The journal of pain : official journal of the American Pain Society
-
Randomized Controlled Trial Multicenter Study
A randomized, placebo-controlled phase 3 trial (Study SB-767905/012) of alvimopan for opioid-induced bowel dysfunction in patients with non-cancer pain.
Gastrointestinal (GI) side effects are common with opioid medication, and constipation affects ∼40% of patients. Such symptoms considerably impair patients' quality of life. Alvimopan is an orally administered, systemically available, peripherally acting mu-opioid receptor (PAM-OR) antagonist approved in the US for short-term, in-hospital management of postoperative ileus in patients undergoing bowel resection. This double-blind, placebo-controlled trial was conducted as part of a recently discontinued clinical program, in which alvimopan was being developed for opioid-induced constipation (OIC). Patients (N = 518) receiving opioids for non-cancer pain 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 experiencing ≥ 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. A significantly greater proportion of patients in the alvimopan .5 mg twice-daily group met the primary endpoint compared with placebo (72% versus 48%, P < .001). Treatment with alvimopan twice daily improved a number of other symptoms compared with placebo and reduced the requirement for rescue laxative use. The opioid-induced bowel dysfunction Symptoms Improvement Scale (SIS) responder rate was 40.4% in the alvimopan .5 mg twice daily group, versus 18.6% with placebo (P < .001). In general, alvimopan .5 mg once daily produced qualitatively similar but numerically smaller responses than twice-daily treatment. Active treatment did not increase the requirement for opioid medication or increase average pain intensity scores. Over the 12-week treatment period, alvimopan appeared to be well tolerated. ⋯ These results demonstrate the potential for a PAM-OR antagonist to improve the symptoms of OIC without antagonizing opioid analgesia.
-
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.
-
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.
-
Randomized Controlled Trial Comparative Study
Reduced analgesic effect of acupuncture-like TENS but not conventional TENS in opioid-treated patients.
Evidence from recent animal studies indicates that the analgesic effect of low-frequency transcutaneous electrical nerve stimulation (TENS) is reduced in opioid-tolerant animals. The aim of the present study was to compare the analgesic effect of conventional (high frequency) and acupuncture-like (low frequency) TENS between a group of opioid-treated patients and a group of opioid-naive patients in order to determine if this cross-tolerance effect is also present in humans. Twenty-three chronic pain patients (11 who took opioids and 12 who did not) participated in the study. Participants were assigned in a randomized crossover design to receive alternately conventional and acupuncture-like TENS. There was a significant reduction in pain during and after conventional TENS when compared to baseline for both the opioid and nonopioid group (P < .01). For acupuncture-like TENS however, the analgesic effect of TENS was only observed in the nonopioid group (P < .01), with opioid-treated patients showing no change in pain scores during and after TENS when compared to baseline (P > .09). The reduced analgesic effect of acupuncture-like TENS in opioid-treated patients is coherent with previous animal studies and suggests that conventional TENS should be preferred in patients taking opioids on a regular basis. ⋯ This study shows that patients taking opioids on a regular basis are less susceptible to benefit from acupuncture-like TENS. This phenomenon is probably attributable to the fact that the analgesia induced by acupuncture-like TENS and opioids are mediated by the same receptors (ie, μ opioid receptors).
-
Western studies document the prevalence of chronic pain in the general adult population to be between 2 and 55%. Knowing the prevalence of chronic pain among Chinese populations provides important comparative perspective: To determine the prevalence of chronic pain in the general population of Hong Kong; evaluate the relationship of chronic pain with sociodemographic and lifestyle factors; and describe the pain characteristics among chronic pain sufferers. A total of 5,001 adults aged ≥ 18 years (response rate 58%) drawn from the general population of Hong Kong completed the Chronic Pain Grade (CPG) questionnaire, providing information on chronic pain and sociodemographic status using telephone interviews. Overall 34.9% reported pain lasting more than 3 months (chronic pain), having an average of 1.5 pain sites; 35.2% experienced multiple pain sites, most commonly of the legs, back, and head with leg and back being rated as the most significant pain areas among those with multiple pain problems. The CPG criteria classified 21.5% of those with chronic pain symptoms as Grade III or above. Fully adjusted stepwise regression analyses identified being female, older age, divorced/separated, having part-time employment, existing long-term health problems, higher HADS Anxiety scores, poor QoL (mental health component), and low self-perceived health to be significantly associated with chronic pain. ⋯ Our data evidenced that chronic pain is common in the general population of Hong Kong, and the prevalence is highest among women and middle-aged adults.