Pain and diet: A summary of the evidence for the role of diet modification in chronic pain.

Chronic pain constitutes a significant burden to patients and healthcare systems. For many patients, the only option is to attempt to manage their pain within their daily lives. Here, we review evidence provided by three systematic reviews for the effect of diet and diet supplements on patients' experience of chronic pain.

Cultures of Human Skin Mast Cells, an Attractive In Vitro Model for Studies of Human Mast Cell Biology.

Studies of mast cell biology are dependent on relevant and validated in vitro models. Here, we present detailed information concerning the phenotype of both freshly isolated human skin mast cells (MCs) and of in vitro cultures of these cells that were obtained by analyzing their total transcriptome. Transcript levels of MC-related granule proteins and transcription factors were found to be remarkably stable over a 3-week culture period. Relatively modest changes were also seen for important cell surface receptors including the high-affinity receptor for IgE, FCER1A, the low-affinity receptor for IgG, FCGR2A, and the receptor for stem cell factor, KIT. FCGR2A was the only Fc receptor for IgG expressed by these cells. The IgE receptor increased by 2-5-fold and an approximately 10-fold reduction in the expression of FCGR2A was observed most likely due to the cytokines, SCF and IL-4, used for expanding the cells. Comparisons of the present transcriptome against previously reported transcriptomes of mouse peritoneal MCs and mouse bone marrow-derived MCs (BMMCs) revealed both similarities and major differences. Strikingly, cathepsin G was the most highly expressed granule protease in human skin MCs, in contrast to the almost total absence of this protease in both mouse MCs. Transcript levels for the majority of cell surface receptors were also very low compared to the granule proteases in both mouse and human MCs, with a difference of almost two orders of magnitude. An almost total absence of T-cell granzymes was observed in human skin MCs, indicating that granzymes have no or only a minor role in human MC biology. Ex vivo skin MCs expressed high levels of selective immediate early genes and transcripts of heat shock proteins. In validation experiments, we determined that this expression was an inherent property of the cells and not the result of the isolation process. Three to four weeks in culture results in an induction of cell growth-related genes accompanying their expansion by 6-10-fold, which increases the number of cells for in vitro experiments. Collectively, we show that cultured human skin MCs resemble their ex vivo equivalents in many respects and are a more relevant in vitro model compared to mouse BMMCs for studies of MC biology, in particular human MC biology.

CREB Is Indispensable to KIT Function in Human Skin Mast Cells-A Positive Feedback Loop between CREB and KIT Orchestrates Skin Mast Cell Fate.

Skin mast cells (MCs) are critical effector cells in acute allergic reactions, and they contribute to chronic dermatoses like urticaria and atopic and contact dermatitis. KIT represents the cells' crucial receptor tyrosine kinase, which orchestrates proliferation, survival, and functional programs throughout the lifespan. cAMP response element binding protein (CREB), an evolutionarily well-conserved transcription factor (TF), regulates multiple cellular programs, but its function in MCs is poorly understood. We recently reported that CREB is an effector of the SCF (Stem Cell Factor)/KIT axis. Here, we ask whether CREB may also act upstream of KIT to orchestrate its functioning. Primary human MCs were isolated from skin and cultured in SCF+IL-4 (Interleukin-4). Pharmacological inhibition (666-15) and RNA interference served to manipulate CREB function. We studied KIT expression using flow cytometry and RT-qPCR, KIT-mediated signaling using immunoblotting, and cell survival using scatterplot and caspase-3 activity. The proliferation and cycle phases were quantified following BrdU incorporation. Transient CREB perturbation resulted in reduced KIT expression. Conversely, microphthalmia transcription factor (MITF) was unnecessary for KIT maintenance. KIT attenuation secondary to CREB was associated with heavily impaired KIT functional outputs, like anti-apoptosis and cell cycle progression. Likewise, KIT-elicited phosphorylation of ERK1/2 (Extracellular Signal-Regulated Kinase 1/2), AKT, and STAT5 (Signal Transducer and Activator of Transcription) was substantially diminished upon CREB inhibition. Surprisingly, the longer-term interference of CREB led to complete cell elimination, in a way surpassing KIT inhibition. Collectively, we reveal CREB as non-redundant in MCs, with its absence being incompatible with skin MCs' existence. Since SCF/KIT regulates CREB activity and, vice versa, CREB is required for KIT function, a positive feedforward loop between these elements dictates skin MCs' fate.

Pharmacotherapy of Painful Diabetic Neuropathy: A Clinical Update.

The rising prevalence of diabetes mellitus (DM) leads on to an increase in chronic diabetic complications. Diabetic peripheral neuropathies (DPNs) are common chronic complications of diabetes. Distal symmetric polyneuropathy is the most prevalent form. Most patients with DPN will remain pain-free; however, painful DPN (PDPN) occurs in 6-34% of all DM patients and is associated with reduced health-related-quality-of-life and substantial economic burden. Symptomatic treatment of PDPN and diabetic autonomic neuropathy is the key treatment goals. Using certain patient related characteristics, subjects with PDPN can be stratified and assigned targeted therapies to produce better pain outcomes. The aim of this review is to discuss the various pathogenetic mechanisms of DPN with special reference to the mechanisms leading to PDPN and the various pharmacological and non-pharmacological therapies available for its management. Recommended pharmacological therapies include anticonvulsants, antidepressants, opioid analgesics, and topical medications.

Non-pharmacological interventions for managing pain in community-dwelling older adults.

Pain is a complex and common issue within older adults. This complexity can be a direct result of comorbidities and the subsequent polypharmacy. The effective control of pain in older adults needs more than just pharmacological management. Non-pharmacological interventions have been demonstrated to be beneficial when combined with pain medications. This commentary critically appraises a systematic review that examines the effectiveness of non-pharmacological interventions for the management of pain in community dwelling older adults.

A retrospective study evaluating the trend of opioid prescribing in low back pain at a UK teaching hospital.

INTRODUCTION: Current data suggest that the chronic use of strong opioids in low back pain (LBP) is increasing. There is evidence for the use of opioids in the initial management of LBP, but the efficacy in the long term is unknown. This article intends to examine the use of opioids in patients with chronic LBP over a period of three doctor-led clinics. METHODS: Single-center retrospective cohort study following 200 patients through the pain clinic at a UK teaching hospital for more than two clinic visits, up to a maximum of three. Data concerning demographics, pain scores, medication changes, and clinic outcome. RESULTS: Data collected showed that there was a significant correlation between baseline morphine equivalent amount (MEA) and final clinic MEA; initial pain scores and final clinic MEA; cause of LBP and final clinic LBP; and traumatic LBP and absolute change in MEA. There was no association between number of physical interventions and MEA. The sample also showed an average absolute change in MEA by 2.93 ± 57.86 mg. The proportion of patients with a MEA of >50 mg/d increased from 24 to 29 percent. The proportion of patients on opioids at least one opioid increased by 10 percent. CONCLUSIONS: Significant predictors of final clinic MEA were initial pain scores, baseline MEA, and the cause of LBP. Duration of pain was a poor predictor of MEA. There was no association between MEA and number of interventions. In this cohort, the trend seems to be increasing the number and dose of opioids in patients with LBP.

Using patient experiences to develop services for chronic pain.

PURPOSE: The aim of this study was to improve the overall experience for patients using chronic pain services at a large teaching hospital in England. Experience-based co-design methodology was used to gain a greater understanding of patients' experiences and to produce a list of priorities for change when improving the patient experience. METHOD: A total of seven video-recorded patient interviews were conducted to capture a range of patient experiences of using the chronic pain service. The interviews were analysed to identify 'touchpoints' which are areas in which patients experienced a heightened emotional response to their interaction with the service or staff. A short trigger film was compiled to illustrate these touchpoints to staff and gain their commitment to improve patients' experiences when using the service. A patient experience event was held at which patients discussed the touchpoints and identified the most significant areas for change that would improve their experiences of using the chronic pain service. RESULTS: A wide range of touchpoints were identified. The lack of information provided before arriving for a procedure and the need for a short debrief after clinic were prioritised for improvement. Patients valued the development of good relationships with clinic staff and feeling properly listened to for the first time. The patient experience event allowed the key points patients would like to know before a procedure, to be drawn up in a list, which could be passed onto staff. CONCLUSION: This study featured collaboration between patients and staff to improve patients' experiences of using chronic pain services. Through patient participation, a comprehensive list of recommendations for service improvement was produced, and possible solutions were identified. The involvement of patients in driving change and re-designing services is shaping a more patient-centred chronic pain clinic and improving the experience for all the patients who use the service.

Prolonged-release oxycodone/naloxone reduces opioid-induced constipation and improves quality of life in laxative-refractory patients: results of an observational study.

BACKGROUND: Opioids are an effective treatment for moderate-to-severe pain. However, they are associated with a number of gastrointestinal side effects, most commonly constipation. Laxatives do not target the underlying mechanism of opioid-induced constipation (OIC), so many patients do not have their symptoms resolved. Fixed-dose prolonged-release (PR) oxycodone/naloxone (OXN) tablets contain the opioid agonist oxycodone and the opioid antagonist naloxone. Nal-oxone blocks the action of oxycodone in the gut without compromising its analgesic effects. AIM: To evaluate the effectiveness of PR OXN in patients with severe pain who had laxative-refractory OIC with their previous opioid. METHODS: The study was carried out in 13 centers across the UK and Ireland, using a bespoke online tool to capture patients' data. Patients were reviewed according to normal clinical practice of each center and rated any changes in their constipation and quality of life (QoL) since starting PR OXN. Any change in patients' laxative use was also recorded. RESULTS: One hundred and seven patients were entered into the database, and 81 went on to attend at least one review. Of these, 54 (66.7%) reported an improvement in constipation and 50 (61.7%) reported an improvement in QoL since starting PR OXN. Fifty-seven patients (70.4%) said they had reduced laxative intake; 48 (59.3%) only needed laxatives as required. CONCLUSION: PR OXN reduced symptoms of constipation, improved QoL and reduced laxative intake in patients with OIC. It has a potential place early in any treatment strategy for severe pain in patients using opioids, particularly in patients who may be predisposed to constipation.

Oxycodone and Naloxone Combination: A 12-Week Follow-up in 20 Patients Shows Effective Analgesia Without Opioid-Induced Bowel Dysfunction.

INTRODUCTION: Opioid analgesics are widely regarded to be highly effective but are equally known for their side effects on the bowel. A new combination of the opioid analgesic oxycodone and naloxone has been developed to combat opioid-induced bowel dysfunction (OIBD) whilst still being effective as an analgesic. The aim of this observational study was to assess the analgesic efficacy of this new combination and to analyze its effect on bowel function. METHODS: Twenty-six patients underwent a trial of this new combination, with 21 patients reaching week 8 and 18 reaching week 12. RESULTS: A significant reduction was seen in the pain severity score at weeks 4, 8, and 12 (P < 0.05), and a significant improvement in the bowel function index was again seen at these points (P < 0.001 at week 4 and 12, P < 0.05 at week 8). In the patients' global impression of change, 83.3% of patients rated the new medication as an improvement compared to their previous regimen, and 87.5% rated it overall as "good" or "very good." CONCLUSION: This small single-center study suggests that the use of ONC in selected patients could lead to an improvement in pain severity and pain interference with a significant improvement in OIBD. Compliance with the combination is good, and it is generally well tolerated.

Assessment of Transdermal Buprenorphine Patches for the Treatment of Chronic Pain in a UK Observational Study.

BACKGROUND: Opioids provide effective analgesia for moderate-to-severe, chronic pain. Transdermal buprenorphine (TDB) is available in the UK as weekly, lower-dose (5-20 µg/h) patches and twice-weekly, higher dose (35-70 µg/h) patches. This prospective, observational, multicenter study of patients with various chronic pain conditions assessed the safety, perceptions, and discontinuation of treatment with TDB in a real-world, non-interventional setting (ClinicalTrials.gov study ID: NCT01225861). METHODS: Patients aged ≥18 years who were already receiving or initiating treatment with TDB were recruited in the UK during routine clinical visits and were followed for 6 visits or 9 months (whichever came first). Self-reported treatment adherence, patient satisfaction, and safety data were collected at each study visit. RESULTS: Of 465 patients, 272 were already receiving 7-day TDB at the study start (TDB experienced), 146 were TDB naïve, and 47 were prescribed twice-weekly TDB. Most patients were female (72.9 %) and overweight/obese (body mass index ≥25: 75.3 %). The median age was 67 years, and the mean duration of pain was 11.1 years. Arthritis/other musculoskeletal disorders (39.6 %) were the most common causes of pain. Mild adverse events were commonly reported. Skin irritations, which were most frequent in 7-day TDB-experienced patients (45.6 %), rarely resulted in treatment discontinuation (8.8 %). Nearly all patients used TDB in accordance with treatment recommendations. Most patients reported that TDB was 'effective'/'very effective' at relieving pain and were 'satisfied'/'very satisfied' with TDB therapy. CONCLUSION: In everyday clinical practice, TDB was well tolerated and patients were satisfied with their therapy. Self-reported adherence to TDB was very high, and adverse events rarely resulted in treatment discontinuation. Opportunities were identified to limit common adverse events associated with TDB.

Successful use of pregabalin by the rectal route to treat chronic neuropathic pain in a patient with complete intestinal failure.

Pregabalin is widely used for treatment of neuropathic pain and is only approved for oral use. This is the first reported case of using pregabalin by the rectal route for treatment in a 70-year-old patient with chronic neuropathic pain and complete intestinal failure. Therapies used in an attempt to manage his chronic pain have included a variety of doses and strengths of opioid preparations and cannabinoids, plus topical and alternative therapies. These were not effective, so it was decided to start a trial of pregabalin administered by the rectal route. Serum levels were measured to assess absorption. Within a few weeks of starting the treatment, the patient had improved pain control and appeared more comfortable and calm.

Successful use of stellate ganglion block and a new centrally acting analgesic with dual mode of action in a resistant temporomandibular joint pain.

Stellate ganglion blocks have been shown to provide effective pain relief in a number of different conditions involving the upper body. This was demonstrated in a 65-year-old woman who had experienced severe debilitating pain in her left temporomandibular joint (TMJ) and the surrounding area of her face for over 10 years. The pain was unresponsive to indomethacin, carbamazepine, sodium valproate, gabapentin, lithium, melatonin and amitriptyline. She had also had four surgical procedures to the TMJ without success. The pain was partially responsive to Syndol tablets and pregabalin, although the use of pregabalin was limited by its adverse effects. The patient underwent 13 ultrasound guided stellate ganglion blocks over a 24-month period which demonstrated 90% pain relief for up to 10 weeks. Pulsed radio frequency lesioning showed no benefit over stellate ganglion block. More recently, tapentadol was found to be effective and this replaced the stellate ganglion blocks.