Pain And The Use Of Gabapentinoids In German Nursing Home Residents - Results From An Analysis Based On Statutory Health Insurance Data.

BACKGROUND: Gabapentinoids (gabapentin and pregabalin) are psychoactive medications that are increasingly used for different conditions. Since there is evidence that psychotropic drugs, in general, are often inappropriately prescribed in elderly patients, we aimed to determine frequency and indications of gabapentinoid prescribing for nursing home residents. METHODS: We analyzed data from a large German statutory health insurance database. Included were records from people ≥65 years-of-age, who were admitted to a nursing home between January 2010 and December 2014. We determined the number and proportion of common indications for on- and off-label prescriptions, the most frequent co-medications, and the characteristics of patients and prescribers. RESULTS: Of 127,277 residents, 9539 (7.5%) received gabapentinoids and 4852 initiated treatment (4.0%; with 66.3% pregabalin). Median age of gabapentinoid initiators was 84 years (78.5% females). In these users, on-label prescribing was found in 57.4%, predominantly for neuropathic pain. Other painful conditions were also chief causes (84.7%) for off-label prescribing. Gabapentinoids were mainly started by general practitioners (64.5%) while pain specialists contributed <2%. Forty-six percent of users received additional opioids and in 27.5% gabapentinoids were prescribed only once. CONCLUSION: Gabapentinoids were frequently used in nursing home residents. Regular co-prescribing with opioids and psychotropic drugs might indicate employment to improve pain or assist treatment of conditions that are frequently associated with disruptive behavior such as dementia. However, more research is needed to better understand decision-making regarding gabapentinoid prescribing, especially in view of aggressive marketing, uncertain analgesic effects, problematic side effects, and uncritical use in the elderly.

Pain Assessment in INTensive care (PAINT): an observational study of physician-documented pain assessment in 45 intensive care units in the United Kingdom.

Pain is a common and distressing symptom experienced by intensive care patients. Assessing pain in this environment is challenging, and published guidelines have been inconsistently implemented. The Pain Assessment in INTensive care (PAINT) study aimed to evaluate the frequency and type of physician pain assessments with respect to published guidelines. This observational service evaluation considered all pain and analgesia-related entries in patients' records over a 24-h period, in 45 adult intensive care units (ICUs) in London and the South-East of England. Data were collected from 750 patients, reflecting the practice of 362 physicians. Nearly two-thirds of patients (n = 475, 64.5%, 95%CI 60.9-67.8%) received no physician-documented pain assessment during the 24-h study period. Just under one-third (n = 215, 28.6%, 95%CI 25.5-32.0%) received no nursing-documented pain assessment, and over one-fifth (n = 159, 21.2%, 95%CI 19.2-23.4)% received neither a doctor nor a nursing pain assessment. Two of the 45 ICUs used validated behavioural pain assessment tools. The likelihood of receiving a physician pain assessment was affected by the following factors: the number of nursing assessments performed; whether the patient was admitted as a surgical patient; the presence of tracheal tube or tracheostomy; and the length of stay in ICU. Physician-documented pain assessments in the majority of participating ICUs were infrequent and did not utilise recommended behavioural pain assessment tools. Further research to identify factors influencing physician pain assessment behaviour in ICU, such as human factors or cultural attitudes, is urgently needed.

[Piritramide : A critical review]. / Piritramid : Eine kritische Übersicht.

BACKGROUND: In many European countries and particularly in Germany, piritramide is the first choice opioid analgesic for the management of postoperative and posttraumatic pain. OBJECTIVE: The aim of this study was to review the pharmacological properties of piritramide and to evaluate whether these result in any clinical advantages with respect to effectiveness, safety and side effect profile compared to other strong opioids. MATERIAL AND METHODS: A systematic literature search was conducted in PubMed and Google Scholar and 27 articles published between 1961 and 2015 were retrieved and included in this review. RESULTS: Piritramide is a strong opioid that can only be administered parenterally. After intravenous injection it is effective after 17 min with pain relief lasting for up to 6 h. It is metabolized in the liver to inactive compounds, which is advantageous compared to morphine where active metabolites can accumulate in patients with renal failure. Piritramide is highly lipophilic resulting in a long context-sensitive half-life, making it unsuitable for continuous infusions. Studies further suggest that the side effect profile of piritramide is comparable to morphine. CONCLUSION: So far there is little evidence to support the widespread use of piritramide as first-line opioid analgesic for postoperative pain management in Germany. Especially lacking are in-depth studies about its mechanisms of action, receptor pharmacology, dose-response relationships and clinical dosing regimens. It is therefore questionable why piritramide is given priority.

Assessing pain objectively: the use of physiological markers.

Pain diagnosis and management would benefit from the development of objective markers of nociception and pain. Current research addressing this issue has focused on five main strategies, each with its own advantages and disadvantages. These encompass: (i) monitoring changes in the autonomic nervous system; (ii) biopotentials; (iii) neuroimaging; (iv) biological (bio-) markers; and (v) composite algorithms. Although each strategy has shown areas of promise, there are currently no validated objective markers of nociception or pain that can be recommended for clinical use. This article introduces the most important developments in the field and highlights shortcomings, with the aim of allowing the reader to make informed decisions about what trends to watch in the future.

Is number sense impaired in chronic pain patients?

BACKGROUND: Recent advances in imaging have improved our understanding of the role of the brain in painful conditions. Discoveries of morphological changes have been made in patients with chronic pain, with little known about the functional consequences when they occur in areas associated with 'number-sense'; thus, it can be hypothesized that chronic pain impairs this sense. METHODS: First, an audit of the use of numbers in gold-standard pain assessment tools in patients with acute and chronic pain was undertaken. Secondly, experiments were conducted with patients with acute and chronic pain and healthy controls. Participants marked positions of numbers on lines (number marking), before naming numbers on pre-marked lines (number naming). Finally, subjects bisected lines flanked with '2' and '9'. Deviations from expected responses were determined for each experiment. RESULTS: Four hundred and ninety-four patients were audited; numeric scores in the 'moderate' and 'severe' pain categories were significantly higher in chronic compared with acute pain patients. In experiments (n=150), more than one-third of chronic pain patients compared with 1/10th of controls showed greater deviations from the expected in number marking and naming indicating impaired number sense. Line bisection experiments suggest prefrontal and parietal cortical dysfunction as cause of this impairment. CONCLUSIONS: Audit data suggest patients with chronic pain interpret numbers differently from acute pain sufferers. Support is gained by experiments indicating impaired number sense in one-third of chronic pain patients. These results cast doubts on the appropriateness of the use of visual analogue and numeric rating scales in chronic pain in clinics and research.

An obligatory role for spinal cholinergic neurons in the antiallodynic effects of clonidine after peripheral nerve injury.

BACKGROUND: Indirect evidence supports a role of spinal cholinergic neurons in tonically reducing response to noxious mechanical stimulation and in effecting analgesia from alpha2-adrenergic agonists. This study directly assessed the role of cholinergic neurons in regulating the level of mechanical allodynia and in participating in the antiallodynic effect of the clinically used alpha2-adrenergic agonist, clonidine, in an animal model of neuropathic pain. METHODS: Allodynia was produced in rats by ligation of the left L5 and L6 spinal nerves. Rats received a single intrathecal injection of saline or one of three different doses of the cholinergic neurotoxin, ethylcholine mustard aziridinium ion (AF64-A; 2, 5, and 15 nmol). Seven days later, allodynia was assessed before and after intrathecal injection of 15 microg clonidine. The spinal cord was removed, and spinal cord acetylcholine content, cholinergic neuron number and distribution, and alpha2-adrenergic receptor expression were determined. RESULTS: AF64-A administration reduced both the number of cholinergic cells and the acetylcholine content of the lumbar dorsal spinal cord by 20-50% but did not affect level of mechanical allodynia. AF64-A did, however, completely block the anti-allodynic effect of clonidine. AF64-A did not reduce alpha2-adrenergic ligand binding in dorsal lumbar cord. CONCLUSIONS: These data suggest that spinal cholinergic tone does not affect the level of mechanical allodynia after peripheral nerve injury. There is a quantitative reliance on spinal cholinergic neurons in the allodynia relieving properties of intrathecal clonidine, and this reliance does not depend on alpha2-adrenergic receptors colocalized on spinal cholinergic interneurons.

Functional reorganization of the human primary somatosensory cortex after acute pain demonstrated by magnetoencephalography.

The somatosensory system is capable of functional reorganization following peripheral denervation or training. Studies on human amputees with phantom limb pain provided evidence that these reorganizational changes are modulated through nociceptive input. In the present study we used magnetoencephalographic recordings of six healthy volunteers to assess whether acute pain by itself causes a reorganization of the primary somatosensory cortex. After the induction of an intense experimental pain at the thenar of the left hand by intradermal injection of capsaicin, the extent of the cortical hand representation and the distance between the hand representation and the localization of the lip decreased. A likely mechanism for this acute reorganization is that pain induced hyperresponsiveness of the left thenar to tactile input from neighboring body sites.

Experimental arthritis in the rat does not alter the analgesic potency of intrathecal or intraarticular morphine.

UNLABELLED: To explore further the role of inflammatory processing on peripheral opioid pharmacology, we examined whether the potency of intraarticular (i.a.) or intrathecal (i.t) morphine in tests of thermal and mechanical nociception changed during the induction of experimental arthritis in the rat. Thermal nociception by i.t. morphine (3, 10, and 50 micrograms) or i.a. morphine (100, 1000, and 3000 micrograms) was assessed by means of a modified Hargreaves box ever) 28 h. Mechanical antinociception was determined for the largest applied doses of morphine using von Frey hairs. Morphine produced dose-dependent thermal antinociception after i.t. or i.a. administration: a 50% increase in maximum antinociceptive thermal response (50% effective dose) was produced by i.t. doses of 9.7 micrograms at the start and 9.1 micrograms at the end of this 28-h observational interval, whereas after i.a. administration, 50% effective dose values were 553 micrograms at the start and 660 micrograms at the end. The largest applied dose of either i.t. or i.a. morphine produced mechanical antinociception. On Day 1, the antinociceptive effect for mechanical nociception (expressed as the area under the curve of the percentage of maximal possible effect values at 0.5, 1, 2, and 4 h) was 68% for i.t. morphine 50 micrograms and 53% for i.a. morphine 3000 micrograms. Neither result differed from the corresponding area under the curve values on Day 2. Naloxone administered either i.t. or i.a. abolished the antinociceptive action of morphine given at the same site. We conclude that, although morphine has a peripheral analgesic site of action in a rat arthritis model, its potency for both i.a. and i.t. routes of administration does not change during the onset of arthritis. IMPLICATIONS: In this animal study, we showed that the administration of morphine modulates thermal and mechanical antinociception at central and peripheral sites in inflammatory pain.

Thermal and mechanical antinociceptive action of spinal vs peripherally administered clonidine in the rat inflamed knee joint model.

It has been demonstrated recently that in addition to its spinal analgesic actions, the alpha 2 adrenoreceptor agonist clonidine also has peripheral analgesic activity. Few data are available regarding the antinociceptive effects of spinal vs peripherally delivered clonidine in inflammatory pain. Thus we have studied spinal (intrathecal = i.t.) and peripheral (intra-articular = i.a.) administration of clonidine in the rat inflamed knee joint model. Thermal and mechanical antinociception was assessed in rats over 28 h using a modified Hargreaves box and von Frey hairs after induction of tonic persistent inflammatory pain by injection of a kaolin-carrageenan mixture into the right knee joint. Thirty minutes after injection of kaolin-carrageenan, clonidine was administered via an i.t. catheter or by i.a. injection into the right inflamed knee joint or by subcutaneous injection (s.c.) (highest effective intra-articular dose). The specific site of action was assessed using the alpha 2 antagonist yohimbine i.t., i.a. or s.c. Clonidine i.t. resulted in thermal and mechanical antinociception during ongoing inflammation, which was not enhanced by inflammation. In contrast, i.a. delivery of clonidine, which also produced a dose-dependent thermal and mechanical antinociceptive effect, revealed a leftward shift in the antinociceptive activity produced by ongoing inflammation. Yohimbine inhibited the antinociceptive action of clonidine at the site of delivery. We suggest that clonidine produces potent thermal and mechanical antinociception regardless of the route of administration. However, chronic inflammatory processing appears to enhance the antinociceptive efficacy of the peripheral alpha 2 agonist.

Ascorbic acid reduces the endotoxin-induced lung injury in awake sheep.

Our aim was to investigate whether ascorbic acid can reduce reactive oxygen metabolite-mediated acute lung injury. The effects of intravenous administration of Escherichia coli endotoxin were studied, with and without ascorbic acid infusion, on haemodynamics, lung lymph flow, cardio-respiratory and neutrophil function in chronically instrumented sheep. Paired experiments were performed on eight sheep in which they received either endotoxin alone (0.5 micrograms kg-1 b.w.) (ET group) or in combination with an ascorbic acid infusion (1 g kg-1 b.w. bolus injection followed by 0.2 g kg-1 h-1 continuous infusion) ET + ASC group) in random order. Four of the animals also received ascorbic acid alone (ASC group). As a result, for the ET + ASC group a general and mostly significant improvement (P < 0.05) in the early hypertensive phase (0-60 min, P values) and in the late permeability phase (2-4 h, *P values) of cardiorespiratory function (mean artery pressure: P/*P = 0.283/0.049; mean pulmonary artery pressure: P/*P = 0.0001/0.0001; mean pulmonary artery wedge pressure: P/*P = 0.012/0.001; right ventricular stroke work index: P/*P = 0.02/0.0001; cardiac index: P/*P = 0.797/0.755; arterial oxygen saturation: P/*P = 0.0059/0.01; arterial-venous difference of oxygen tension: P/*P = 0.011/0.0005), oxygen consumption: P/*P = 0.013/0.035, lung lymph flow: P/*P = 0.562/0.012, lymph/plasma protein ratio: P/*P = 0.304/0.008 and protein clearance: P/*P = 0.56/0.05 was observed in comparison with the ET group.(ABSTRACT TRUNCATED AT 250 WORDS)