Efficacy and tolerability of tapentadol for the treatment of chronic low back pain in elderly patients.

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.

Long-Term Outcome and Predictors of Transversus Abdominis Plane Block for Chronic Post-Hernioplasty Pain.

Background/Objectives: Different analgesic techniques have been used in the clinical management of chronic post-hernioplasty pain (CPHP), with variable results. This study aimed to investigate clinical factors associated with long-term outcome of the transversus abdominal plane (TAP) block for CPHP. Methods: We retrospectively analyzed 26 patients with CPHP who were treated with single or multiple TAP blocks with local anesthetic and steroid. Patients were evaluated for pain and neuropathic pain intensity by a Numerical Rating Scale (NRS) and the painDETECT questionnaire (PDQ), for anxiety and depression by the Hospital Anxiety and Depression Scale, and for quality of life by the 12-item Short Form Health Survey (SF12). Results: At 6 months post-treatment, 20 patients (77%) presented substantial (>50%) or moderate (30-50%) CPHP relief and were considered responders. In responders, the 24-h average and maximum NRS pain significantly declined (p < 0.01) from 7.3 ± 1.3 to 2.6 ± 2.1 and from 8.8 ± 1.5 to 5.1 ± 2.0, and the neuropathic PDQ score from 9.1 ± 3.2 to 6.1 ± 1.3; the physical SF12 score improved from 36.5 ± 5.8 to 44.3 ± 7.5 (p < 0.01). Six patients failed to achieve a significant CPHP improvement and were considered non-responders. Non-responders presented a significantly (p < 0.05) longer CPHP, higher body mass index and neuropathic symptoms, and more frequent anxiety, depression, diabetes, and fibromyalgia. Conclusions: The TAP block with local anesthetic and steroid should be considered as a therapeutic option for CPHP. However, medical and psychiatric comorbidities negatively impact the TAP block effectiveness for CPHP.

Coexistence of neuropathic corneal pain, corneal nerve abnormalities, depression, and low quality of life.

PURPOSE: To evaluate the quality of life (QoL), mental health conditions and corneal morphology in neuropathic corneal pain (NCP) subjects without a significant ocular surface disease. METHODS: A composite questionnaire was administered to 228 consecutive subjects, assessing the pain intensity, duration, and quality using a modified version of the Self-Administered Leeds Assessment of Neuropathic Symptoms and Signs (S-LANSS) and Pain Detect (PD) questionnaires. Subjects diagnosed with possible central NCP and two sub-groups of patients diagnosed with peripheral ocular pain completed an additional battery of mental health questionnaires and were examined by In Vivo Confocal Microscopy (IVCM). RESULTS: Of the 76 subjects that reported chronic ocular pain (duration >1 month), 53 were classified with probable NCP. Nine subjects without signs that justify the pain and non-responding to topical anaesthesia, were considered affected by central NCP. In these patients, a significant negative correlation was found between the presence pain and the mental component of the QoL (R2 = 0.733), and a positive correlation between the severity of pain the presence post-traumatic stress disorder (R2 = 0.83) and depression (R2 = 0.93). Although neuromas and sprouting had higher frequency in the central NCP group compared the control groups, these differences was not statistically different. CONCLUSIONS: The assessment of ocular pain characteristics using multiple questionnaires and IVCM may help to recognize differences between nociceptive and neuropathic pain. An association between pain intensity and mental health condition may guide the therapeutical choices.

Ganglionic blockade alters behavioral and cerebral metabolic responses to corticotropin releasing factor in the rat.

Corticotropin releasing factor (CRF) has potent stimulating effects on behavior and cerebral metabolism. To investigate the role of altered peripheral autonomic function in central actions of CRF, we measured the effects of intracerebroventricular CRF (2 µg) on locomotor activity and regional cerebral metabolic rates for glucose (rCMRglc) in control, saline pretreated rats and in rats pretreated with the ganglionic receptor blocker hexamethonium bromide (HEX) (5 mg/kg). Locomotor activity was assessed in a familial environment with an activity meter. rCMRglc were measured in 74 brain regions with the quantitative autoradiographic [¹4C]2-deoxy-D-glucose technique. In control rats, CRF increased the spontaneous locomotor activity and rCMRglc in 14 sensorimotor, limbic, hypothalamic and brainstem regions. HEX pretreatment blunted locomotor activations induced by CRF. While HEX did not affect cerebral metabolic activation by CRF in sensorimotor areas, it reduced metabolic activations in hippocampal and hypothalamic regions and increased metabolic activations in the brainstem reticular formation. These data indicate that CRF increases rCMRglc in the sensorimotor areas by direct CNS activity and in the limbic areas by indirect, autonomically mediated, activity. Autonomic activation also accounts, at least in part, for the motor activating properties of CRF.

Erector Spinae Plane Block and Chronic Pain: An Updated Review and Possible Future Directions.

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.

Hemodynamic and hormonal stress responses to endotracheal tube and ProSeal Laryngeal Mask Airway™ for laparoscopic gastric banding.

BACKGROUND: The stress responses from tracheal intubation are potentially dangerous in patients with higher cardiovascular risk, such as obese patients. The primary outcome objective of this study was to test whether, in comparison with the endotracheal tube (ETT), the Proseal™ Laryngeal Mask Airway (PLMA™) (Laryngeal Mask Airway Company, Jersey, United Kingdom) reduces blood pressure and norepinephrine responses and the amounts of muscle relaxants needed in obese patients. METHODS: We assessed hemodynamic and hormonal stress responses, ventilation, and postoperative recovery in 75 morbidly obese patients randomized to receive standardized anesthesia with either an ETT or the PLMA™ for laparoscopic gastric banding. RESULTS: In repeated-measures ANOVA, mean arterial blood pressure and plasma norepinephrine were significantly higher in the ETT group than in the PLMA™ group. In individual pairwise comparisons, blood pressure rose higher in ETT than PLMA™ patients after insertion and removal of airway devices, and after recovery. In ETT compared with PLMA™ patients, plasma norepinephrine was higher after induction of carboperitoneum (mean ± SD, 534 ± 198 and 368 ± 147 and pg/ml, P = 0.001), after airway device removal (578 ± 285 and 329 ± 128 pg/ml, P < 0.0001), and after recovery in postanesthesia care unit (380 ± 167 and 262 ± 95 and pg/ml, P = 0.003). Compared with use of the ETT, the PLMA™ reduced cisatracurium requirement, oxygen desaturation, and time to discharge from both the postanesthesia care unit and the hospital. CONCLUSIONS: PLMA™ reduces stress responses and postoperative complaints after laparoscopic gastric banding.

Buprenorphine added to levobupivacaine enhances postoperative analgesia of middle interscalene brachial plexus block.

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.

Paracetamol for multimodal analgesia.

Pain and related disability remain a major social and therapeutic problem. Comorbidities and therapies increase drug interactions and side effects making pain management more compounded especially in the elderly who are the fastest-growing pain population. Multimodal analgesia consists of using two or more drugs and/or techniques that target different sites of pain, increasing the level of analgesia and decreasing adverse events from treatment. Paracetamol enhances multimodal analgesia in experimental and clinical pain states. Strong preclinical evidence supports that paracetamol has additive and synergistic interactions with anti-inflammatory, opioid and anti-neuropathic drugs in rodent models of nociceptive and neuropathic pain. Clinical studies in young and adult elderly patients confirm the utility of paracetamol in multimodal, non-opioid or opioid-sparing, therapies for the treatment of acute and chronic pain.

Opioid and anti-inflammatory drugs are essential medications to relief pain; however, they may pose a serious health risk especially in elderly patients and in patients with medical conditions. Doctors are studying ways to reduce or eliminate their use. We wanted to see how well paracetamol works together with other painkillers to manage pain. Paracetamol (or acetaminophen) is one of the most prescribed medication for fever and pain. We found strong evidence that paracetamol given in association with other analgesic drugs enhances the pain relief in adult patients and in elderly adult patients, even though more studies are warranted in the latter. The use of paracetamol in combination with other analgesics is recommended by physicians and surgeons of different specialties.

Analgesic and Antidepressant Effects of the Clinical Glutamate Modulators Acetyl-L-Carnitine and Ketamine.

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.

Paracetamol: A Review of Guideline Recommendations.

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.

Post-acute P300 predicts recovery of consciousness from traumatic vegetative state.

BACKGROUND: Evoked potentials allow one to assess functional integrity of sensory pathways projecting to primary sensory cortices and event-related potentials assess higher order cortical functions associated with stimulus detection and decision-making. Evoked and event-related potentials have been used to predict emergence from coma. This study aimed to determine whether they can help prediction of consciousness recovery in post-traumatic vegetative state (VS). METHODS: Thirty-four patients in post-traumatic VS were assessed clinically and neurophysiologically at 2-3 months after injury and followed up to 1 year. Patients were assessed with the Disability Rating Scale (DRS) and with electroencephalogram (EEG), brainstem auditory (BAEP) and somatosensory evoked potentials (SEP) and P300. Demographic, clinical and neurophysiological measures were analysed by descriptive and logistic regression techniques. RESULTS: At 1 year from injury, 26 patients (76%) had recovered consciousness and eight patients (24%) had not. In univariate analyses, a detectable P300, a reactive EEG and lower DRS scores were found at entry assessment more frequently (p < 0.05) in patients who later recovered consciousness than in those who did not. Logistic regression analysis revealed that P300 was the only factor contributing to prediction of conscious recovery with an area under the ROC curve of 0.94 (95% CI, 0.80-0.99). CONCLUSIONS: P300 is a strong predictor of conscious recovery in VS.

Bronchoscope-guided intubation through a Laryngeal Mask Airway Supreme in a patient with a difficult-to-manage airway.

We report a case of an obese patient who presented with laryngeal edema and difficult ventilation after failed attempts to intubate. A Laryngeal Mask Airway Supreme (LMA Supreme) reestablished the ventilation and allowed bronchoscope- guided intubation of the trachea. The case suggests that the LMA Supreme may be useful in patients with a difficult airway.

Tapentadol for neuropathic pain: a review of clinical studies.

Neuropathic pain (NP) is an enormous burden for patients, caregivers and society. NP is a pain state that may develop after injury of the peripheral or central nervous system because of a wide range of diseases and traumas. A NP symptom component can be found also in several types of chronic pain. Many NP patients are substantially disabled for years. Due to its chronicity, severity and unpredictability, NP is difficult to treat. Tapentadol is a central-acting oral analgesic with combined opioid and noradrenergic properties, which make it potentially suitable for a wide range of pain conditions, particularly whenever a NP component is present or cannot be excluded. In randomized controlled trials, tapentadol has proved to be effective in relieving NP in diabetic peripheral neuropathy and in chronic low back pain. In observational studies, tapentadol reduced NP in chemotherapy-induced peripheral neuropathies, blood and solid cancers, and the NP component in neck pain and Parkinson's disease. This narrative review aims to provide clinicians with a broad overview of tapentadol effects on NP.

Tapentadol: an effective option for the treatment of back pain.

Back pain, including low back pain and neck pain, is the leading cause of disability worldwide. This type of pain is challenging to treat, since it presents both a nociceptive and a neuropathic component. The latter also contributes to the evolution of pain toward chronification. Treatment selection should therefore consider the ability to prevent this event. Tapentadol is characterized by a unique and innovative peculiar mechanism of action that makes it the first representative of a new class of central strong analgesics referred to as MOR-NRI. This molecule acts both on the nociceptive and neuropathic components of pain, and it can therefore be effective in the treatment of a mixed pain condition such as back pain. This narrative review discusses the rationale for the use of tapentadol in both low back pain and neck pain and presents available clinical data. Overall, data show that tapentadol prolonged release is a well-grounded treatment for chronic back pain, sustained by a strong mechanistic rationale and robust evidence. Given also the availability of long-term efficacy and safety data, we believe that this molecule should be considered as an elective therapy for chronic back pain.

Cerebral metabolic effects of fluoxetine, fluvoxamine, paroxetine and sertraline in the conscious rat.

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.

The time-dependent effects of midazolam on regional cerebral glucose metabolism in rats.

BACKGROUND: Midazolam has hypnotic and sedative activities, which may be mediated by different neuronal structures. We investigated the time course effect of a hypnotic dose of midazolam on conscious motor behavior and on patterns of brain metabolism. METHODS: Loss of nociceptive reflexes and impairment of spontaneous locomotor activity were used as indices for the hypnotic and sedative effects of midazolam, and the regional cerebral metabolic rates for glucose (rCMRglc) were used as indices of neuronal effects of midazolam. Locomotor activity was measured with a monitor and rCMRglc were measured with the quantitative autoradiographic [(14)C]2-deoxyglucose procedure in 62 brain regions of Fischer-344 rats at 2, 30, 60, 120, and 180 min after i.v. administration of saline or midazolam 5 mg/kg. RESULTS: After midazolam administration, rats were anesthetized at 2 min, awake but severely impaired at 30 min and slowly recovering motor activity thereafter. Anesthesia was associated with widespread rCMRglc decreases (59 areas affected, 38% mean decrease). Recovery of consciousness was associated with normalizing rCMRglc in visual, auditory, and somatosensory cortices and in the locus coeruleus (47 regions affected, 31% decrease). Recovery of motor activity was paralleled by slow rCMRglc normalization in the frontal motor, limbic, and thalamic regions (at 60, 120, and 180 min 31, 17, 4 areas affected, 26, 20, and 15% decreases from control values). CONCLUSIONS: Whereas the hypnotic effects of midazolam may result from inhibition of brain structures involved in arousal and sensory processing, its sedative effects may result from inhibition of subcortical motor and limbic regions.