic kidney disease; CYP = cytochrome P450; ECG = electrocardiogram; EM = extensive metabolizer; GFR = glomerular filtration rate; MI = myocardial infarction; NP = neuropathic pain; NSAID = nonsteroidal anti-inflammatory drug; OR = odds ratio; PM = poor metabolizer; RCT = randomized controlled trial; SNRI = selective noradrenergic reuptake inhibitor; TCA = tricyclic antidepressant; UM = ultrarapid metabolizer From Rehabilitation ORTON,