Marzia Lazzari

Palmitoylethanolamide in the Treatment of Chronic Pain Caused by Different Etiopathogenesis

OBJECTIVE To assess the efficacy and safety of palmitoylethanolamide (PEA), an endogenous fatty acid amide belonging to the N-acylethanolamines family, in reducing pain severity in patients with pain associated to different pathological conditions. METHODS This was an observational study conducted on 610 patients who were unable to effectively control chronic pain with standard therapies. PEA (600 mg) was administered twice daily for 3 weeks followed by single daily dosing for 4 weeks, in addition to standard analgesic therapies or as single therapy. The primary outcome measure was the mean score pain severity evaluated by the numeric rating scale. Safety was also evaluated. RESULTS PEA treatment significantly decreased the mean score pain intensity evaluated in all patients who completed the study. The PEA effect was independent of the pain associated pathological condition. PEA-induced decrease of pain intensity was present also in patients without concomitant analgesic therapy. Importantly, PEA showed no adverse effects. CONCLUSIONS In this study, PEA was effective and safe in the management of chronic pain in different pathological conditions.

Open questions in the treatment of cancer pain: time for a strong evidence-based approach?

Pain affects patients with cancer at any stage of their disease. Yet, it is not adequately treated in a significant percentage of cases. In 1986, the WHO proposed a three-step approach for the treatment of pain in cancer patients (from nonopioids to weak opioids to strong opioids, according to pain intensity) following the recommendations of an international group of experts. The application of the WHO strategy demonstrated that a clear and simple approach is of educational value and ensured worldwide dissemination. However, there is little evidence that the WHO approach is the best, and there are still several points to debate on the treatment of cancer pain.

Italian Oncological Pain Survey (IOPS) A Multicentre Italian Study of Breakthrough Pain Performed in Different Settings

Objective:A survey of breakthrough pain (BTP) was performed in five palliative care units (PCU), seven oncology departments (ONC), and nine pain clinics (OPC). Methods:A standard algorithm was used to confirm the diagnosis of BTP of patients refereed to different settings. Results:1,412 evaluable cancer patients were enrolled. 53.9% were males and the mean age was 63.7±13.1 years. The mean intensity of background pain was 2.8±0.73. Patients reported 2.4±1.1 BTP episodes/day with a mean intensity of 7.37±1.28. 80.6% patients reported that the BTP had a significant negative impact in everyday life. The majority of patients reported a fast onset of BTP, which was predictable in 50.7% of cases, while BTP with a gradual onset (>10 min) was less predictable (29%) (P=0.001). PCU patients were older, had lower Karnofsky levels, a lower number of BTP episodes/day, a slow onset of BTP onset, and a less predictable BTP. Cancer diagnosis was performed a mean of 23.5 months (SD±32.8) before the assessment. The mean duration of background pain was 3.5 months (SD±3.5), and the mean duration of any analgesic treatment was 2.5 months (SD±3). BTP started a mean of 2.2 months (SD±1.9) before the assessment. Characteristics of BTP were influenced by the course of disease, as well as the duration of background pain and initiation of BTP. Most patients took rapid onset opioids and were satisfied with the treatment. BTP diagnosis was prevalently made by ONC and OPC physicians, and rarely by GPs. Conclusion:This survey performed by an Italian observatory expert review group, has confirmed that the BTP represents a clinically relevant condition with a negative impact on the patient’s quality of life. BTP was detected in all settings involved. A number of factors are associated with the BTP. Also factors regarding the course of disease and setting of care have been assessed. This information may help in stratifying patients or predicting the risk of development of BTP with specific characteristics.

Prolonged-release oxycodone/naloxone in nonmalignant pain: Single-center study in patients with constipation

IntroductionOpioid treatment for chronic malignant and nonmalignant pain of moderateto-severe intensity is associated with bowel dysfunction leading to constipation; this often requires opioid dose reduction or interruption. Combination opioid agonist/antagonist therapy can restore normal bowel function. A prolonged-released (PR) fixed-dose combination of oxycodone and naloxone has been developed and efficacy has been demonstrated in phase 3 clinical trials.MethodsThis 2-month, retrospective, singlecenter, observational study assessed the effectiveness and safety of PR oxycodone/naloxone in consecutive nononcological patients with constipation and chronic pain despite analgesic treatment; specific subgroup analyses were performed in opioid-experienced or opioid-naïve patients and in age subgroups. Efficacy was assessed by: intensity of pain; bowel function; effective oxycodone/naloxone dose; Patients’ Global Impression of Change (PGIC) scale; rescue paracetamol; and laxative use. Safety evaluations were also performed.ResultsOf 1,051 patients starting on the oxycodone/naloxone combination (32.0% male; mean age 67 ± 13 years, 53.9% opioid naïve), 1,012 completed 2 months of treatment. Overall, PR oxycodone/naloxone was associated with a significant decrease in pain intensity (P < 0.001), a reduced need for rescue paracetamol (P < 0.001), and PGIC score of “very much improved” or “much improved” in 84.0% of patients. Constipation markedly decreased (P < 0.001) despite reduced laxative use (P < 0.001 vs. baseline). The most frequent treatment-emergent adverse events were somnolence (2.0%), dizziness (1.1%), and confusion (1.0%). Clinical differences in endpoints were seen between opioid-naïve and opioid-experienced patients, and among agestratified groups, but efficacy was similar to the overall population.ConclusionsFixed combination PR oxycodone/naloxone was effective and well tolerated in moderate-to-severe chronic pain in patients with constipation, providing analgesia and relief from bowel dysfunction. Consistent efficacy across patient subgroups provides guidance for daily management of chronic pain when therapy options are limited due to bowel dysfunction, regardless of age or previous medication. Supplementary material belonging to this paper is available on SpringerLink.

Preventing and managing herpes zoster: key actions to foster healthy aging

Population aging is the demographic phenomenon characterizing all countries in the world, and it is challenging the national infrastructures, in particular health systems. However, aging itself is not associated with increased medical spending, but disability and comorbidity that affect older individuals are the actual drivers for health expenditures. Therefore, if people age in better health, medical spending may be significantly reduced. Preventative interventions proved to be effective in reducing/preventing disease and disability and often found to be cost effective, include diet and exercise interventions, medications, routine disease screenings, and immunizations. Vaccination can protect older citizens against life-threatening diseases, such as influenza, pneumococcal infections, tetanus, and against diseases which adversely impact their quality of life, such as herpes zoster (HZ). Including HZ vaccination in its citizens’ lifetime immunization calendar can reinforce Europe’s commitment toward active, healthy aging. This paper outlines the consensus statement of a group of Italian experts on HZ.

Beyond the traditional definition of breakthrough pain: An observational study

IntroductionBreakthrough pain (BTP) is traditionally defined as a transitory pain flare in opioid-treated patients with chronic background pain. This definition has, however, been challenged in recent years. This study aimed to analyze BTP prevalence in different pain conditions.MethodsThis was a prospective, noninterventional, observational study conducted from June to September 2011 in two Italian pain treatment reference centres. Consecutive patients aged >18 years with oncological or non-oncological pain were eligible for this study; background pain was acute/ subacute (<3 months) or chronic (>3 months). The characteristics of pain were evaluated by means of a structured interview by physicians, and patients were asked to complete a dedicated clinical study form.The following outcomes were assessed: chronic pain duration (in patients with chronic pain), BTP prevalence, and number and severity of daily BTP episodes. All outcomes were assessed in four populations of patients with: (a) chronic oncological pain; (b) chronic non-oncological pain; (c) non-chronic oncological pain; (d) nonchronic non-oncological pain. The correlation between BTP and gender was also investigated.ResultsOf 1,270 patients with chronic pain, 1,086 had non-oncological pain (85.5%). Most patients (68.6%) with non-oncological pain were female (P = 0.001). Pain duration was significantly longer in non-oncological pain versus oncological pain groups (P = 0.002). BTP prevalence was lower in non-oncological patients (P < 0.001). No differences were reported in terms of number and severity of daily BTP episodes. BTP was more frequent in females with non-oncological pain (P = 0.04). Females had a significantly higher pain severity (P = 0.02) than males.ConclusionBTP is frequently reported in patients who do not have BTP according to the traditional definition. BTP frequency and severity is similar in oncological and non-oncological pain.

Effectiveness and tolerability of low-dose oral oxycodone/naloxone added to anticonvulsant therapy for noncancer neuropathic pain: an observational analysis.

Abstract Background: Opioids may alleviate chronic neuropathic pain (NP), but are considered second/third-line analgesia due to their poor gastrointestinal (GI) tolerability. A fixed combination of prolonged-release oxycodone and naloxone (OXN) has been developed to overcome the GI effects. The aim of this analysis was to evaluate analgesic effectiveness and tolerability of low-dose OXN in patients with moderate-to-severe noncancer NP despite analgesia. Methods: This retrospective observation of consecutive adult patients, treated open-label for 8 weeks at a single Italian centre, evaluated effectiveness (pain intensity numerical rating scale [NRS], Patients’ Global Impression of Change [PGIC], Douleur Neuropathique 4 inventory [DN4] and Chronic Pain Sleep Inventory [CPSI]), doses of daily OXN and adjuvant medication, rescue paracetamol use, bowel function index (BFI), laxative use, and safety. Results: Of 200 patients (mean age 65.9 years; 54% female) with NP included in the analysis; 97% completed 8 weeks’ treatment. At the observation start, all patients were taking anticonvulsants and complained of constipation, and 60% were receiving opioids. Pain intensity and DN4 score decreased significantly by endpoint (NRS p < 0.0001; DN4 p < 0.0001) and need for rescue analgesics abated. Reduction in pain intensity throughout the observation was similar regardless of NP aetiology. According to PGIC, 87.8% of patients were much/extremely improved, CPSI (p < 0.0001) and BFI were significantly improved (p < 0.0001) and laxative use decreased. No differences were found between patients <65 years vs those ≥65 years. OXN was generally well tolerated. Study limitations: Study limitations including the retrospective observational design, the lack of a control group and the single-centre design may limit the generalizability of our findings. Conclusions: Low-dose OXN (25.0 ± 12.5 mg/day) added to anticonvulsants was highly effective in controlling noncancer NP of varied aetiology, with reduced need for rescue analgesia and improved quality of sleep, and was well tolerated, with improved bowel function and reduced laxative use. The efficacy and tolerability of OXN demonstrated in this real-world setting suggest its utility in this difficult to manage patient population.

One-year follow-up of patients with long-lasting post-herpetic neuralgia

BackgroundRecent information on epidemiology and management of post-herpetic neuralgia (PHN), a painful complication of zoster, is scarce.MethodsThis study was conducted at the Pain Clinic of the Policlinico Tor Vergata, Rome, Italy, on eighty-five immunocompetent patients with a clinical diagnosis of PHN. At enrollment (time 0, T0), the patients were interviewed by physicians to obtain demographic data and information about their zoster clinical history and underwent a blood test for VZV-DNA research. DN4 and SF-12 questionnaires were used to assess the neuropathic nature of pain and the overall health status, respectively. A one-year follow-up was planned for enrolled cases, who were visited at regular intervals of at least 3 months.ResultsAt T0 all the patients were at least 6 months from the episode of acute zoster and still presented with intense pain (mean VAS =6.7; mean DN4 = 5.7). Using antivirals within 72 hours from the rash onset was associated to a significant reduction of pain at T0 (p = 0.006 vs untreated patients). Only 2.6% of patients treated with antivirals during acute zoster but 18.6% of the untreated ones presented with neuropathic pain at T12 (p =0.007), even though the two groups were similar at T0. VZV-DNA was found in 5 out of the 50 available blood samples. At the last follow-up visit, PCS and MCS scores of the PHN patients were found to be recovered over those of the historical age-matched healthy controls. Undesirable side effects of analgesic therapies were observed in 15.3 to 28.8% of the patients.ConclusionsPatients who six months after acute zoster still have significant neuropathic pain, have a high probability of suffering from chronic pain in the subsequent months/years. The initial antiviral treatment has a significant impact on the pain. Current strategies of analgesic therapy are effective to achieve relief of pain in PHN patients, but they are burdened with heavy and undesirable side effects.

Prevention of Herpes Zoster and its complications: From clinical evidence to real life experience

ABSTRACT Herpes zoster (HZ) is an acute viral illness characterized by a vesicular rash with unilateral distribution, which can also result in severe complications such as post-herpetic neuralgia (PHN), ophthalmic zoster, stroke or other neurological complications. The estimate incidence in Europe ranges between 2.0 and 4.6 cases per 1,000 person-years, with a sharp increase in >50 year-old subjects. Currently, treatment options for HZ are only partially effective in limiting the acute phase, while the management of complications is complex and often unsatisfactory. The total burden of the disease and the high costs related to its diagnostic and therapeutic management led researchers to develop a new preventive approach through a live attenuated virus vaccine. The currently available vaccine, with a high antigen content, is safe, well tolerated and reduces the incidence of HZ, PHN and the burden of illness. Several countries have introduced this vaccination, albeit with different recommendations and methods of financing. Taking into account the barriers to this immunization registered in some areas (difficulty of vaccine distribution, lack of physician recommendations, the cost of vaccine for patients, etc.), this group of Italian experts advocate that a common strategy able to guarantee a good compliance with this vaccination should be implemented. The same group addresses some practical questions concerning the use of zoster vaccine.

Reducing the burden of Herpes Zoster in Italy.

Herpes Zoster (HZ) is a viral disease with painful neuro-dermatologic manifestations. Incidence increases with age. In Italy, the estimated incidence is 6.3 cases/1000 person/year; hospital admissions are less than 2%, 69% in patients aged over 65 years. The most frequent complication of HZ is Post-Herpetic Neuralgia (PHN) characterized by metameric pain, allodynia, and hyperalgesia. In Italy 20.6% and 9.2% of HZ patients experience PHN after 3 and 6 months, respectively. Available antiviral and analgesic treatments are relatively unsatisfactory in reducing pain and length of the disease. Prevention has recently become possible with the live attenuated vaccine Oka/Merck. Clinical studies show a reduction of 51% in the incidence of the disease, 61% of its burden and 67% of PHN in vaccinees. Protection seems to be long lasting and vaccine safety matches registration requirements. Available evidence suggests that the costs for QALY (less than € 20 000) and avoided cases is favorable. Due to the heavy burden of disease, it is time to offer this vaccination to elderly population.Herpes Zoster (HZ) is a viral disease with painful neuro-dermatologic manifestations. Incidence increases with age. In Italy, the estimated incidence is 6.3 cases/1000 person/year; hospital admissions are less than 2%, 69% in patients aged over 65 years. The most frequent complication of HZ is Post-Herpetic Neuralgia (PHN) characterized by metameric pain, allodynia, and hyperalgesia. In Italy 20.6% and 9.2% of HZ patients experience PHN after 3 and 6 months, respectively. Available antiviral and analgesic treatments are relatively unsatisfactory in reducing pain and length of the disease. Prevention has recently become possible with the live attenuated vaccine Oka/Merck. Clinical studies show a reduction of 51% in the incidence of the disease, 61% of its burden and 67% of PHN in vaccinees. Protection seems to be long lasting and vaccine safety matches registration requirements. Available evidence suggests that the costs for QALY (less than € 20 000) and avoided cases is favorable. Due to the heavy burden of disease, it is time to offer this vaccination to elderly population.