Intraepidermal nerve fibre density in cancer patients receiving adjuvant chemotherapy.

BACKGROUND: Chemotherapy-induced neuropathy is a common adverse event in patients receiving vinca alcaloids, platinum derivatives and taxanes. However, the underlying pathogenetic mechanisms have not been completely elucidated. We set up a prospective pilot study on skin biopsies in newly diagnosed cancer patients receiving neurotoxic chemotherapeutic agents as adjuvant treatment in order to study the occurrence of small-fibre pathology and its relationship to clinical symptoms. PATIENTS AND METHODS: Skin biopsies from distal leg were performed in 12 patients before, during and after chemotherapy. Using light microscopy, the intraepidermal nerve fibre (IENF) density was determined from the skin biopsies by counting morphometrically the immunopositive nerves per epidermal area. RESULTS: Reduced IENF density was observed in eight patients at baseline. During the follow-up, the IENF density increased significantly in six patients and remained unchanged in two. In four patients, the IENF density was normal both at baseline and at the end of the follow-up period. Neuropathic symptoms were manifested in nine patients, but no association with the IENF count was found. CONCLUSION: During chemotherapy, results from patients revealed different evolutionary patterns of IENF density, but symptoms and IENF density were not related.

Treatment considerations for patients with neuropathic pain and other medical comorbidities.

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.

Treatment considerations for elderly and frail patients with neuropathic pain.

Currently, an estimated 38 million individuals 65 years or older live in the United States, and more than 11 million of these individuals are 80 years or older. Older people are at high risk of neuropathic pain because many diseases that cause neuropathic pain increase in incidence with age. Depending on their underlying health, older adults with neuropathic pain may have to cope with multiple coexisting diseases, polypharmacy, and impaired functional ability. The objective of this article is to review how aging and frailty affect the treatment of older adults with neuropathic pain. Specific topics reviewed include the complexity of treatment decisions in older patients due to aged heterogeneity, multimorbidity, and polypharmacy; selection of treatment in an effort to maximize patients' functional abilities in addition to relieving their pain; more careful dosing (usually lower) and monitoring of pharmacotherapy relative to younger patients due to age-related changes in pharmacokinetics and pharmacodynamics; and underrepresentation of older adults in clinical trials of neuropathic pain treatments, which further compromises physicians' ability to make informed treatment decisions.

Recommendations for the pharmacological management of neuropathic pain: an overview and literature update.

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 alpha(2)-delta 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.

Assessment of neuropathic pain in primary care.

Management of patients presenting with chronic pain is a common problem in primary care. Essentially, the classification of chronic pain falls into 3 broad categories: (1) pain owing to tissue disease or damage (nociceptive pain), (2) pain caused by somatosensory system disease or damage (neuropathic pain), and (3) pain without a known somatic background. Key challenges in developing a targeted holistic approach to treatment include appropriate diagnosis of the cause or causes of pain; identifying the type of pain and assessing the relative importance of its various components; and determining appropriate treatment. In clinical examination, sensory abnormalities are the crucial findings leading to a diagnosis of neuropathic pain, for which pharmacotherapy with antidepressants and anticonvulsants represents the cornerstone of medical treatment. Chronic neuropathic pain is underrecognized and undertreated, yet primary care physicians are uniquely placed on the frontlines of patient management, where they can play a pivotal role in treatment and prevention through diagnosis, therapy, follow-up, and referral. This review provides guidance in understanding and identifying the neuropathic contribution to pain presenting in primary care; assessing its severity through patient history, physical examination, and appropriate diagnostic tests; and establishing a rational treatment plan.

Recommendations for the management of herpes zoster.

The objective of this article is to provide evidence-based recommendations for the management of patients with herpes zoster (HZ) that take into account clinical efficacy, adverse effects, impact on quality of life, and costs of treatment. Systematic literature reviews, published randomized clinical trials, existing guidelines, and the authors' clinical and research experience relevant to the management of patients with HZ were reviewed at a consensus meeting. The results of controlled trials and the clinical experience of the authors support the use of acyclovir, brivudin (where available), famciclovir, and valacyclovir as first-line antiviral therapy for the treatment of patients with HZ. Specific recommendations for the use of these medications are provided. In addition, suggestions are made for treatments that, when used in combination with antiviral therapy, may further reduce pain and other complications of HZ.

Electroconvulsive therapy in patients with depression and fibromyalgia.

The effect of electroconvulsive therapy (ECT) on depression and other symptoms of fibromyalgia was studied in a prospective 3-month trial in 13 patients with fibromyalgia and concomitant depression. All the patients met the DSM-IV diagnostic criteria for Major Depressive Disorder and fulfilled the American College of Rheumatology diagnostic criteria for fibromyalgia. The Montgomery and Asberg Depression Rating Scale (MADRS) and the clinical global impression scale (CGI) were used to assess the severity of depression and the clinical change of the patients. The fibromyalgia impact questionnaire (FIQ) was used to evaluate the severity of the fibromyalgia symptoms. The intensity of pain was evaluated using a 6-point scale (0=no pain, 5=very severe pain), and tender point palpation. All assessments were performed at baseline and at follow-up visits, which took place one week, one month and three months after ECT. There was a significant improvement in depression after ECT according to MADRS. Using CGI, six patients were much or very much improved, while four patients were minimally improved and three patients had no change. There was significant improvement in four out of ten FIQ item scores, "feel good", "fatigue", "anxiety" and "depression". No significant change was found in the FIQ item scores "physical function", "pain", "stiffness" and "morning tiredness" or number of tender points and self-reported pain. We conclude that ECT is a safe and effective treatment for depression in fibromyalgia patients, but has no effect on the pain or other physical symptoms of these patients.