Summary
The aim of the present study was to investigate the effects of nabilone on capsaicin‐induced pain and hyperalgesia, as well as on biomarkers of cannabinoid central nervous system (CNS) ...effects.
A randomized, double‐blind, placebo‐controlled, crossover study was conducted in 30 healthy male volunteers receiving single doses of nabilone (1, 2 or 3 mg). Pain intensity after intradermal capsaicin injections in the forearm was assessed by continuous visual analogue scale (0–100 mm). Capsaicin cream was applied to the calf to induce hyperalgesia. Primary hyperalgesia was assessed by measuring heat pain thresholds, whereas secondary hyperalgesia was assessed by measuring the area where light tactile stimulation was felt to be painful. Pain and hyperalgesia were measured at baseline and 2–3.5 h after dosing. The CNS effects were assessed at baseline and up to 24 h after dosing using visual analogue mood scales for feeling ‘stimulated’, ‘anxious’, ‘sedated’ and ‘down’. Plasma samples for pharmacokinetic analysis were obtained up to 24 h after drug administration.
Nabilone did not significantly attenuate either ongoing pain or primary or secondary hyperalgesia, whereas dose‐dependent CNS effects were observed from 1.5 to 6 h after dosing, being maximal at 4–6 h. Plasma concentrations of nabilone and its metabolite carbinol were maximal 1–2 h after dosing. Adverse events (AE) were common on nabilone treatment. Four subjects withdrew due to pronounced CNS AE (anxiety, agitation, altered perception, impaired consciousness).
Although nabilone had marked CNS effects, no analgesic or antihyperalgesic effects were observed.
AZD1386 was well tolerated, with rapid but short-lasting analgesia despite sustained plasma concentration.
The effects of a TRPV1 antagonist (AZD1386) were investigated in patients with acute pain. ...After removal of a mandibular third molar and at request of analgesia 103 patients randomly received 95mg AZD1386 (n=40), placebo (n=40) or 500mg naproxen (n=23) in a double-blind manner. Plasma samples were drawn, and pain intensity and body temperature were measured during 8h after drug administration. The pain intensity difference from drug intake was calculated as a percentage (PID%) and as a weighted sum over the 8h (SPID%0–8h). The time to first perceptible and first meaningful pain relief was recorded. SPID%0–8h showed no significant difference between AZD1386 and placebo (P=.132) but between naproxen and placebo (P=.038). AZD1386 had a rapid short-lasting analgesia and compared to placebo, PID% was significantly higher (P⩽.026) at 0.25, 0.50, 0.75 and 1.00h after drug administration. Correspondingly, for naproxen significantly higher PID% (P⩽.021) was seen at 2.5, 3, 4, 5, 6, 7 and 8h. The frequency of patients obtaining perceptible and meaningful pain relief was about 85% and 48% after AZD1386 and about 53% and 25% after placebo. The occurrence of perceptible and meaningful pain relief was significantly faster (P=.002 and P=.031) for AZD1386 compared to placebo. Adverse events were similar to placebo with the exception of 2 patients reporting chills. The highest individual body temperature after AZD1386 was 38.1°C, recorded in 2 patients. In summary, AZD1386 was well tolerated with a rapid analgesia that was short lasting despite sustained plasma concentration.
Background and Aims
Healthy women have generally been found to have increased experimental pain perception and chronic pain has a higher prevalence in female as compared to male patients. However, no ...study has investigated whether pain intensity and pain perception thresholds are distinct or similar between sexes within various chronic pain entities. We investigated whether average pain intensities and pain thresholds assessed using quantitative sensory testing (QST) differed between women and men suffering from three distinct chronic pain conditions: Complex Regional Pain Syndrome (CRPS type I), peripheral nerve injury (PNI) or polyneuropathy (PNP), as compared to paired healthy volunteers.
Methods
QST data of 1,252 patients (669 female, 583 male) with PNI (n = 342), PNP (n = 571) or CRPS (n = 339), and average pain intensity reports from previously published studies were included. Absolute and z‐values (adjusted for age and body region) of cold, heat, pressure (PPT) and pinprick pain thresholds were compared in generalized linear models with aetiology, duration of underlying pain disease and average pain intensity as fixed effects.
Results
Average pain intensity during the past four weeks did not differ between women and men, in both mean and range. In women absolute pain thresholds for cold, heat and pinprick were lower than in males across all diagnoses (p < .05). However, after z‐transformation these differences disappeared except for PPT in CRPS (p = .001).
Discussion
Pain thresholds in patients show only minor sex differences. However, these differences mimic those observed in healthy subjects and do not seem to be linked to specific pathophysiological processes.
Significance
Female healthy participants and female patients with neuropathic pain conditions or CRPS I report lower pain thresholds compared to males, but pain intensity is similar and there is no sex difference in the extent to which the thresholds are altered in neuropathic pain or CRPS. Thus, the sex differences observed in various chronic pain conditions mimic those obtained in healthy participants, indicating that these differences are not linked to specific pathophysiological processes and are of minor clinical relevance.
The pathophysiology of pain in neuropathy is complex and may be linked to sensory phenotypes. Quantitative sensory testing, a standardized method to evaluate sensory profiles in response to defined ...stimuli, assesses functional integrity of small and large nerve fiber afferents and central somatosensory pathways. It has revealed detailed insights into mechanisms of neuropathy, yet it remains unclear if pain directly affects sensory profiles. The main objective of this study was to investigate sensory profiles in patients with various neuropathic conditions, including polyneuropathy, mononeuropathy, and lesions to the central nervous system, in relation to self-reported presence or absence of pain and pain sensitivity using the Pain Sensitivity Questionnaire. A total of 443 patients (332 painful and 111 painless) and 112 healthy participants were investigated. Overall, loss of sensation was equally prevalent in patients with and without spontaneous pain. Pain thresholds were equally lowered in both patient groups, demonstrating that hyperalgesia and allodynia are just as present in patients not reporting any pain. Remarkably, this was similar for dynamic mechanical allodynia. Hypoalgesia was more pronounced in painful polyneuropathy, whereas hyperalgesia was more frequent in painful mononeuropathy (compared with painless conditions). Self-reported pain sensitivity was significantly higher in painful than in painless neuropathic conditions. Our results reveal the presence of hyperalgesia and allodynia in patients with central and peripheral lesions of the somatosensory system not reporting spontaneous pain. This shows that symptoms and signs of hypersensitivity may not necessarily coincide and that painful and painless neuropathic conditions may mechanistically blend into one another.
This article summarizes the results of a meeting convened by the Initiative on Methods, Measurement, and Pain Assessment in Clinical Trials (IMMPACT) on key considerations and best practices ...governing the design of acute pain clinical trials. We discuss the role of early phase clinical trials, including pharmacokinetic-pharmacodynamic (PK-PD) trials, and the value of including both placebo and active standards of comparison in acute pain trials. This article focuses on single-dose and short-duration trials with emphasis on the perioperative and study design factors that influence assay sensitivity. Recommendations are presented on assessment measures, study designs, and operational factors. Although most of the methodological advances have come from studies of postoperative pain after dental impaction, bunionectomy, and other surgeries, the design considerations discussed are applicable to many other acute pain studies conducted in different settings.
Objective. The purpose of this study was to investigate whether a single injection of bupivacaine with adrenaline close to the fascia could decrease opiate consumption and pain in patients undergoing ...cesarean section in spinal anesthesia. Design. Randomized double‐blind controlled study. Settings. Karolinska University Hospital, Huddinge, Sweden. Population. 260 women scheduled for elective cesarean section were enrolled in the study. Methods. The treatment group (n= 130) received 40 mL bupivacaine (2.5 mg/mL) with adrenaline (5 μg/mL) (Marcain® adrenalin) and the control group (n= 130) received 40 mL saline solution (0.9%), which was, in both groups, injected close to the fascia before closure of the wound. Main outcome measures. Morphine consumption and mean resting pain intensity numerical rating scale at 12 and 24 hours were the primary outcome variables. Other assessments for pain as well as mobilization parameters were considered secondary. Results. Morphine requirements were significantly less in the bupivacaine group, 19.0 mg/woman, compared with 24.0 mg/woman in the placebo group, during the first 12 postoperative hours. During this time period there was also a trend towards a difference between groups in mean pain intensity, but significant only during the first six hours. Over the whole first postoperative 24 hours, there were no differences in either morphine requirement or pain intensity between groups. Conclusions. A single injection of bupivacaine with adrenaline in the surgical wound decreases the need for morphine requirements for the first 12 postoperative hours and contributes to safe and effective pain management in women undergoing cesarean section.
Highlights • Oral OXY – better post-caesarean section pain control vs. nurse-administered i.v. morphine/oral codeine. • Oral OXY – less opioid consumption with oxycodone vs. i.v. morphine/oral ...codeine. • Oral OXY – less time consuming than giving i.v. morphine during the first 24 h. • Both treatment protocols are safe for both the mother and the newborn.
Neuropathic pain highly affects quality of life, well-being, and function. It has recently been shown based on cluster analysis studies that most patients with neuropathic pain may be categorized ...into 1 of 3 sensory phenotypes: sensory loss, mechanical hyperalgesia, and thermal hyperalgesia. If these phenotypes reflect underlying pathophysiological mechanisms, they may be more relevant for patient management than underlying neurological diagnosis or pain intensity. The aim of this study was thus to examine the impact of these sensory phenotypes on mental health, functionality, and quality of life. Data of 433 patients from the IMI/EuroPain network database were analyzed, and results of HADS-D/A, Pain Catastrophizing Scale, Euro Quality of Life 5D/-VAS, Brief Pain Inventory, and Graded Chronic Pain Scale between the sensory phenotypes were compared using multiple regression analysis. There was no difference in chronic pain grade, pain intensity, depression, or anxiety scores between phenotypes. Pain interference (Brief Pain Inventory) was higher (P = 0.002); self-reported health state lower (Euro Quality of Life 5D VAS, P = 0.02); and problems regarding mobility (P = 0.008), usual activities (P = 0.004), and self-care (P = 0.039) more prominent (EQ5-D) in the sensory loss compared with the thermal hyperalgesia phenotype. Patients with sensory loss also showed higher pain catastrophizing scores (P = 0.006 and 0.022, respectively) compared with the 2 other groups. Sensory phenotype is associated with the impact of neuropathic pain conditions on well-being, daily functionality, and quality of life but is less associated with pain intensity. These results suggest that the somatosensory phenotype should be considered for personalized pain management.
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