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.

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.

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.

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.

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.

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.

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.

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.

Effects of tapentadol on pain, motor symptoms and cognitive functions in Parkinson's disease.

BACKGROUND: Pain is a common and undertreated non-motor symptom in patients with Parkinson's disease (PD). Opioids have been seldom used in PD because they could worsen cognitive and motor functions. OBJECTIVE: We aimed to assess efficacy and tolerability of tapentadol in PD patients. METHODS: We retrospectively reviewed 21 PD patients treated with tapentadol extended release (ER) for chronic pain. Patients were evaluated before treatment and at 3 and 6 months during treatment for pain intensity (current, 24-hour average, and minimum and worst) with a 0-10 Numerical Rating Scale and the painDETECT questionnaire; for motor symptom severity with the Unified PD Rating Scale part III and the Hoehn and Yahr scale; for cognitive functions with Mini-Mental Status Examination, Corsi's Block-Tapping test, Digit Span test, Digit-Symbol Substitution test, FAS test, Rey's Auditory Verbal Learning test, Trail-Making test A and B and the 9-Hole Peg test; for anxiety and depression with the Hospital Anxiety and Depression Scale; and for the quality of life with the Short Form-12. Data were analyzed by 1-way analysis of variance and paired t-test, and by Friedman's and Wilcoxon's tests. Statistical significance was taken in all cases as P<0.05. RESULTS: Pain intensity decreased over the course of treatment. No differences were found in PD symptom severity and dopaminergic drug dosages between pretreatment and treatment evaluations. No decrement in cognitive neuropsychological performances was found and an improvement was observed in Digit Span test, Digit-Symbol Substitution test, and FAS test. The levels of anxiety, depression, and quality of life improved. Overall, tapentadol ER was well tolerated and most patients reported no or mild and short-lived gastroenterological and neurological side effects. CONCLUSION: These results indicate the potential efficacy and tolerability of medium-high doses of tapentadol ER for the treatment of pain in PD.

Lidocaine 5% medicated plaster for localized neuropathic pain in thoracic surgical patients.

CONTEXT: Neuropathic pain is a common and distressing symptom in thoracic surgical patients. When it consistently presents with measurable sensory changes in a circumscribed area, neuropathic pain can be diagnosed as localized neuropathic pain (LNP). OBJECTIVE: The purpose of this study was to report the efficacy of lidocaine 5% medicated plaster (Lido5%P) in the treatment of LNP in thoracic surgical patients. METHODS: We retrospectively reviewed the records of sixteen cancer and noncancer thoracic patients treated with Lido5%P for LNP. Patients had been assessed before and during treatment with standardized forms and questionnaires for pain intensity, sleep quality, drug dosages and adverse events. RESULTS: Treatment with Lido5%P yielded a significant and lasting improvement in pain symptomatology. In oncological patients as an add-on therapy, Lido5%P improved pain intensity and sleep quality, and delayed opioid dose escalation. In non-oncological patients as monotherapy or in association with antineuropathic drugs, Lido5%P attenuated LNP. No local or systemic adverse events were recorded. CONCLUSIONS: Lido5%P was effective in relieving thoracic LNP, and was well tolerated.

Lidocaine 5% Medicated Plaster for Spinal Neuropathic Pain.

Spinal cord injuries frequently determine central pain symptoms that are difficult to control. The authors present the case of a 67-year-old suffering from a pleural mesothelioma. During the disease course, he developed a paraplegia syndrome from mesothelioma compression of the spinal cord at T4-T5 level. Following spinal decompression surgery, the patient presented an intense at-level, superficial neuropathic pain syndrome with allodynia and hyperalgesia. After systemic pharmacological therapies had failed, treatment with lidocaine 5% plaster was initiated. The superficial neuropathic symptoms almost completely disappeared within a few days. The lidocaine topical treatment was continued for months with durable analgesic effect.

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.

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.

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.