Cannabinoid levels description in a cohort of patients with chronic and neuropathic pain treated with Cannabis decoction: A possible role of TDM.

The phytocomplex of Cannabis is made up of approximately 500 substances: terpeno-phenols metabolites, including Δ-9-tetrahydrocannabinol and cannabidiol, exhibit pharmacological activity. Medical Cannabis has several pharmacological potential applications, in particular in the management of chronic and neuropathic pain. In the literature, a few data are available concerning cannabis pharmacokinetics, efficacy and safety. Thus, aim of the present study was the evaluation of cannabinoid pharmacokinetics in a cohort of patients, with chronic and neuropathic pain, treated with inhaled medical cannabis and decoction, as a galenic preparation. In this study, 67 patients were enrolled. Dried flower tops with different THC and CBD concentrations were used: Bedrocan® medical cannabis with THC level standardized at 19% and with a CBD level below 1%, Bediol® medical cannabis with THC and CBD level standardized at similar concentration of 6.5% and 8%, respectively. Cannabis was administered as a decoction in 47 patients and inhaled in 11 patients. The blood withdrawn was obtained before the new dose administration at the steady state and metabolites plasma concentrations were measured with an UHPLC-MS/MS method. Statistically significant differences were found in cannabinoids plasma exposure between inhaled and oral administration of medical cannabis, between male and female and cigarette smokers. For the first time, differences in cannabinoid metabolites exposures between different galenic formulations were suggested in patients. Therapeutic drug monitoring could be useful to allow for dose adjustment, but further studies in larger cohorts of patients are required in order to confirm these data.

The relationship between alexithymia, sensory phenotype and neurophysiological parameters in patients with chronic upper limb neuropathy.

In this study, we investigated the relationship between sensory abnormalities evaluated by quantitative sensory testing (QST) and alexithymia, depression and anxiety in patients with neuropathic pain involving the upper limbs. We enrolled 62 patients (34 with carpal tunnel syndrome, 7 with brachial plexopathy, 3 with cervical painful radiculopathy, 5 with ulnar entrapment neuropathy at elbow and 13 with post-burn hypertrophic scars) and 48 healthy controls. All underwent nerve conduction studies (NCS), evaluation of cold, heat pain and vibration detection threshold (VDT) by QST and evaluation of alexithymia by Toronto Alexithymia Scale (TAS-20), depression by Beck Depression Inventory II (BDI-II), anxiety by State-Trait Anxiety Inventory (STAI-Y), level of psychological distress by 12-item General Health Questionnaire (GHQ-12) and perceived social support by the Multidimensional Scale of Perceived Social Support (MSPSS). The general linear model analysis revealed a significant relationship between TAS-20 overall and TAS-20 sub-score for difficulty identifying feelings and VDT z-scores in the left index with no interaction by year of education and sensory NCS results. Our results demonstrated the association between impairment of vibratory sensation of the left hand, reflecting cutaneous mechanoceptor dysfunction, and alexithymia, particularly the difficulty to identify feelings. The importance of delivering to patients with neuropathic pain personalized care that takes into account not only the neurophysiological aspects but also the aspects of mental functioning is discussed.

Peripheral Nerve Stimulation in the Treatment of Chronic Pain Syndromes From Nerve Injury: A Multicenter Observational Study.

INTRODUCTION: Assessing the feasibility, technical implications, and clinical benefits of peripheral nerve stimulation (PNS) performed by an implantable pulse generator (IPG) located close to the stimulation site. MATERIALS AND METHODS: Selected patients were affected by neuropathic pain associated with a documented peripheral nerve lesion, refractory to conventional surgical or pharmacological treatment. A PNS system specifically designed for peripheral placement (Neurimpulse, Padova, Italy) was implanted and followed for six months, recording the degree of patient's satisfaction (PGI-I questionnaire), the pain numerical rating scale (NRS) and the quality of life (SF36 questionnaire), as well as any change in drug regimen and work capability. The statistical significance of differences was determined by the paired Student's t-test. RESULTS: A total of 58 patients were referred to permanent IPG implantation. Stimulation failure due to lead damage or dislocation was noticed in two cases (3.4%) in six months. At the follow-up end, the relative NRS reduction averaged -58 ± 30% (p < 10-6 ) and was greater than 50% in 69% of the cases. Quality-of-life physical and mental indices were increased by 18% (p < 0.005) and 29% (p < 0.0005), respectively. The administration of antalgic drugs was stopped in 55% and reduced in 16% of the patients. Low-energy stimulation was possible in most cases, resulting in an IPG estimated life of 80 ± 35 months. CONCLUSIONS: Successful PNS was achieved with a stimulation system designed for peripheral location. This new technology reduced the incidence of lead-related adverse events and the energy cost of the treatment.

Analgo-sedation of patients with burns outside the operating room.

Following the initial resuscitation of burn patients, the pain experienced may be divided into a 'background' pain and a 'breakthrough' pain associated with painful procedures. While background pain may be treated with intravenous opioids via continuous infusion or patient-controlled analgesia (PCA) and/or less potent oral opioids, breakthrough pain may be treated with a variety of interventions. The aim is to reduce patient anxiety, improve analgesia and ensure immobilization when required. Untreated pain and improper sedation may result in psychological distress such as post-traumatic stress disorder, major depression or delirium. This review summarizes recent developments and current techniques in sedation and analgesia in non-intubated adult burn patients during painful procedures performed outside the operating room (e.g. staple removal, wound-dressing, bathing). Current techniques of sedation and analgesia include different approaches, from a slight increase in background pain therapy (e.g. morphine PCA) to PCA with rapid-onset opioids, to multimodal drug combinations, nitrous oxide, regional blocks, or non-pharmacological approaches such as hypnosis and virtual reality. The most reliable way to administer drugs is intravenously. Fast-acting opioids can be combined with ketamine, propofol or benzodiazepines. Adjuvant drugs such as clonidine or NSAIDs and paracetamol (acetaminophen) have also been used. Patients receiving ketamine will usually maintain spontaneous breathing. This is an important feature in patients who are continuously turned during wound dressing procedures and where analgo-sedation is often performed by practitioners who are not specialists in anaesthesiology. Drugs are given in small boluses or by patient-controlled sedation, which is titrated to effect, according to sedation and pain scales. Patient-controlled infusion with propofol has also been used. However, we must bear in mind that burn patients often show an altered pharmacokinetic and pharmacodynamic response to drugs as a result of altered haemodynamics, protein binding and/or increased extracellular fluid volume, and possible changes in glomerular filtration. Because sedation and analgesia can range from minimal sedation (anxiolysis) to general anaesthesia, sedative and analgesic agents should always be administered by designated trained practitioners and not by the person performing the procedure. At least one individual who is capable of establishing a patent airway and positive pressure ventilation, as well as someone who can call for additional assistance, should always be present whenever analgo-sedation is administered. Oxygen should be routinely delivered during sedation. Blood pressure and continuous ECG monitoring should be carried out whenever possible, even if a patient is undergoing bathing or other procedures that may limit monitoring of vital pulse-oximetry parameters.