Feasibility of therapeutic music listening in fibromyalgia: a randomised controlled pilot study.

BACKGROUND: Fibromyalgia patients can benefit from music approaches as complementary treatments. In the literature, it was shown that these interventions managed pain conditions as well as reduced complaints, increased relaxation, and improved moods. OBJECTIVE: This study aimed at evaluating music therapy, in the form of therapeutic music listening, specifically for patients with fibromyalgia, to treat chronic pain by reducing pain perception, increasing well-being, and improving quality of life. METHODS: Twenty-four patients with fibromyalgia were recruited to take part in this feasibility pilot study that adopted a between-subject and within-subject design. Participants were randomised into three groups: (1) standard care, (2) standard care plus preferred music listening, (3) standard care plus Melomics-Health music listening, composed by an algorithm. Participants in experimental groups listened to 30 min of music at home, twice a day for a month. Patients' perceptions of changes following the listening, the intensity of pain and its interference in their lives, physical and mental well-being, and reported attitudes towards listening to music were evaluated respectively through the patients' global impression of change, the brief pain inventory, the Short Form Healthy Survey-12, and the cognitive behavioural assessment-outcome evaluation. RESULTS: The study showed that music listening can significantly affect mental well-being compared to no music. Moreover, the effects in the Melomics-Health group are maintained at follow-up. No significant effect on pain perception was noted. CONCLUSIONS: The study provides information supporting a possible role of music listening in improving well-being of patients with fibromyalgia.

Management of Osteoarthritis: Expert Opinion on NSAIDs.

Osteoarthritis (OA) is a leading cause of disability among older adults worldwide. Treatment aims are to alleviate inflammatory pain and improve physical function through non-pharmacological and pharmacological interventions. Non-steroidal anti-inflammatory drugs (NSAIDs) are recommended as first-line therapy. However, selection is challenged by patient age, comorbidities and polypharmacy, and by the drug's benefit/risk balance, all of which together influence the risk of cardiovascular (CV), gastrointestinal (GI) and renal adverse events (AEs). While the efficacy profile of the various NSAIDs is delineated, the differences in their safety profile are not straightforward. This narrative review provides practical indications by a multidisciplinary Italian expert panel for general practitioners and specialists managing OA patients with chronic inflammatory pain; the goal is to maximize therapy efficacy while reducing untoward effects caused by inappropriate NSAID use. The discussion on the best approach to NSAIDs spanned the following topics: (1) patient evaluation: investigate pain origin, duration and components together with possible risk factors for CV, GI and renal AEs; (2) non-pharmacological interventions: the physiatrist provides a person-centered, holistic approach accounting for all patient aspects; (3) pharmacological interventions: patient profile and drugs' pharmacological properties affect NSAID selection, which drugs to be used in combination or to be avoided, formulation and therapy duration; (4) the pharmacologist's, general practitioner's and pain therapist's points of view; (5) NSAID safety: the individual baseline risk and the drug's safety profile are major determinants of CV, GI and renal risk; consider possible drug-drug interactions; (6) periodical re-evaluation of treatment response and adherence, using scales to assess pain and function.

Not All Pain is Created Equal: Basic Definitions and Diagnostic Work-Up.

Chronic pain is considered a public health priority by the World Health Organization and European health institutions. It has reached alarming proportions in terms of disability, consumption of health and social resources, and impact on primary and specialist care services. Primary care physicians are often called on to manage this condition. Chronic pain management can be challenging due to its complexity. It has traditionally been considered to include nociceptive pain that that persists longer than the normal healing time, neuropathic pain lasting more than 3 months, or a combination of these. More recently, a third descriptor, nociplastic (primary) pain, was added to classify patients with chronic pain conditions such as fibromyalgia, nonspecific back pain, or mixed pain that persists or other conditions in which altered central pain modulation results in central sensitization and chronic pain in the absence of actual or threatened damage to tissues, including in the somatosensory nervous system. This document provides an overview of pain types and their underlying mechanisms. Successful pain management is facilitated by identification of the pain type. A set of diagnostic tools and a pain algorithm are presented to guide the clinician toward the correct diagnosis. The algorithm identifies cases that may require referral to a pain specialist. Once the site of origin of the pain (the "pain generator") is identified, or a primary pain syndrome is suspected, the accompanying article provides information and rationale to support treatment decisions based on patient characteristics.

Pharmacological Management of Adults with Chronic Non-Cancer Pain in General Practice.

Chronic pain is a public health priority that affects about 20% of the general population, causing disability and impacting productivity and quality of life. It is often managed in the primary care setting. Chronic pain management is most effective when the pain mechanism has been identified and addressed by appropriate therapy. This document provides an overview of pharmacological therapy for chronic non-cancer pain in the primary care setting, with the aim of improving treatment decisions based on the underlying pain mechanisms and pain neuroscience.

Pain diagnosis and treatment according to the pain generating factors.

SUMMARY: Chronic pain impacts on many aspects of patient life affecting autonomy, sleep, social activities and also employment. Adequate pain control is often challenging in patients with chronic pain, despite the availability of many medications and interventional techniques. Limitations to successful pain treatment are the poor understanding of contributing mechanisms and the lack of a mechanism based approach in clinical practice. The purpose of this article is to identify the factors contributing to pain generation in order to guide a personalized treatment. We analyze tissue specificity for chemical and physical stresses potentially causing pain, the changes that occur in the peripheral and central pain pathways during disease, the stimuli that, acting on a pathological pain pathway, can trigger pain. The pain generating factors should be recognized in each patient and addressed with pharmacological, rehabilitation and invasive interventions.

Capsaicin 8% dermal patch in clinical practice: an expert opinion.

INTRODUCTION: Neuropathic pain (NP) is caused by a lesion or disease of the somatosensory system, which can severely impact patients' quality of life. The current-approved treatments for NP comprise of both centrally acting agents and topical drugs, including capsaicin 8% dermal patches, which is approved for the treatment of peripheral NP. AREAS COVERED: The authors summarize literature data regarding capsaicin use in patients who suffer from NP and discuss the clinical applications of this topical approach. EXPERT OPINION: Overall, the capsaicin 8% dermal patch is as effective in reducing pain intensity as other centrally active agents (i.e. pregabalin). Some studies have also reported fewer systemic side effects, a faster onset of action and superior treatment satisfaction compared with systemic agents. In our opinion, capsaicin 8% dermal patches also present additional advantages, such as a good systemic tolerability, the scarcity of adverse events, the possibility to combine it with other agents, and a good cost-effective profile. It is important to note that, as the mechanism of action of capsaicin 8% is the 'defunctionalization' of small afferent fibers through interaction with TRPV1 receptors, the peripheral expression of this receptor on nociceptor fibers, is crucial to predict patient's response to treatment.

Dynamic Mechanical Allodynia--One Clinical Sign, Several Mechanisms: Five Illustrative Cases.

Pain evoked by tangential movement across the skin is usually defined as dynamic mechanical allodynia (DMA). Some patients complain of DMA as troublesome as spontaneous pain and refer a marked interfering with activities of daily living and sleep. Pathophysiology of DMA is complex and can be related to several mechanisms, both nociceptive and neuropathic. Five exemplificative clinical cases of DMA are presented, each associated to a possible specific mechanism: injured skin DMA, peri-injured skin DMA, far injury DMA, nerve-confined DMA and fear DMA (pseudo allodynia). The identification of these subcategories of DMA can stimulate further studies aimed at evaluating the usefulness of a mechanism-based therapy for the different clinical forms of DMA.

Excessive daytime sleepiness in patients on intrathecal analgesia for chronic pain.

OBJECTIVES: Intrathecal (IT) drug administration is an advanced technique in pain treatment algorithm for patients poorly responsive to systemic pharmacological treatment or less invasive techniques. The aim is to improve analgesia lowering side effects; despite this premise, many side effects of long-term IT therapy have been described, mainly related to opioid administration. We observed, in some of the patients regularly followed for pump refills in our Pain Unit, the appearance of excessive daytime sleepiness (EDS) interfering with daily life and work activity; this study aims to investigate the incidence of EDS in patients on IT analgesia with opioid or non-opioid drugs and its possible relationship with respiratory problems during sleep. MATERIALS AND METHODS: 21 patients on IT therapy for chronic pain answered the Epworth Sleepiness Scale (ESS). The incidence of EDS in patients receiving IT opioids was compared to a control group not receiving opioids. In 10 patients, who performed polysomnography (PSG) and maintenance of wakefulness test (MWT) for sleep complaints, we studied the relationship between PSG data and ESS scores and we verified the concordance of ESS and MWT results. RESULTS: 38% of the patients reported EDS, according to ESS data; all the patients with EDS were receiving an IT opioid. Even if some patients presented sleep apneas, we failed to correlate this data with daytime sleepiness. Subjective sleepiness is confirmed by the results of MWT. CONCLUSION: Our data demonstrate that EDS is a frequent and important side effect of IT analgesia and it seems related to opioids administration.

[Pain in urology: pathophysiological aspects of pain and chronicity.] / Il dolore in ambito urologico: aspetti fisiopatologici del dolore e della cronicità

Chronic pain has been traditionally defined by pain duration, but this approach has limited empirical support and does not account for chronic pain multidimensionality. Defining chronic pain solely by duration is based on the view that acute pain signals potential tissue damage, whereas chronic pain results from central sensitization in which pain is sustained after nociceptive inputs have diminished. Chronic urological pain is a prevalent condition, which can represent a major challenge to health care providers due to its complex aetiology and poor response to therapy. In most cases, clear signs of on-going tissue trauma, inflammation or infection are not present. Despite this, more underhanded pathophysiological mechanisms, affecting the urinary system or other pelvic organ systems (musculoskeletal, neurologic, urologic, gynaecologic) and some psychological aspects may be present. In this article, some pathophysiological aspects of visceral pain are discussed; the definition of 'chronic pain', the mechanism of action of drugs used in the treatment of pain and the rationale for association therapy are also reviewed.

Breakthrough cancer pain (BTcP): a synthesis of taxonomy, pathogenesis, therapy, and good clinical practice in adult patients in Italy.

Pain presents in 80% of patients with advanced cancer, and 30% have periods of increased pain due to fluctuating intensity, known as breakthrough cancer pain (BTcP). BTcP is high-intensity, short-duration pain occurring in several episodes per day and is non-responsive to treatment. The clinical approach to BTcP is variable. A review of the literature was performed to provide clinicians and practitioners with a rational synthesis of the ongoing scientific debate on BTcP and to provide a basis for optimal clinical approach to BTcP in adult Italian patients. Data show that circadian exacerbations of pain should be carefully monitored, differentiating, if possible, between fluctuations of background pain (BP), end-of-dose effect, and BTcP. BTcP should be monitored in all care contexts in clinical practice and each care facility must have all the medications and products approved for use in BTcP at their disposal. Data show that knowledge about medications for BTcP is lacking: medications for BTcP treatment are not interchangeable, although containing the same active substance; each physician must know the specific characteristics of each medication, its pharmacological properties, limitations in clinical practice, specifics relating to titration and repeatability of administration, and technical specifics relating to the accessibility and delivery. Importantly, before choosing a rapid-onset opioid (ROO), it is essential to deeply understand the status of patient and the characteristics of their family unit/caregivers, taking into account the patient's progressive loss of autonomy and/or cognitive-relational functionality. When BTcP therapy is initiated or changed, special attention must be paid to training the patient and family members/caregivers, providing clear instructions regarding the timing of drug administration. The patient must already be treated effectively with opioids before introducing ROOs for control of BTcP.

Dynamic mechanical allodynia following finger amputation: Unexpected skin hyperinnervation.

The development of chronic pain after amputations is not an uncommon event. In some cases the most disabling problem is represented by the symptom called dynamic mechanical allodynia, characterized by the painful sensation evoked by gently stroking the skin. Despite the growing interest in understanding pain mechanisms, little is known about the mechanism sustaining this peculiar type of pain. We present here the case of a 53-year-old female patient who complained of severe tactile allodynia in the hand after amputation of her left second finger, resistant to several medical and surgical treatments. In order to gain information about the pain mechanism, two neurodiagnostic skin biopsies were obtained from the area of tactile allodynia and from the contralateral, normal skin area. Skin biopsies showed an unexpected increased innervation of the allodynic skin compared to the contralateral, normal skin area (+ 80.1%). Hyperinnervation has been proposed as a mechanism of pain following nerve lesions, but the increased innervation described here could be also attributed to neuronal plasticity occurring in chronic inflammatory conditions. Independently from the uncertain cause of the epidermal hyperinnervation, in this patient we tried to reduce the elevated number of epidermal nerve fibres by treating the skin with topical capsaicin (0.075%) three times a day, and obtained a persistent pain relief. In conclusion, neurodiagnostic skin biopsy might represent an useful tool for detecting derangements of epidermal innervation in patients with dynamic mechanical allodynia and can help to select an individually tailored therapeutic strategy in such difficult clinical conditions. Further studies are needed to clarify this issue and try to gain better understanding of chronic pain mechanisms in patients who underwent finger amputation.

Allodynic skin in post-herpetic neuralgia: histological correlates.

Most post-herpetic neuralgia (PHN) patients suffer from tactile allodynia (pain evoked by lightly touching the skin) and it is frequently the dominant clinical manifestation. The pathophysiology of tactile allodynia in PHN patients is poorly understood and this is one of the major limits to the development of appropriate therapies. Epidermal nerve fibres (ENFs) are free nerve endings of small-diameter A-delta and C primary afferents, which can easily be assessed by neurodiagnostic skin biopsy (NSB). The aim of this study was to establish the correlation between the residual epidermal innervation of the allodynic skin and the intensity of tactile allodynia in that area. Twenty-five patients (13 males and 12 females) with PHN were enrolled. Eighteen patients had PHN in the thoracic dermatome, four in the cervical, two in the trigeminal and one in the lumbar. The severity of allodynia evoked by a paintbrush was graded according to an eleven-point numerical scale. A skin biopsy was obtained from the maximal allodynia area and from the contralateral skin. Nerve fibres were labelled with indirect immunofluorescence. Results showed that epidermal innervation was lower in the allodynic skin than in the contralateral skin, although there was great variability among patients. There was no correlation between severity of allodynia and epidermal innervation of the PHN skin. In conclusion, the present study further indicates peripheral nervous system involvement in PHN but does not support a direct correlation between epidermal innervation changes and tactile allodynia.

Tapentadol in the management of chronic low back pain: a novel approach to a complex condition?

Chronic pain affects approximately 1 in 5 people in Europe, and around half of sufferers receive inadequate pain management. The most common location is the lower back. Pharmacological treatment of this condition is challenging because of the range of causative mechanisms and the difficulty of balancing analgesic efficacy and tolerability. An international panel of clinical pain specialists met in September, 2009, to discuss the treatment of chronic low back pain, and to review preclinical and clinical data relating to the new analgesic, tapentadol. A lack of consensus exists on the best treatment for low back pain. The range of regularly prescribed pharmacological agents extends from nonopioids (paracetamol, NSAIDs, and COX-2 inhibitors) to opioids, antidepressants and anticonvulsants. Pain relief may be compromised, however, by an undetected neuropathic component or intolerable side effects. Treatment is potentially life-long and effective analgesics are urgently needed, with demonstrable long-term safety. Combining separate agents with different mechanisms of action could overcome the limitations of present pharmacological therapy, but clinical evidence for this approach is currently lacking. Tapentadol combines µ-opioid agonism with noradrenaline reuptake inhibition in a single molecule. There is strong evidence of synergistic antinociception between these two mechanisms of action. In preclinical and clinical testing, tapentadol has shown efficacy against both nociceptive and neuropathic pain. Preclinical data indicate that tapentadol's µ-opioid agonism makes a greater contribution to analgesia in acute pain, while noradrenaline reuptake inhibition makes a greater contribution in chronic neuropathic pain models. Tapentadol also produces fewer adverse events than oxycodone at equianalgesic doses, and thus may have a 'µ-sparing effect'. Current evidence indicates that tapentadol's efficacy/tolerability ratio may be better than those of classical opioids. However, further research is needed to establish its role in pain management.

Chronic pain therapy and hypothalamic-pituitary-adrenal axis impairment.

Opiates and/or nonsteroidal anti-inflammatory drugs (NSAIDs) are among the most effective therapies for chronic pain, but their prolonged time of use can affect health conditions through physical and psychological side effects. They include the very common gastrointestinal effects and changes that can induce osteoporosis, depression, impaired cognition and a generally poor quality of life, which per se can induce and maintain a chronic painful condition. For this reason it is becoming imperative to expand our knowledge of the interaction of these substances with body functions apparently not directly involved in nociception and pain, such as neuroendocrine functions. The purpose of this study was to determine, in male and female patients suffering from chronic pain, the effect of conventional pain therapy (opiates, NSAIDs) on hypothalamic-pituitary-adrenal (HPA) axis function. This was assessed by measuring the blood levels of adrenal-related hormones (adrenocorticotrophin hormone, ACTH; cortisol; dehydroepiandrosterone, DHEA and dehydroepiandrosterone sulfate, DHEAS). The second purpose of the study was to test the hypothesis that these hormones are associated with the psychological profile shown by the chronic pain patients. The results showed significant changes induced by pain therapy on the HPA axis: ACTH, cortisol, DHEA and DHEAS blood levels decreased in all subjects taking opiates or NSAIDs to treat pain. Moreover these changes showed significant correlations with psychological features of the subjects depending on age and sex.

Italian registry on long-term intrathecal ziconotide treatment.

BACKGROUND: Ziconotide is commonly used for intrathecal (IT) therapy of chronic pain, and has been recently indicated as a first-line IT drug. It is also extremely useful for patients intolerant or refractory to the common IT drugs (such as morphine). The literature, excluding registration studies, mostly includes small samples, and gives only fragmentary evidence on the long-term risks and benefits of ziconotide. OBJECTIVE: To collect data on safety and efficacy of long-term ziconotide IT infusion in Italian pain centers. STUDY DESIGN: Retrospective cohort study on the use of ziconotide in Italy. The study was designed and coordinated by the Foundation ISAL (Algological Sciences Research and Training Institute). Patients treated with ziconotide from several pain therapy and neurosurgery units were included in the study, allowing the creation of the first Italian Registry of Ziconotide. SETTING: Seventeen Italian public and private pain and neurosurgery centers. METHODS: Patients suffering from cancer or non-cancer intractable chronic pain who had been treated with ziconotide IT infusion for at least one month. Efficacy was analyzed considering changes on the visual analog scale of pain intensity from baseline observation. Safety was assessed by monitoring the number and intensity of adverse events. RESULTS: Currently, 104 patients are included in the Italian Registry of Ziconotide. Ziconotide was administered as the first IT drug choice to 55 patients. Seventy-two patients reported at least a 30% pain intensity reduction with a mean dose of 4.36 ug/d. The sustained analgesic effect (P < 0.001) of the ziconotide IT therapy was observed in a group of 45 patients who remained in the study over 6 months without treatment interruptions and with relatively stable doses. Sixty-six patients reported at least one side effect related to ziconotide. However, adverse events have not always been decisive for treatment interruptions. LIMITATIONS: Data were collected retrospectively from different pain centers that used different methods for ziconotide treatment and clinical forms for its data collection; for this reason there is an absence of standardized methodologies and a placebo-controlled group, and some data were missing. CONCLUSIONS: Ziconotide IT therapy is a treatment option commonly used for clinical practice in 17 Italian pain therapy and neurosurgery units. It might give relief to patients with refractory chronic pain, and it seems to have a safe profile. Long-term studies and controlled trials are required.

Development of the Italian version of the Tampa Scale of Kinesiophobia (TSK-I): cross-cultural adaptation, factor analysis, reliability, and validity.

STUDY DESIGN: Evaluation of the psychometric properties of a translated and culturally adapted questionnaire. OBJECTIVE: Translating, culturally adapting, and validating the Italian version of the Tampa Scale of Kinesiophobia (TSK-I) to allow its use for Italian-speaking patients with low back pain. SUMMARY OF BACKGROUND DATA: Increasing attention is being given to standardized outcome measures as a means of improving interventions for low back pain. A translated form of the TSK in patients with low back pain has never been validated in the Italian population. METHODS: The development of the TSK-I questionnaire involved its translation and back-translation, a final review by an expert committee, and testing of the prefinal version to establish its correspondence to the original English version. Psychometric testing included factor analysis, reliability by internal consistency (Cronbach's alpha) and test-retest repeatability (Intraclass Coefficient Correlation), discriminant validity (Pearson correlation) by comparing TSK-I to a visual analogue scale, the Roland Morris Disability Questionnaire, Beck's Depression Inventory and Anxiety Inventory. RESULTS: It took the authors 5 months to achieve a shared version of the TSK-I, which proved to be satisfactorily acceptable when administered to 178 subjects. Factor analysis indicated a 2-factor 13-item solution (38% of explained variance). The questionnaire showed acceptable internal consistency (alpha = 0.772) and high test-retest reliability (ICC = 0.956). Discriminant validity showed moderate to low correlations with visual analogue scale (r = 0.345), the Roland Morris Disability (r = 0.337), and Beck's Depression Inventory and Anxiety Inventory (r = 0.258 and r = 283). The subscales were also psychometrically analyzed. CONCLUSION: The TSK was successfully translated into Italian, showing a good factorial structure and psychometric properties, and replicating the results of existing English versions of the questionnaire. Its use is recommended for research purposes.

Vertebral body innervation: Implications for pain.

Vertebral fractures often cause intractable pain. To define the involvement of vertebral body innervation in pain, we collected specimens from male and female patients during percutaneous kyphoplasty, a procedure used for reconstruction of the vertebral body. Specimens were taken from 31 patients (9 men and 22 women) suffering high-intensity pain before surgery. In total, 1,876 histological preparations were obtained and analysed. Immunohistochemical techniques were used to locate the nerves in the specimens. The nerve fibres were labelled by indirect immunofluorescence with the primary antibody directed against Protein Gene Product 9.5 (PGP 9.5), a pan-neuronal marker; another primary antibody directed against type IV collagen (Col IV) was used to identify vessels and to determine their relationship with vertebral nerve fibres. The mean percentage of samples in which it was possible to identify nerve fibres was 35% in men and 29% in women. The percentages varied depending on the spinal level considered and the sex of the subject, nerve fibres being mostly present around vessels (95%). In conclusion, there is scarce innervation of the vertebral bodies, with a clear prevalence of fibres located around vessels. It seems unlikely that this pattern of vertebral body innervation is involved in vertebral pain or in pain relief following kyphoplasty.

Peripheral subcutaneous neurostimulation in the management of neuropathic pain: five case reports.

Introduction. Spinal cord stimulation (SCS) is an effective treatment option for neuropathic pain. However, because of the obvious procedural issues, SCS is unable to reach certain areas, such as the face, thorax, coccyx, the cervico-dorsal and lumbar areas, and the sacral, abdominal, and inguinal regions. On the other hand, these areas are easily reached by subcutaneous field stimulation. Methodology. We report the analgesic results, using a visual analog scale (VAS), of five patients with neuropathic pain treated with subcutaneous field stimulation to the area. We also discuss the probable mechanism of action, and highlight the technical issues inherent to this approach. Results. Significant pain reduction and reduction in analgesic medication were reported in all patients during the study period, with VAS scores consistently lowered by more than 50% from baseline levels. As a result of pain reduction, the patients' quality of life improved. There were no adverse events reported except for early electrode array displacement in two of our patients. Conclusion. When SCS is not appropriate for certain neuropathic pain syndromes, subcutaneous field stimulation may be used with some degree of efficacy.