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Neuropathic pain is more prevalent in women. However, females are under-represented in animal experiments, and the mechanisms of sex differences remain inadequately understood. We used the spared nerve injury (SNI) model in rats to characterize sex differences in pain behaviour, unbiased RNA-Seq and proteomics to study the mechanisms. Male and female rats were subjected to SNI- and sham-surgery. Mechanical and cold allodynia were assessed. Ipsilateral lumbar dorsal root ganglia (DRG) and spinal cord (SC) segments were collected for RNA-seq analysis with DESeq2 on Day 7. Cerebrospinal fluid (CSF) samples for proteomic analysis and DRGs and SCs for analysis of IB-4 and CGRP, and IBA1 and GFAP, respectively, were collected on Day 21. Females developed stronger mechanical allodynia. There were no differences between the sexes in CGRP and IB-4 in the DRG or glial cell markers in the SC. No CSF protein showed change following SNI. DRG and SC showed abundant changes in gene expression. Sexually dimorphic responses were found in genes related to T-cells ( cd28 , ctla4 , cd274 , cd4 , prf1 ), other immunological responses ( dpp4 , c5a , cxcr2 and il1b ), neuronal transmission ( hrh3 , thbs4 , chrna4 and pdyn ), plasticity ( atf3, c1qc and reg3b ), and others ( bhlhe22 , mcpt1l, trpv6 ). We observed significantly stronger mechanical allodynia in females and numerous sexually dimorphic changes in gene expression following SNI in rats. Several genes have previously been linked to NP, while some are novel. Our results suggest gene targets for further studies in the development of new, possibly sex-specific, therapies for NP.

Purpose We performed a detailed analysis of sensory function in patients with chronic post-surgical neuropathic pain (NP) after breast cancer treatments by quantitative sensory testing (QST) with DFNS (German Research Network on Neuropathic Pain) protocol and bed side examination (BE). The nature of sensory changes in peripheral NP may reflect distinct pathophysiological backgrounds that can guide the treatment choices. NP with sensory gain (i.e., hyperesthesia, hyperalgesia, allodynia) has been shown to respond to Na + -channel blockers (e.g., oxcarbazepine). Methods 104 patients with at least “probable” NP in the surgical area were included. All patients had been treated for breast cancer 4–9 years ago and the handling of the intercostobrachial nerve (ICBN) was verified by the surgeon. QST was conducted at the site of NP in the surgical or nearby area and the corresponding contralateral area. BE covered the upper body and sensory abnormalities were marked on body maps and digitalized for area calculation. The outcomes of BE and QST were compared to assess the value of QST in the sensory examination of this patient group. Results Loss of function in both small and large fibers was a prominent feature in QST in the area of post-surgical NP. QST profiles did not differ between spared and resected ICBN. In BE, hypoesthesia on multiple modalities was highly prevalent. The presence of sensory gain in BE was associated with more intense pain. Conclusions Extensive sensory loss is characteristic for chronic post-surgical NP several years after treatment for breast cancer. These patients are unlikely to respond to Na + -channel blockers.

It has been suggested that placebo analgesia involves both higher order cognitive networks and endogenous opioid systems. The rostral anterior cingulate cortex (rACC) and the brainstem are implicated in opioid analgesia, suggesting a similar role for these structures in placebo analgesia. Using positron emission tomography, we confirmed that both opioid and placebo analgesia are associated with increased activity in the rACC. We also observed a covariation between the activity in the rACC and the brainstem during both opioid and placebo analgesia, but not during the pain-only condition. These findings indicate a related neural mechanism in placebo and opioid analgesia.

An expert working group of the European Association for Palliative Care has revised and updated its guidelines on the use of morphine in the management of cancer pain. The revised recommendations presented here give guidance on the use of morphine and the alternative strong opioid analgesics which have been introduced in many parts of the world in recent years. Practical strategies for dealing with difficult situations are described presenting a consensus view where supporting evidence is lacking. The strength of the evidence on which each recommendation is based is indicated.

Background: Persistent postsurgical pain can have a significant effect on the quality of life of women being treated for breast cancer. The aim of this prospective study was to develop a screening tool to identify presurgical demographic, psychological and treatment-related factors that predict persistence of significant pain in the operated area after 6 months from surgery. Methods: Background and self-reported questionnaire data were collected the day before surgery and combined with treatment-related data. Pain in the operated area was assessed 6 months after surgery with a questionnaire. The Bayesian model was used for the development of a screening tool. Results: Report of preoperative chronic pain, more than four or more previous operations, preoperative pain in the area to be operated, high body mass index, previous smoking and older age were included in the six-factor model that best predicted significant pain at the follow-up in the 489 women studied. Conclusion: A six-factor risk index was developed to estimate the risk of developing significant pain after breast cancer surgery. Neither treatment- nor mood-related variables were included in the model. Identification of risk factors may lead to prevention of persistent postsurgery pain. This tool could be used for target prevention to those who are at the highest risk of developing persistent postsurgery pain.

Neuropathic pain can have many causes (box 1),1 with diabetic neuropathy among the commonest. The International Association of the Study of Pain defines neuropathic pain as 'pain caused by a lesion or disease of the somatosensory system'.2 This article focuses on drugs for treating neuropathic pain, mainly antiepileptics and antidepressants, including those used off-label in the UK (box 2). National Institute for Health and Care Excellence (NICE) guidance1 recommends offering a choice of amitriptyline, duloxetine, gabapentin, or pregabalin as initial treatment, with switching between these drugs if pain relief is not obtained or the treatment not tolerated. Successful clinical management requires balancing the benefits and adverse effects of available drugs, lifestyle interventions, and treating the underlying cause if possible. Possible comorbidities (anxiety, depression) need to be considered when choosing the best treatment for an individual patient.

Abstract Objectives: To compare patients' preference for transdermal fentanyl or sustained release oral morphine, their level of pain control, and their quality of life after treatment. Design: Randomised, multicentre, international, open label, crossover trial. Setting: 35 centres in Belgium, Canada, Denmark, Finland, the United Kingdom, the Netherlands, and South Africa. Participants: 256 patients (aged 26-82 years) with chronic non-cancer pain who had been treated with opioids. Main outcome measures: Patients' preference for transdermal fentanyl or sustained release oral morphine, pain control, quality of life, and safety assessments. Results: Of 212 patients, 138 (65%) preferred transdermal fentanyl, whereas 59 (28%) preferred sustained release oral morphine and 15 (7%) expressed no preference. Better pain relief was the main reason for preference for fentanyl given by 35% of patients. More patients considered pain control as being “good” or “very good” with fentanyl than with morphine (35% v 23%, P=0.002). These results were reflected in both patients' and investigators' opinions on the global efficacy of transdermal fentanyl. Patients receiving fentanyl had on average higher quality of life scores than those receiving morphine. The incidence of adverse events was similar in both treatment groups; however, more patients experienced constipation with morphine than with fentanyl (48% v 29%, P<0.001). Overall, 41% of patients experienced mild or moderate cutaneous problems associated with wearing the transdermal fentanyl patch, and more patients withdrew because of adverse events during treatment with fentanyl than with morphine (10% v 5%). However, within the subgroup of patients naive to both fentanyl and morphine, similar numbers of patients withdrew owing to adverse effects (11% v 10%, respectively). Conclusion: Transdermal fentanyl was preferred to sustained release oral morphine by patients with chronic non-cancer pain previously treated with opioids. The main reason for preference was better pain relief, achieved with less constipation and an enhanced quality of life. What is already known on this topic The clinical use of potent opioids in the treatment of chronic non-cancer pain is supported by retrospective, survey data and small randomised controlled trials showing efficacy and safety Studies with transdermal fentanyl have shown efficacy and preference over sustained release oral morphine in the treatment of cancer pain What this study adds This is the first study to provide comparative data supporting treatment options with potent opioids for chronic non-cancer pain Both transdermal fentanyl and sustained release oral morphine provided effective and well tolerated pain relief During fentanyl treatment patients experienced superior pain relief, higher quality of life, and less constipation; fentanyl was preferred to morphine by 65% of patients

Our mistake is to treat chronic pain as if it were acute or end of life pain

Breakthrough pain (BKP) is a transitory flare of pain that occurs on a background of relatively well controlled baseline pain. Previous surveys have found that BKP is highly prevalent among patients with cancer pain and predicts more severe pain, pain-related distress and functional impairment, and relatively poor quality of life. An international group of investigators assembled by a task force of the International Association for the Study of Pain (IASP) evaluated the prevalence and characteristics of BKP as part of a prospective, cross-sectional survey of cancer pain. Fifty-eight clinicians in 24 countries evaluated a total of 1095 patients with cancer pain using patient-rated items from the Brief Pain Inventory (BPI) and observer-rated measures. The observer-rated information included demographic and tumor-related data, the occurrence of BKP, and responses on checklists of pain syndromes and pathophysiologies. The clinicians reported BKP in 64.8% of patients. Physicians from English-speaking countries were significantly more likely to report BKP than other physicians. BKP was associated with higher pain scores and functional interference on the BPI. Multivariate analysis showed an independent association of BKP with the presence of more than one pain, a vertebral pain syndrome, pain due to plexopathy, and English-speaking country. These data confirm the high prevalence of BKP, its association with more severe pain and functional impairment, and its relationship to specific cancer pain syndromes. Further studies are needed to characterize subtypes of BKP. The uneven distribution of BKP reporting across pain specialists from different countries suggests that more standardized methods for diagnosing BKP are needed.

Neuropathic pain is caused by a lesion or disease of the somatosensory system, including peripheral fibres (Aβ, Aδ and C fibres) and central neurons, and affects 7–10% of the general population. Multiple causes of neuropathic pain have been described and its incidence is likely to increase owing to the ageing global population, increased incidence of diabetes mellitus and improved survival from cancer after chemotherapy. Indeed, imbalances between excitatory and inhibitory somatosensory signalling, alterations in ion channels and variability in the way that pain messages are modulated in the central nervous system all have been implicated in neuropathic pain. The burden of chronic neuropathic pain seems to be related to the complexity of neuropathic symptoms, poor outcomes and difficult treatment decisions. Importantly, quality of life is impaired in patients with neuropathic pain owing to increased drug prescriptions and visits to health care providers, as well as the morbidity from the pain itself and the inciting disease. Despite challenges, progress in the understanding of the pathophysiology of neuropathic pain is spurring the development of new diagnostic procedures and personalized interventions, which emphasize the need for a multidisciplinary approach to the management of neuropathic pain. Neuropathic pain is caused by a lesion or disease of the somatosensory system (including peripheral and central neurons). Here, the authors present the current descriptions of the presentation, causes, diagnosis and treatment of neuropathic pain with a focus on peripheral neuropathic pain, which has a greater knowledge base than central neuropathic pain.