The journal of pain : official journal of the American Pain Society
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Clinical research often relies on retrospective recall of symptom levels, but the information contained in these ratings is not well understood. The "peak-and-end rule" suggests that the most intense (peak) and final (end) moments of an experience disproportionately influence retrospective judgments, which may bias self-reports of somatic symptoms. This study examined the extent to which peak and end symptom levels systematically affect patients' day-to-day recall of pain and fatigue. Rheumatology patients (N = 97) completed 5 to 6 momentary ratings of pain and fatigue per day as well as a daily recall rating of these symptoms for 28 consecutive days. For pain, peak and end momentary ratings predicted daily recall of average pain beyond the actual average of momentary ratings. This effect was small, yet was confirmed in both between-person and within-person (repeated measures) analyses. For fatigue, neither peak nor end momentary symptoms significantly contributed to daily recall. Of note, the evidence for peak- and end-effects in recall of pain and fatigue varied significantly between individual patients. These findings suggest that peak- and end-effects create a small bias in recall reports of pain, but not fatigue. However, there are considerable individual differences in susceptibility to peak and end heuristics. ⋯ The peak-end cognitive heuristic could bias end-of-day recall of pain and fatigue. An effect was shown for pain, but not for fatigue. The effects were small and were unlikely to substantially bias end-of-day assessments. Individuals were shown to differ in the degree that the heuristic was associated with recall.
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Randomized Controlled Trial Multicenter Study
A randomized, placebo-controlled phase 3 trial (Study SB-767905/013) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.
The balance between the pain relief provided by opioid analgesics and the side effects caused by such agents is of particular significance to patients who take opioids for the long-term relief of non-cancer pain. The spectrum of signs and symptoms affecting the gastrointestinal (GI) tract associated with opioid use is known as opioid-induced bowel dysfunction. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist, approved in the US for the management of postoperative ileus in patients undergoing bowel resection (short-term, in-hospital use only). Alvimopan was under clinical development for long-term treatment of opioid-induced constipation (OIC) but this program has been discontinued. This double-blind, placebo-controlled trial, part of the former OIC development program, enrolled patients (N = 485) receiving opioids for non-cancer pain. Patients were randomized to receive alvimopan .5 mg once daily, alvimopan .5 mg twice daily, or placebo, for 12 weeks. The primary efficacy endpoint was the proportion of patients who experienced ≥ 3 spontaneous bowel movements (SBMs; bowel movements with no laxative use in the previous 24 hours) per week over the treatment period, and an average increase from baseline of ≥ 1 SBM per week. There were greater proportions of SBM responders in both alvimopan treatment groups (63% in both groups) compared with placebo (56%), although these differences were not statistically significant. Secondary efficacy analyses indicated that alvimopan was numerically superior to placebo in improving opioid-induced bowel dysfunction symptoms and patients' global assessment of opioid-induced bowel dysfunction, and reduced the requirement for rescue laxatives. Active treatment was well tolerated and alvimopan did not antagonize opioid analgesia. ⋯ Although the primary endpoint was not met in this study, the magnitude of alvimopan-induced improvements versus baseline, together with previous study results, suggest that a PAM-OR antagonist has the potential to improve OIC.
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We explored the contribution of median nerve small (Aδ, C)-and large (Aβ)-fiber damage to the severity and topographic distribution of sensory symptoms in carpal tunnel syndrome (CTS) and the timing of fiber damage across CTS stages. We recruited 106 CTS patients. After selection, 49 patients were included. They underwent electrodiagnostic and quantitative sensory testing (QST) study and were asked on the severity of Boston Carpal Tunnel Questionnaire (BCTQ) Symptoms Severity Scale, daytime pain (DP), night pain and paresthesia, on the distribution of hand symptoms, and the presence of proximal symptoms. BCTQ Symptoms Severity Scale and DP severity was significantly correlated with Aδ-fiber damage. Small-fiber QST measures were impaired in electrodiagnostic-negative CTS patients and did not change across CTS neurographic stages. QST findings were not correlated to the topographical distribution of symptoms. Aδ-fiber damage contributes to CTS symptoms and in particular to DP. Night pain and paresthesia might be ascribed to ectopic fiber discharges secondary to median nerve enhanced mechanosensitivity. Small-fiber damage takes place earlier than large fiber. Median nerve fiber involvement does not directly contribute to extraterritorial symptoms spread. Our data may help understanding CTS pathophysiology and explain the well-known discrepancy between CTS symptoms and electrodiagnostic findings. ⋯ We explored the involvement of median nerve small and large fibers in carpal tunnel syndrome (CTS). We found a significant correlation between Aδ-fiber function and CTS symptoms. Small-fiber involvement took place in milder disease stages. These findings could help reconcile the discrepancy between CTS symptoms and electrodiagnostic data.
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The purpose of this study was to demonstrate a method for increasing the precision and information yield of postoperative pain assessment. We recorded pain intensity ratings over 6 days after surgery in 502 elective surgery patients and examined individual pain trajectories. A linear fit of an individual patient's scores defines a trajectory with two features: (1) the intercept or initial pain intensity; and (2) the slope, or rate of pain resolution. Three pain trajectory patterns emerged from examination of the pain trajectory slopes. Most patients (63% of the sample) demonstrated a negative slope trajectory characterized by a decline in pain intensity over days after surgery. Other patients (25% of the sample) demonstrated a flat trajectory with no meaningful change over 6 days from pain they reported initially. A third patient group (12% of the sample) had a positive slope trajectory in which pain scores increased over 6 days after surgery. Measures derived from individual pain trajectories yielded much lower standard errors of measurement and therefore had better measurement precision than did conventional pain assessment methods. Pain trajectory measures proved sufficiently precise to characterize pain patterns reliably in individual patients. ⋯ Progress in acute pain management requires effective pain assessment. The acute pain trajectory quantifies rate of pain resolution as well as pain intensity. It affords more precise measurement than conventional pain assessment and can identify abnormal postoperative pain resolution.
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Randomized Controlled Trial
Effects of the N-methyl-D-aspartate receptor on temporal summation of second pain (wind-up) in irritable bowel syndrome.
Irritable bowel syndrome (IBS) is a common gastrointestinal disorder in which the pathophysiological mechanisms of the pain and hypersensitivity are not well understood. IBS patients frequently complain of pain in body regions somatotopically distinct from the gut, suggesting that central hyperalgesic mechanisms may be involved. In the current study, during the wind-up testing session, a series of 6 heat pulses were presented with an interstimulus interval (ISI) of 3 seconds. Following the 1st, 3rd, and 6th thermal stimuli, subjects were asked to rate the late thermal sensation or second pain. IBS patients who demonstrated temporal summation of pain (TSSP) then received dextromethorphan and placebo in a randomized, double-blind, fashion to block wind-up. The results showed: 1) a subset of IBS patients, but not controls, showed TSSP in response to a series of noxious heat pulses; and 2) TSSP was blocked by administration of dextromethorphan, an NMDA receptor antagonist. In summary, these findings further elucidate mechanisms of somatic hypersensitivity in a subset of IBS patients. Our results also support an etiologic basis for abnormal NMDA receptor mechanisms in some IBS patients. Future studies are needed to determine if NMDA receptor antagonists may be used to treat IBS patients. ⋯ This study evaluates temporal summation of second pain in a subset of IBS patients that is blocked by Dextromethorphan, an NMDA receptor antagonist. Theses results could lead to the use of an NMDA receptor antagonist in the treatment of pain in a subset of IBS patients.