Search

The large inter-individual variability in the magnitude of analgesia in response to opioids and the high prevalence of adverse events associated with their use underline the clinical importance of being able to predict who will or will not respond to opioid treatment. The present study used both static and dynamic quantitative sensory testing (QST) on 40 healthy volunteers in order to test whether this methodology can predict the analgesic effects of oral oxycodone, as compared to a placebo, on latency to onset, pain intensity, and tolerance to the cold pressor test (CPT). Static QST consisted of measuring heat and cold pain thresholds. Dynamic QST included measurements of the magnitude of the diffuse noxious inhibitory control (DNIC)-like effect and of temporal summation (TS). Results showed that oxycodone, but not the placebo, significantly elevated the latency and tolerance to cold pain and significantly reduced pain intensity. The static QST results showed that heat pain thresholds predicted the magnitude of reduction in pain intensity in response to oxycodone treatment (F((1,22))=5.63, p=0.027, R(2)=0.17). The dynamic QST results showed that TS predicted the effect of oxycodone on the tolerance to CPT (F((1,38))=9.11, p=0.005, R(2)=0.17). These results suggest that both static and dynamic QST have the potential to be useful in the prediction of the response to opioid treatment., (Copyright © 2010 International Association for the Study of Pain. Published by Elsevier B.V. All rights reserved.)

Background: Chronic back and leg pain conditions result in patients' loss of function, reduced quality of life and increased costs to the society., Aims: To assess health-related quality of life (HRQoL) and cost implications of spinal cord stimulation plus non-surgical conventional medical management (SCS group) versus non-surgical conventional medical management alone (CMM group) in the management of neuropathic pain in patients with failed back surgery syndrome., Methods: A total of 100 patients were randomised to either the SCS or CMM group. Healthcare resource consumption data relating to screening, the use of the implantable generator in SCS patients, hospital stay, and drug and non-drug pain-related treatment were collected prospectively. Resource consumption was costed using UK and Canadian 2005-2006 national figures. HRQoL was assessed using the EuroQol-5D (EQ-5D) questionnaire. Costs and outcomes were assessed for each patient over their first 6-months of the trial., Results: The 6-month mean total healthcare cost in the SCS group (CAN$19,486; 12,653 euros) was significantly higher than in the CMM group (CAN$3994; 2594 euros), with a mean adjusted difference of CAN$15,395 (9997 euros) (p<0.001). However, the gain in HRQoL with SCS over the same period of time was markedly greater in the SCS group, with a mean EQ-5D score difference of 0.25 [p<0.001] and 0.21 [p<0.001], respectively at 3- and 6-months after adjusting for baseline variables., Conclusions: The addition of SCS to CMM in patients with neuropathic leg and back pain results in higher costs to health systems but also generates important improvements in patients' EQ-5D over the same period.

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed are tolerance to opioid side effects, use of botulinum toxin A in pain management, and the use of ketamine in pain management.

Complex regional pain syndrome is a painful disorder of unclear etiology, typically involving the distal part of one limb, represented by spontaneous and evoked pain as well as autonomic, motor and trophic abnormalities. It can be incapacitating and severely affect function and quality of life. Although full-blown complex regional pain syndrome can be diagnosed easily, less fulminate forms of the syndrome often remain undiagnosed. Controlled trials have demonstrated that a short course of oral corticosteroids, intranasal or intramuscular calcitonin, intravenous bisphosphonates, free-radical scavengers, gabapentin, regional intravenous sympathetic blocks with bretylium and spinal cord stimulation or physical therapy and occupational therapy can be efficacious for complex regional pain syndrome. Nonetheless, the management of this syndrome is difficult because currently available drugs and technologies do not provide adequate pain relief for a considerable percentage of sufferers. The present review focuses primarily on the pharmacotherapy of complex regional pain syndrome and describes briefly the epidemiology, pathogenesis and clinical manifestations of the syndrome.

Lamotrigine is an antiepileptic drug that stabilizes neural membranes by blocking the activation of voltage-sensitive sodium channels and inhibiting the presynaptic release of glutamate. Full length reports of five open trials and six out of seven randomized controlled trials (plus two abstracts) have demonstrated the efficacy of lamotrigine in the treatment of various forms of neuropathic pain. The present drug profile provides a review of the pharmacologic properties of lamotrigine, the clinical evidence related to its efficacy and safety, and discusses the current and future role of the drug in the treatment of neuropathic pain.

An open trial was conducted to study the potential efficacy of the antiepileptic agent lamotrigine in relieving the sciatic pain and the relationship between lamotrigine dosage, plasma concentration and the clinical response. Subsequent to a 1 week washout period from previous analgesics, lamotrigine dose was titrated on a weekly basis from 25 to 400mg/day and was maintained at that dose for additional 4 weeks. Spontaneous pain, the Short Form McGill Pain Questionnaire (SFMPQ), the Straight Leg Raise (SLR) test, and range of motion of the lumbar spine (leaning foreword, to the affected side) were used to assess lamotrigine efficacy. Lamotrigine plasma concentration was tested at the end of each week during the titration period and at the end of the study. Fourteen patients were enrolled in the study. All outcome measurers improved compared to baseline during the titration period, but reached a statistically significant level of improvement only at the 400mg dose. A linear correlation was found between mean lamotrigine dose, mean plasma concentration and mean weekly spontaneous pain, mean SLR and mean bending the affected side, but not with the SFMPQ score. Study results suggest lamotrigine is a potentially effective and safe compound for the treatment of painful lumbar radiculopathy, and that it is likely to act in a dose- and plasma concentration-dependent fashion.

Recent studies have provided evidence that excitatory amino acid antagonists can exert analgesic effects in animals. These studies, however, have focused primarily on phasic pain or hyperalgesia rather than tonic pain. The present study evaluates the effects of systemic administration of Memantine (1-amino-3,5-dimethyl-adamantane), a clinically used N-methyl-D-aspartate (NMDA) receptor antagonist, on formalin-induced phasic and tonic pain behavior in the rat. Memantine (2.5, 5.0, 10.0 and 20.0 mg/kg) or normal saline was injected i.p. 1 h prior to a s.c. injection of formalin (5%, 50 microliters) into the vibrissal pad of adult rats (n = 5/group). Pain behavior was measured by the number of seconds of formalin-induced face grooming during a 42-min post-injection observation period. Saline-injected animals displayed a biphasic face-grooming response, consisting of an early, phasic phase (0-6 min) and a delayed, prolonged tonic phase (12-42 min). Memantine at doses of 2.5-10 mg/kg produced a significant dose-related inhibition of the second phase (65-93%) and a much smaller inhibition of the first phase (up to 52%). A higher dose (20 mg/kg) further inhibited both phases but also produced other motor effects (increased exploratory and decreased freezing behavior, hind-paw weakness and gait ataxia) which were not observed at the lower doses. These results suggest that the NMDA receptor antagonist Memantine can block formalin-induced tonic and, to a lesser extent, phasic pain, at doses that do not alter observed motor behaviors.

Background: Precise cannabis treatment dosing remains a major challenge, leading to physicians' reluctance to prescribe medical cannabis.Objective: To test the pharmacokinetics, analgesic effect, cognitive performance and safety effects of an innovative medical device that enables the delivery of inhaled therapeutic doses of Δ9 -Tetrahydrocannabinol (THC) in patients with chronic pain.Methods: In a randomized, three-arms, double-blinded, placebo-controlled, cross-over trial, 27 patients received a single inhalation of Δ9 -THC: 0.5mg, 1mg, or a placebo. Δ9 -THC plasma levels were measured at baseline and up to 150-min post-inhalation. Pain intensity and safety parameters were recorded on a 10-cm visual analogue scale (VAS) at pre-defined time points. The cognitive performance was evaluated using the selective sub-tests of the Cambridge Neuropsychological Test Automated Battery (CANTAB).Results: Following inhalation of 0.5 mg or 1mg, Δ9 -THC plasma Cmax  ± SD were 14.3 ± 7.7 and 33.8 ± 25.7 ng/ml. Tmax  ± SD were 3.7 ± 1.4 and 4.4 ± 2.1 min, and AUC0  → infinity ±SD were 300 ± 144 and 769 ± 331 ng*min/ml, respectively. Both doses, but not the placebo, demonstrated a significant reduction in pain intensity compared with baseline and remained stable for 150-min. The 1-mg dose showed a significant pain decrease compared to the placebo. Adverse events were mostly mild and resolved spontaneously. There was no evidence of consistent impairments in cognitive performance.Conclusion: This feasibility trial demonstrated that a metered-dose cannabis inhaler delivered precise and low THC doses, produced a dose-dependent and safe analgesic effect in patients with neuropathic pain/ complex-regional pain syndrome (CRPS). Thus, it enables individualization of medical cannabis regimens that can be evaluated pharmacokinetically and pharmacodynamically by accepted pharmaceutical models.Significance: Evidence suggests that cannabis-based medicines are an effective treatment for chronic pain in adults. The pharmacokinetics of THC varies as a function of its route of administration. Pulmonary assimilation of inhaled THC causes rapid onset of analgesia. However, currently used routes of cannabinoids delivery provide unknown doses, making it impossible to implement a pharmaceutical standard treatment plan. A novel selective-dose cannabis inhaler delivers significantly low and precise doses of THC, thus allowing the administration of inhaled cannabis-based medicines according to high pharmaceutical standards. These low doses of THC can produce safe and effective analgesia in patients with chronic pain. [ABSTRACT FROM AUTHOR]

Objective: The objectives were to evaluate the, usability, feasibility of use, satisfaction, and safety of the Syqe Inhaler Exo (Syqe Inhaler), a metered dose, Pharmacokinetics-validated, cannabis inhaler device in a cohort of hospitalized patients that were using medical cannabis under license as a part of their ongoing medical treatment.Method: Before and after inhaling from the Syqe Inhaler, participants were asked to fill a questionnaire regarding pain reduction on a visual analog scale from 0 to 10 and, if relevant, reduction in chemotherapy-induced nausea and vomiting and/or spasticity. A patient satisfaction questionnaire and a usability questionnaire were filled in following the last use. Prescribed treatment included 4 daily doses of 500 μg tetrahydrocannabinol each delivered from 16 mg cannabis flos per inhalation plus up to an additional four SOS (distress code for more doses of cannabis) doses.Result: Daily cannabis dose consumed during hospitalization with the Syqe Inhaler was 51 mg (20-96) versus 1,000 mg (660-3,300) consumed prehospitalization. Patients were easily trained and continued to use Syqe Inhaler for the duration of their hospitalization (5 [3-7] days). Pain intensity 30-60 minutes following inhalations was reported to be significantly lower than preinhalation 4 [1-5] versus 7 [2-9]). Participants ranked their satisfaction with Syqe Inhaler as 6 (5-7). Three participants reported mild cough, which resolved spontaneously.Significance Of Results: Cannabis inhalation by combustion is not feasible for hospitalized patients. The use of Syqe Inhaler during hospitalization yielded high levels of patients and staff satisfaction with no complications. [ABSTRACT FROM AUTHOR]

Background and Objective: Pain is a common symptom in patients who survive cancer and in those who live with progressive advanced disease. Evidence from meta-analyses suggests that pain remains poorly controlled for a large proportion of patients; barriers to good management include poor assessment of pain, inadequate support for patient self-management and late or inadequate access to strong opioid analgesia in those with advanced disease.Methods: The European Pain Federation (EFIC) established a Task Force in 2017 which convened a European group of experts, drawn from a diverse range of relevant clinical disciplines, to prepare a position paper on appropriate standards for the management of cancer-related pain. The expert panel reviewed the available literature and made recommendations using the GRADE system to combine quality of evidence with strength of recommendation. The panel took into account the desirable and undesirable effects of the management recommendation, including the cost and inconvenience of each when deciding the recommendation.Results and Conclusions: The 10 standards presented are aimed to improve cancer pain management and reduce variation in practice across Europe. The Task Force believes that adoption of these standards by all 37 countries will promote the quality of care of patients with cancer-related pain and reduce unnecessary suffering.Significance: Pain affects up to 40% of cancer survivors and affects at least 66% of patients with advanced progressive disease, many of whom experience poor pain control. These 10 standards are aimed to improve cancer pain management, promote the quality of care of patients and reduce variation across Europe. [ABSTRACT FROM AUTHOR]

Background: Although evidence suggests that dopaminergic systems are involved in pain processing, the effects of dopaminergic interventions on pain remains questionable. This randomized, double blinded, placebo-controlled, cross-over study was aimed at exploring the effect of the dopamine agonist apomorphine on experimental pain evoked by cold stimulation and on spontaneous pain in patients with lumbar radicular (neuropathic) pain. Methods: Data was collected from 35 patients with chronic lumbar radiculopathy (18 men, mean age 56.2±13 years). The following parameters were evaluated before (baseline) and 30, 75 and 120 minutes subsequent to a subcutaneous injection of 1.5 mg apomorphine or placebo: cold pain threshold and tolerance in the painful site (ice pack, affected leg) and in a remote non-painful site (12°C water bath, hand), and spontaneous (affected leg) pain intensity (NPS, 0–100). Results: One-hundred and twenty minutes following apomorphine (but not placebo) injection, cold pain threshold and tolerance in the hand increased significantly compared to baseline (from a median of 8.0 seconds (IQR = 5.0) to 10 seconds (IQR = 9.0), p = 0.001 and from a median of 19.5 seconds (IQR = 30.2) to 27.0 seconds (IQR = 37.5), p<0.001, respectively). In addition, apomorphine prolonged cold pain tolerance but not threshold in the painful site (from a median of 43.0 seconds (IQR = 63.0) at baseline to 51.0 seconds (IQR = 78.0) at 120 min, p = 0.02). Apomorphine demonstrated no superiority over placebo in reducing spontaneous pain intensity. Conclusion: These findings are in line with previous results in healthy subjects, showing that apomorphine increases the ability to tolerate cold pain and therefore suggesting that dopaminergic interventions can have potential clinical relevance. [ABSTRACT FROM AUTHOR]

Background: A model for measuring temporal summation (TS) by tonic noxious stimulation was recently proposed. However, methodological variations between studies make it difficult to reach a consensus regarding the way TS should be applied and calculated. The present study aimed to present a calculation method of TS magnitude produced by a tonic heat model in a large cohort of healthy subjects. Methods: Noxious heat stimulation (46.5°C/2 minutes) was applied to the forearm of 154 subjects who continuously rated pain intensity using a computerized visual analog scale. TS was calculated by "mean group" and "individual" approaches. Results: A "typical" pattern of pain response, characterized by a peak pain followed by a decrease in intensity to a nadir and subsequently a progressive increase in pain scores, was exhibited by 86.4% of the subjects. Using the "mean group" and "individual" calculation approaches, the mean ± standard deviation magnitudes of TS were 31.4±27.5 and 41.0±26.0, respectively (P,0.001). Additionally, using the individualized approach, we identified a different ("atypical") response pattern among the rest of the subjects (13.6%). Conclusion: The results support the tonic heat model of TS for future utilization. The individualized TS calculation method seems advantageous since it better reflects individual magnitudes of TS. [ABSTRACT FROM AUTHOR]

Opioid consumption by countries and health care organizations can be regarded as a marker of the quality of pain management. However, there are only limited data on opioid consumption in hospital settings. Objective and reliable data can be obtained by monitoring direct opioid consumption within a hospital, and then that data can be analyzed for identifying trends and directions to assist in guiding improved pain treatment within the hospital. This article tracks opioid consumption in a tertiary hospital over an 8-year period and by comparing the data to the consumption during the previous decade, it highlights trends and tendencies in the use of opioids as a potential indicator of pain management within this facility. [ABSTRACT FROM AUTHOR]

A discussion is presented on nurses’ knowledge and responsibilities in opioid management of pain in advanced disease patients. Documented deficiencies in some nurses’ knowledge are described. A perspective by a clinical nurse specialist also is presented. [ABSTRACT FROM AUTHOR]

The article presents the results of several studies on pain management and palliative care. One study examined the use of analgesics to treat renally impaired palliative care patients. Another study discussed the case of a young woman experiencing spinal cord injury pain and her response to pharmacotherapy, electrotherapy and kinesitherapy.

The coadministration of subantinociceptive doses of oxycodone with morphine has recently been shown to result in a synergistic antinociceptive effect in rats. The present study was aimed to investigate the possibility that coadministration of morphine and oxycodone can produce a similar synergistic effect in humans exposed to an experimental model of cold pressor test (CPT). The enriched enrolment design was used to exclude ‘stoic’ and ‘placebo responders’ in a single-blind fashion. ‘Nonstoic’, placebo ‘nonresponder’ female volunteers ( n = 30) were randomly assigned to receive 0.5 mg kg−1 oral morphine sulphate, 0.5 mg kg−1 oral oxycodone hydrochloride, and the combination of 0.25 mg kg−1 morphine sulphate with 0.25 mg kg−1 oxycodone hydrochloride, 1 week apart from each other, in a double-blind crossover design. Latency to pain onset (threshold), pain intensity (VAS), and pain tolerance (time until removal of the hand from the water) were measured six times over a 3-h period, subsequent to the administration of each medication, and were used to assess their antinociceptive effect. The combination produced a significantly higher effect on latency to pain onset than that of morphine alone [difference in mean postbaseline value 2.2; 95% confidence interval (CI) 0.48, 3.9; P = 0.01] but the effect was nonsignificantly smaller that that of oxycodone alone. Similarly, the effect of the combination on pain tolerance was significantly larger than that of morphine alone (combination difference 8.4; 95% CI 2.5, 14.3; P = 0.007), whereas oxycodone alone caused a nonsignificantly larger effect than that of the combination treatment. Comparisons of pain magnitude failed to show any significant differences between the three treatments. These results indicate that at the doses tested, morphine and oxycodone do not produce synergistic antinociceptive effects in healthy humans exposed to the CPT. [ABSTRACT FROM AUTHOR]

The World Health Organization (WHO) three-step analgesic ladder was described in 1986. It has been used and modified extensively since then. The authors ask if the second step is still needed and discuss the implications of a modified use of the ladder. [ABSTRACT FROM AUTHOR]

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed in this issue include titration of opioids for chronic nonmalignant pain, opioid tolerance versus resistance, opioids in osteoarthritis, oxycodone in visceral pain, and gender differences in pain sensitivity. [ABSTRACT FROM AUTHOR]

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. Topics addressed in this issue pertain to opioid abstinence syndrome in a complex regional pain syndrome patient whose opioid was withdrawn, and the place of perioperative pharmacotherapy in postoperative neuropathic pain. [ABSTRACT FROM AUTHOR]

The article presents a discussion of opposing the stigma around opioid analgesics, adapted from the 2007 issue of the periodical "paineurope."

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed are the characterization and management of rebound headache which was recently reclassified by the International Headache Society as medication overuse headache, the relationship between migraine headaches and risk for stroke, and opioid-induced sweating. [ABSTRACT FROM AUTHOR]

Queries from European physicians about analgesic pharmacotherapy and responses from the author are presented. The topics addressed are the safety of propoxyphene, the risk of opioid dependence in nonmalignant pain, the role of ziconotide in pain management, and titration of sustained acting opioids. [ABSTRACT FROM AUTHOR]