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Intravenous lidocaine infusions have been shown to be effective for cancer related pain, but access is restricted to acute care settings. If able to be shown to be safe and effective, the subcutaneous route could expand access to residential hospices or patients' homes. This randomized, double-blind, placebo controlled, 2 × 2 crossover trial evaluated the effectiveness, safety, toxicity, and impact on quality of life of a limited duration subcutaneous lidocaine infusion (SCLI) for chronic cancer pain. Patients with the life expectancy of three months or more, who were experiencing cancer-related pain with a worst severity of at least 4 on a 0-10 scale despite a trial of at least one opioid and appropriate adjuvant analgesic, received two subcutaneous infusions at least a week apart; lidocaine 10 mg/kg over 5.5 hours and saline placebo. The primary outcome was either a reduction in worst pain intensity of two points out of 10 or a reduction in 24 hours opioid dose of at least 30% without worsening of pain scores, in seven days. The SCLI was only effective for two subjects. One of these subjects experienced a drop in worst pain score and the other experienced a reduction in opioid dose. A weight-based subcutaneous infusion of lidocaine does not achieve sufficiently predictable blood levels for determining lidocaine responsiveness. This study does not allow any conclusion to be drawn on whether or not lidocaine would have been more effective had it been titrated to higher blood levels.
Learn More >Maladaptive plasticity of neurons in lamina I of the spinal cord is a lynchpin for the development of chronic pain, and is critically dependent upon intracellular calcium signaling. However, the relationship between neuronal activity and intracellular calcium in these neurons is unknown. Here we combined two-photon calcium imaging with whole-cell electrophysiology to determine how action potential firing drives calcium responses within subcellular compartments of male rat spinal cord lamina I neurons. We found that single action potentials generated at the soma increase calcium concentration in the somatic cytosol and nucleus, and these calcium responses invade dendrites and dendritic spines by active backpropagation. Calcium responses in each compartment were dependent upon voltage-gated calcium channels, and somatic and nuclear calcium responses were amplified by release of calcium from ryanodine-sensitive intracellular stores. Grouping single action potential-evoked calcium responses by neuron type demonstrated their presence in all defined types, as well as a high degree of similarity in calcium responses between neuron types. With bursts of action potentials, we found that calcium responses have the capacity to encode action potential frequency and number in all compartments, with action potential number being preferentially encoded. Together, these findings indicate that intracellular calcium serves as a readout of neuronal activity within lamina I neurons, providing a unifying mechanism through which activity may regulate plasticity, including that seen in chronic pain.Despite their critical role in both acute pain sensation and chronic pain, little is known of the fundamental physiology of spinal cord lamina I neurons. This is especially the case with respect to calcium dynamics within these neurons, which could regulate maladaptive plasticity observed in chronic pain. By combining two-photon calcium imaging and patch-clamp electrophysiological recordings from lamina I neurons, we found that action potential firing induces calcium responses within the somatic cytosol, nucleus, dendrites, and dendritic spines of lamina I neurons. Our findings demonstrate the presence of actively backpropagating action potentials, shifting our understanding of how these neurons process information, such that calcium provides a mechanism for lamina I neurons to track their own activity.
Learn More >Background and aims There is very little published evaluation of the treatment of military veterans with chronic pain, with or without post-traumatic stress disorder. Few clinical services offer integrated treatment for veterans with chronic pain and PTSD. Such veterans experience difficulty in accessing treatment for either condition: services may consider each condition as a contraindication to treatment of the other. Veterans are therefore often passed from one specialist service to another without adequate treatment. The veteran pain management programme (PMP) in the UK was established to meet the needs of veterans suffering from chronic pain with or without PTSD; this is the first evaluation. Methods The PMP was advertised online via veteran charities. Veterans self-referred with accompanying information from General Practitioners. Veterans were then invited for an inter-disciplinary assessment and if appropriate invited onto the next PMP. Exclusion criteria included; current severe PTSD, severe depression with active suicidal ideation, moderate to severe personality disorder, or who were unable to self-care in the accommodation available. Treatment was by a team of experienced pain management clinicians: clinical psychologist, physiotherapist, nurse, medical consultant and psychiatrist. The PMP was delivered over 10 days: five residential days then five single days over the subsequent 6 months. The PMP combines cognitive behavioural treatment, which has the strongest evidence base, with more recent developments from mindfulness-based CBT for pain and compassion-focused therapy. Standard pain management strategies were adapted to meet the specific needs of the population, recognising the tendency to use demanding activity to manage post-traumatic stress symptoms. Domains of outcome were pain, mood, function, confidence and changes in medication use. Results One hundred and sixty four military veterans started treatment in 19 programmes, and 158 completed. Results from those with high and low PTSD were compared; overall improvements in all domains were statistically significant: mood, self-efficacy and confidence, and those with PTSD showed a reduction (4.3/24 points on the IES-6). At the end of the programme the data showed that 17% reduced opioid medication and 25% stopped all opioid use. Conclusions Veterans made clinically and statistically significant improvements, including those with co-existing PTSD, who also reduced their symptom level. This serves to demonstrate the feasibility of treating veterans with both chronic pain and PTSD using a PMP model of care. Implications Military veterans experiencing both chronic pain and PTSD can be treated in a PMP adapted for their specific needs by an experienced clinical team.
Learn More >Background and aims Patients usually receive a prescription for morphine or another opioid at discharge after surgery. Several studies have shown that many patients do not step down but develop persistent opioid use following surgery. The purpose of this study was to gain insight of patients' experiences with opioid tapering after surgery and to propose recommendations for clinicians to assist patients in opioid tapering. Methods Using a qualitative study design, 15 adult patients who took opioids before surgery and still had a daily consumption of opioids 6 months following spine surgery were interviewed. Results Analyses of the transcripts identified three major themes and eight subthemes. The major themes were as follows: (1) The patients' experienced that their whole life revolved around pain and opioids and felt stigmatized and suspected of being drug addicts by their social circle and health care professionals (2) Barriers for opioid tapering were increased pain, opioid dependency and fear of withdrawal symptoms (3) Motivational factors for opioid tapering were fear of dependency, the prospect of a better health, patient involvement in opioid tapering and a trusting relationship between patient and clinician. Conclusions The results of this study highlight that opioid tapering is challenging and may be influenced by many different factors. Some patients find opioid tapering particularly difficult and therefore need additional assistance in order to taper off successfully. Implications For opioid tapering to succeed, it is highly important to establish a trustful relationship with the patients, to take each patient's personal circumstances into account and to address fears of increased pain and withdrawal symptoms. Clinicians should also focus on patient involvement in opioid tapering and consider to offer a follow-up after discharge to patients at risk for prolonged opioid use.
Learn More >Mental, emotional, physical, and general fatigue, as well as vigor, have each been associated with pain interference-defined as pain-related disruption of social, recreational, and work-related activities-in patients with chronic orofacial pain (COFP). The objectives of the current study were to compare levels of these fatigue subtypes across younger, middle-aged, and older patients with COFP and test the associations between fatigue subtypes and pain interference in these age groups.
Learn More >Following amputation, nearly all amputees report non-painful phantom phenomena and many of them suffer from chronic phantom limb pain (PLP) and residual limb pain (RLP). The etiology of PLP remains elusive and there is an ongoing debate on the role of peripheral and central mechanisms. Few studies have examined the entire somatosensory pathway from the truncated nerves to the cortex in amputees with PLP compared to those without PLP. The relationship between afferent input, somatosensory responses and the change in PLP remains unclear.
Learn More >Differences in nociception and use of opioids between sexes are of particular interest, considering higher rates of persistent opioid use among women after surgery. Although enhanced recovery protocols (ERPs) have improved postoperative pain control in colorectal surgery, sex-based comparisons of inpatient opioid use after surgery in an ERP remain understudied.
Learn More >Areas of secondary hyperalgesia can be assessed using quantitative sensory testing (QST). Delivering noxious electrocutaneous stimulation could provide added benefit by allowing multiple measurements of the magnitude of hyperalgesia. We aimed to characterize the use of electrical pain perception (EPP) thresholds alongside QST as a means by which to measure changes in pain thresholds within an area of secondary mechanical hyperalgesia.
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