Pain as a First Manifestation of Paraneoplastic Neuropathies: A Systematic Review and Meta-Analysis.

INTRODUCTION: Paraneoplastic neurological syndromes (PNS) consist of a heterogeneous group of neurological disorders triggered by cancer. The aim of this systematic review is to estimate the reported prevalence of pain in patients with paraneoplastic peripheral neuropathy (PPN). METHODS: A systematic computer-based literature search was conducted on PubMed database. RESULTS: Our search strategy resulted in the identification of 126 articles. After the eligibility assessment, 45 papers met the inclusion criteria. Full clinical and neurophysiological data were further extracted and involved 92 patients with PPN (54.5% males, mean age 60.0 ± 12.2 years). The commonest first manifestation of PPN is sensory loss (67.4%), followed by pain (41.3%), weakness (22.8%), and sensory ataxia (20.7%). In 13.0% of the cases, pain was the sole first manifestation of the PPN. During the course of the PPN, 57.6% of the patients may experience pain secondary to the neuropathy. CONCLUSIONS: Pain is very prevalent within PPN. Pain specialists should be aware of this. Detailed history-taking, full clinical examination, and requesting nerve conduction studies might lead to an earlier diagnosis of an underlying malignancy

Pain in platin-induced neuropathies: A systematic review and meta-analysis

INTRODUCTION: Platin-induced peripheral neuropathy (PIPN) is a common cause of PN in cancer patients. The aim of this paper is to systematically review the current literature regarding PIPN, with a particular focus on epidemiological and clinical characteristics of painful PIPN, and to discuss relevant management strategies. METHODS: A systematic computer-based literature search was conducted on the PubMed database. RESULTS: This search strategy resulted in the identification of 353 articles. After the eligibility assessment, 282 articles were excluded. An additional 24 papers were identified by scanning the reference lists. In total, 95 papers met the inclusion criteria and were used for this review. The prevalence of neuropathic symptoms due to acute toxicity of oxaliplatin was estimated at 84.6%, whereas PN established after chemotherapy with platins was estimated at 74.9%. Specifically regarding pain, the reported prevalence of pain due to acute toxicity of oxaliplatin was estimated at 55.6%, whereas the reported prevalence of chronic peripheral neuropathic pain in PIPN was estimated at 49.2%. CONCLUSION: Peripheral neuropathy is a common complication in patients receiving platins and can be particularly painful. There is significant heterogeneity among studies regarding the method for diagnosing peripheral neuropathy. Nerve conduction studies are the gold standard and should be performed in patients receiving platins and complaining of neuropathic symptoms post-treatment

A meta-analysis to determine the effect of pharmacological and non-pharmacological treatments on fibromyalgia symptoms comprising OMERACT-10 response criteria

Fibromyalgia is characterized by widespread pain, sleep problems, fatigue, functional impairment, psychological distress, and cognitive dysfunction. The objective of this meta-analysis is to synthesize the available data on the effectiveness of pharmacological and non-pharmacological interventions across all domains included in the Outcome Measures in Rheumatology Clinical Trials (OMERACT-10) fibromyalgia response definitions, and to examine response based on these definitions. We searched Cochrane, PubMed, Scopus, and the reference lists of articles for randomized controlled trials of any drug formulation or non-pharmacological intervention used for fibromyalgia treatment. We extracted efficacy data regarding pain, sleep, physical function, fatigue, anxiety, depression, and cognition. The available data were insufficient to draw definite conclusions regarding response. Indirect evidence indicates that it may be expected with the use of serotonin noradrenaline reuptake inhibitors (SNRIs), noradrenaline reuptake inhibitors (NRIs), and multidisciplinary treatment. © 2015, International League of Associations for Rheumatology (ILAR)

Cancer pain relief by epidural PCA pump infusion through tunneled epidural catheters

Introduction. Seventy to eighty percent of terminally -ill cancer patients will experience moderate to severe pain at some stage of their illness. At present most of these will die in pain. The main reasons for failure to achieve control of this pain are inexperience and lack of knowledge of the simple principles of effective analgesic use, and in many countries the non-availability of strong opioid analgesics. Most of us accept that administering opioids orally is the best route because of simplicity and cost effectiveness. However, elementary gastrointestinal dysfunction is an indication that alternative routes of drug administration must be used. Subcutaneous, intraspinal, transdermal and transmucosal administrations are some of the more widely - accepted alternative routes. Spinal analgesia by epidural or intrathecal analgesic infusion has become a valuable tool in the treatment of cancer pain. We report here our results of 10 years experience in pain relief and palliative care at the university of Athens, using epidural PCA pump infusion through tunneled epidural catheters. Methods. One hundred and seventy - four patients with different kinds of abdominal cancer all experiencing from average to extreme pain were selected for pain relief with EPCA, using tunneled epidural catheters. The study took place after the approval of the University's Ethics Committee. All the patients had a routine epidural procedure using a standard nylon Portex epidural catheter 16 G that was tunneled subcutaneously and externalized in the umbilicus area. All also had a portable Pharmacia PCA pump. Micropore filters were employed in all cases and changed every five days. The analgesic mixture of preference was morphine, bupivacaine 0,5% and clonidine. The dose chosen to start the infusion depended on the previous dose of the oral morphine. The mean dose of initial morphine was 1.5-5 and the maximum dose 4.5 - 80mg/24h. For bupivacaine this was 60 - 70mg and for clonidine 75 - 600ug daily. The average number of catheter days per patient was 80.2 (2-875 days). All th'j patients were asked to answer the question whether the relief of pain and the patient's quality of life are synonymous. The VAS, the complications, the side-effects and the quality of life were assessed. Results Our results showed first that while the pain level before implanting the epidural catheter was 8-10 (x =8.8) the pain level following EPCA was 1-3 ( x =2.2). Secondly, regarding complications, only one patient (0.64%) suffered from epidural abscess and 8 patients (5.19%) experienced some form of infection in the catheter insertion site. This infection was treated successfully with antibiotics. Moreover, only 4 of the 154 catheters became occluded. The major side-effect was constipation in 32 patients (21.8%, while 22 patients (12.6%) suffered from nausea and vomiting. None of our patients showed respiratory depression. 90,8% of our patients answered that their quality of life depended completely on their pain relief. The rest answered that nursing care, psychological support and family support were as equally important as pain relief. Discussion The results suggest that EPCA pump infusion can offer good analgesia and an improved quality of life for terminally - ill cancer patients. We believe that further advances in producing drug delivery systems that are less invasive, more versa life and expensive will lead to the wider use of the PCA system

Pregabalin vs. Opioids for the treatment of neuropathic cancer pain: A prospective, head-to-head, randomized, open-label study

Objectives: Neuropathic cancer pain (NCP) is a common manifestation of cancer and/or its treatment. Treatment following the WHO analgesic ladder provides relief for the majority of cancer pain patients; however, concern remains that opioids may be less efficacious for neuropathic pain (NP) compared with nociceptive pain, often necessitating the use of higher doses. Adjuvants, such as pregabalin, have shown to be efficacious for the treatment of NP, although data come mostly from noncancer studies. The comparative efficacy and safety of opioids versus adjuvants has not been studied for NCP. The aim of this study was to directly compare pregabalin versus a strong opioid for the treatment of NCP. Methods: A total of 120 patients, diagnosed with "definite" NCP, were randomized into two groups and received increasing doses of either oral pregabalin or transdermal fentanyl for 28 days. VAS score, patient satisfaction, need for opioid rescue, and adverse events (AEs) were recorded. Results: In the pregabalin group, a significantly higher proportion of patients achieved at least 30% reduction in VAS compared with the fentanyl group (73.3%, 95% CI: 60.3%-83.93 vs. 36.7%, 95% CI: 24.5%-50.1%, P < 0.0001, respectively), while the percentage mean change from baseline was also significantly different [46% (95% CI: 39.5%-52.8%) for pregabalin and 22% (95% CI: 14.9%-29.5%) for fentanyl (P < 0.0001)]. Patient-reported satisfaction was more frequent with pregabalin, while AEs and treatment discontinuations were more frequent in the fentanyl group. Discussion: Prompt use of a neuropathic pain-specific adjuvant, such as pregabalin, in NCP may lead to better control of the neuropathic component, with opioid-sparing effects. © 2013 World Institute of Pain

Therapeutic management of chronic neuropathic pain: An examination of pharmacologic treatment

Neuropathic pain is defined as pain caused by a lesion in the nervous system and is common in clinical practice. Diagnosis can be difficult. Recommendations for first-line pharmacologic treatments are based on positive results from multiple, randomized, controlled trials, and recommendations for second-line pharmacologic treatments are based on the positive result of a single, randomized, controlled trial or inconsistent results of multiple, randomized, controlled trials. The results of published trials and clinical experience provide the foundation for specific recommendations for first-line treatments, which include gabapentin, 5% lidocaine patch, opioid analgesics, tramadol hydrochloride, and tricyclic antidepressants (TCAs). Gabapentin (up to 3,600 mg/day) significantly reduced pain compared with placebo; improvements in sleep, mood, and quality of life were also demonstrated. Adverse effects of gababentin include somnolence and dizziness, and, less commonly, gastrointestinal symptoms and mild peripheral edema. Thus, monitoring and dosage adjustment are required, without discontinuation of the drug. Gabapentin combined with morphine achieved better analgesia at lower doses of each drug than each drug alone, with only mild adverse effects. The first medication that proved effective for neuropathic pain in placebo-controlled trials was TCAs. Treatment decisions for patients with neuropathic pain can be difficult. Interest in the mechanisms and treatment of chronic neuropathic pain has increased during the past years, resulting in significant treatment advances in the future. In this article all recent knowledge on therapeutic management of chronic neuropathic pain is presented. © 2006 New York Academy of Sciences