Musculoskeletal pain conditions are age-related, leading contributors to chronic pain and pain-related disability, which are expected to rise with the rapid global population aging. Current medical ...treatments provide only partial relief. Furthermore, non-steroidal anti-inflammatory drugs (NSAIDs) and opioids are effective in young and otherwise healthy individuals but are often contraindicated in elderly and frail patients. As a result of its favorable safety and tolerability record, paracetamol has long been the most common drug for treating pain. Strikingly, recent reports questioned its therapeutic value and safety. This review aims to present guideline recommendations. Paracetamol has been assessed in different conditions and demonstrated therapeutic efficacy on both acute and chronic pain. It is active as a single agent and is additive or synergistic with NSAIDs and opioids, improving their efficacy and safety. However, a lack of significant efficacy and hepatic toxicity have also been reported. Fast dissolving formulations of paracetamol provide superior and more extended pain relief that is similar to intravenous paracetamol. A dose reduction is recommended in patients with liver disease or malnourished. Genotyping may improve efficacy and safety. Within the current trend toward the minimization of opioid analgesia, it is consistently included in multimodal, non-opioid, or opioid-sparing therapies. Paracetamol is being recommended by guidelines as a first or second-line drug for acute pain and chronic pain, especially for patients with limited therapeutic options and for the elderly.
Pain and depression are leading causes of disability and of profound social and economic burden. Their impact is aggravated by their chronicity and comorbidity and the insufficient efficacy of ...current treatments. Morphological and functional metabolism studies link chronic pain and depressive disorders to dysfunctional neuroplastic changes in fronto-limbic brain regions that control emotional responses to painful injuries and stressful events. Glutamate modulators are emerging new therapies targeting dysfunctional brain areas implicated in the generation and maintenance of chronic pain and depression. Here, we report the effects of two clinically approved glutamate modulators: acetyl-
L
-carnitine (ALCAR) and S, R(±)ketamine (KET). ALCAR is a natural neurotrophic compound currently marketed for the treatment of neuropathies. KET is the prototypical non-competitive antagonist at
N
-methyl-
D
-aspartate glutamate receptors and a clinically approved anesthetic. Although they differ in pharmacological profiles, ALCAR and KET both modulate aminergic and glutamatergic neurotransmissions and pain and mood. We assessed in rats the effects of ALCAR and KET on cerebral metabolic rates for glucose (rCMRglc) and assessed clinically the effects of ALCAR in chronic pain and of KET in post-operative pain. ALCAR and KET increased rCMRglc at similar degrees in prefrontal, somatosensory, and cingulate cortices, and KET increased rCMRglc at a different, much larger, degree in limbic and dopaminergic areas. While rCMRglc increases in prefrontal cortical areas have been associated with analgesic and antidepressant effects of ALCAR and KET, the marked metabolic increases KET induces in limbic and dopaminergic areas have been related to its psychotomimetic and abuse properties. In patients with chronic neuropathic pain, ALCAR (1,000 mg/day) yielded to a fast (2 weeks) improvement of mood and then of pain and quality of life. In day-surgery patients, KET improved dischargeability and satisfaction. In obese patients undergoing bariatric surgery, a single, low dose of KET (0.5 mg/kg) at induction of anesthesia determined a very fast (hours) amelioration of post-operative depression and pain and an opioid-sparing effect. These findings indicate that ALCAR and KET, two non-selective glutamate modulators, still offer viable therapeutic options in comorbid pain and depression.
Background
Chronic low back pain (CLBP) is a highly prevalent and disabling condition in the elderly, and yet it is undertreated and understudied in this patient population. Tapentadol is a central ...analgesic with an improved tolerability profile that may be particularly beneficial to the elderly CLBP.
Methods
We performed an observational retrospective study to comparatively assess the efficacy and tolerability of tapentadol in young and elderly patients with severe CLBP. Sixtyfive young patients (< 65 years) and 87 elderly patients (≥ 65 years) were titrated on tapentadol extended release to their optimal dose (25–250 mg bid) over 1 month and, then, maintained at that dose for 3 months. The primary endpoint were changes from baseline in 24-h pain intensity on a 0–10 Numerical Rating Scale (NRS) at month-4 of treatment (titration plus maintenance periods). Patients were assessed for several efficacy and tolerability outcomes using a battery of scales and tests for neuropathic pain intensity, quality of life and sleep, and cognitive and gastrointestinal functions.
Results
At pretreatment, young and elderly patients had similar pain intensities with younger patients presenting with more intense depressive and neuropathic pain symptoms, and lesser comorbidities and durations of pain (
P
< 0.05). Thirty-eight patients discontinued treatment because of adverse events occurring mostly during titration. Treatment with tapentadol was associated with comparable and clinically meaningful pain reductions in 24-h NRS from baseline to treatment month-4 both in young and elderly patients (− 5.3 ± 1.4 and – 4.8 ± 2.1;
P
< 0.01); a 50% pain relief was achieved in 66% and 58% of young and elderly patients. The percentage of patients with a neuropathic component decreased similarly in young and elderly patients (from 38 to 0% and from 19 to 3%;
P
< 0.01). Quality of life and sleep improved. The performances in global cognition and sustained attention tasks remained stable or improved across all age group.
Conclusions
These findings indicate that tapentadol extended release maintains efficacy and good tolerability in CLBP patients with advancing age.
Physiologically, the activation of presynaptic CB1 attenuates large and small bowel muscle tone and inhibits GI motility, mainly by reducing the release of acetylcholine from enteric nerves and also ...by inhibiting all the components of the peristaltic reflex (Wright et al., 2005). ...CB1 activation, via the purinergic system, inhibits spontaneous ileal contractions and modulate the activity of vagal neurotransmission, reducing intestinal peristalsis (DiPatrizio, 2016). N-arachidonoylethanolamine (anandamide, AEA) and 2-arachidonoyl glycerol (2-AG) are the best characterized endocannabinoids; they are synthesized from membrane phospholipids on demand: AEA is synthesized by N-acyl-phosphatidylethanolamine phospholipase D (NAPE-PLD); and 2-AG by diacylglycerol lipase (DAGL), then they are released and induce a local response by activating CB1 and/or CB2 receptors (the latter being involved mainly in pathophysiological conditions) (Izzo and Camilleri, 2008). Subsequent to their activation, endocannabinoids are inactivated by reuptake from the degradative enzymes fatty acid amide hydrolase (FAAH), located in cells of the myenteric plexus and monoacylglycerol lipase (MAGL), present in the nerve cells and fibers throughout the muscle mucosal layers of the intestine (Di Marzo, 2006). The main role of ECS in the GI tract is controlling intestinal hyper-contractility. ...it modulates visceral sensations, intestinal inflammation and gut–brain communications, all functions that appear to be dysregulated in IBS.
Chronic pain is a common, pervasive, and often disabling medical condition that affects millions of people worldwide. According to the Global Burden of Disease survey, painful chronic conditions are ...causing the largest numbers of years lived with disability worldwide. In America, more than one in five adults experiences chronic pain. Erector spinae plane block is a novel regional anesthesia technique used to provide analgesia with multiple possible uses and a relatively low learning curve and complication rate. Here, we review the erector spinae plane block rationale, mechanism of action and possible complications, and discuss its potential use for chronic pain with possible future directions for research
Purpose
The aim of this study was to assess whether addition of epineural buprenorphine prolonged postoperative analgesia of middle interscalene brachial plexus block (MIB) with levobupivacaine.
...Methods
One hundred and fifty consenting adult patients, scheduled for shoulder arthroscopic surgery for a rotator cuff tear under MIB with 29.5 ml of 0.75 % levobupivacaine, were randomized to receive additionally either saline or intramuscular buprenorphine 0.15 mg or epineural buprenorphine 0.15 mg. Onset of sensory and motor blocks, duration of postoperative analgesia, and consumption of postoperative analgesics were compared among the groups.
Results
There were significant (
P
< 0.05) differences in the onset and the duration of the sensory block and in the duration of postoperative analgesia. Duration of both sensory block and postoperative analgesia was longer (
P
< 0.05) in patients who had received epineural buprenorphine (856.1 ± 215.2 and 1,049.7 ± 242.2 min) than in patients who had received intramuscular buprenorphine (693.6 ± 143.4 and 820.3 ± 335.3 min) or saline (488.3 ± 137.6 and 637.5 ± 72.1 min). Requirement of postoperative rescue analgesics was lower in the epineural buprenorphine group than in the other two groups. Few complications occurred from MIB (<1 %) and none from buprenorphine.
Conclusions
Epineural buprenorphine prolonged postoperative analgesia of MIB more effectively than intramuscular buprenorphine, which suggests that buprenorphine acts at a peripheral nervous system site of action.
The selective serotonin reuptake inhibitors (SSRI) exert a wide range of neurochemical and therapeutic activities. To investigate the neural effectors of SSRIs, we measured the regional cerebral ...metabolic rates for glucose (rCMRglc) in 56 brain regions of Fischer-344 rats 30
min after intraperitoneal injection of 0.4, 4 or 40
mg/kg of fluoxetine or fluvoxamine or after 4
mg/kg of paroxetine or sertraline. Both shared and drug-specific effects were detected. While all four SSRIs similarly reduced rCMRglc in a network of subcortical brain regions including the amygdala, locus coeruleus, basal ganglia and hypothalamic paraventricular nuclei, fluvoxamine, paroxetine and sertraline reduced rCMRglc also in the hippocampus and sertraline in the lateral habenula. The topography and the relation to dose of rCMRglc reductions by SSRIs differ from those of other classes of antidepressants, thus suggesting that SSRIs may specifically modulate brain areas involved in the physiological responses to stress.
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