The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial Multicenter Study
Subcutaneous methylnaltrexone for treatment of opioid-induced constipation in patients with chronic, nonmalignant pain: a randomized controlled study.
Methylnaltrexone is effective for opioid-induced constipation (OIC) in advanced illness patients. This 4-week, double-blind, randomized, placebo-controlled study investigated the effect of subcutaneous methylnaltrexone on OIC in patients receiving opioids for chronic, nonmalignant pain. Patients (N = 460) received subcutaneous methylnaltrexone 12 mg once daily (QD) or every other day (alternating with placebo) compared with placebo. Assessments included bowel movement count, time of bowel movement, straining, sense of complete evacuation, Bristol Stool Form Scales, and quality of life. Within 4 hours of first dose, 34.2% of patients in both methylnaltrexone groups had rescue-free bowel movements (RFBMs) versus 9.9% on placebo (P < .001). The estimated number needed to treat was about 4. On average, 28.9% of methylnaltrexone QD and 30.2% of methylnaltrexone alternate-day dosing resulted in RFBMs within 4 hours versus 9.4% QD and 9.3% alternate-day placebo injections (both P < .001). Both methylnaltrexone groups had significantly shorter time to first RFBM (P < .001) and greater increase in number of weekly RFBMs (P < .05) versus placebo. Adverse events included abdominal pain, diarrhea, nausea, and hyperhidrosis. Bristol Stool Form Scale scores (P = .002) and sensation of complete evacuation (P < .04) were significantly superior with methylnaltrexone QD; both methylnaltrexone groups reported no or mild straining during RFBMs in the first 2 weeks (P < .02). At 4 weeks, a significantly greater improvement in patient-reported, constipation-specific quality of life was seen in the alternate-day dosing (P < .05) and QD (P < .001) groups. ⋯ We present data demonstrating that subcutaneous methylnaltrexone 12 mg given once daily (QD) or every other day provides significant relief of OIC and was generally well tolerated in patients with chronic, nonmalignant pain. These results expand on prior effectiveness observed for the treatment of OIC in advanced illness patients to a broader population.
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Randomized Controlled Trial
Adjusting pulse amplitude during transcutaneous electrical nerve stimulation (TENS) application produces greater hypoalgesia.
Transcutaneous electrical nerve stimulation (TENS) is a noninvasive technique used for pain modulation. During application of TENS there is a fading of current sensation. Textbooks of electrophysical agents recommend that pulse amplitude should be constantly adjusted. This seems to be accepted clinically despite the fact that there is no direct experimental evidence. The aim of the current study was to investigate the hypoalgesic effect of adjusting TENS pulse amplitude on pressure pain thresholds (PPTs) in healthy humans. Fifty-six healthy TENS naïve participants were recruited and randomly assigned to 1 of 4 groups (n = 14 per group): control, placebo TENS, fixed pulse amplitude TENS, and adjusted pulse amplitude TENS. Both active and placebo TENS were applied to the dominant forearm. PPTs were recorded from 2 points on the dominant forearm and hand before, during, and after 40 minutes of TENS. TENS increased the PPTs on the forearm (P = .003) and hand (P = .003) in the group that received the adjusted pulse amplitude when compared to all other groups. The mean final pulse amplitude for the adjusted pulse amplitude TENS group was 35.51 mA when compared to the fixed pulse amplitude TENS group, which averaged 31.37 mA (P = .0318). ⋯ These results suggest that it is important to adjust the pulse amplitude during TENS application to get the maximal analgesic effect. We propose that the fading of current sensation allows the use of higher pulse amplitudes, which would activate a greater number of and deeper tissue afferents to produce greater analgesia.
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Irritable bowel syndrome (IBS), characterized mainly by abdominal pain, is a functional bowel disorder. The present study aimed to examine changes in the excitability and the activity of the voltage-gated K(+) channel in dorsal root ganglia (DRG) neurons innervating the colon of rats subjected to neonatal maternal separation (NMS). Colonic DRG neurons from NMS rats as identified by FAST DiI™ labeling showed an increased cell size compared with those from nonhandled (NH) rats. Whole cell current-clamp recordings showed that colonic DRG neurons from NMS rats displayed: 1) depolarized resting membrane potential; 2) increased input resistance; 3) a dramatic reduction in rheobase; and 4) a significant increase in the number of action potentials evoked at twice rheobase. Whole cell voltage-clamp recordings revealed that neurons from both groups exhibited transient A-type (I(A)) and delayed rectifier (I(K)) K(+) currents. Compared with NH rat neurons, the averaged density of I(K) was significantly reduced in NMS rat neurons. Furthermore, the Kv1.2 expression was significantly decreased in NMS rat colonic DRG neurons. These results suggest that NMS increases the excitability of colonic DRG neurons mainly by suppressing the I(K) current, which is likely accounted for by the downregulation of the Kv1.2 expression and somal hypertrophy. ⋯ This study demonstrates the alteration of delayed rectifier K current and Kv1.2 expression in DRG neurons from IBS model rats, representing a molecular mechanism underlying visceral pain and sensitization in IBS, suggesting the potential of Kv1.2 as a therapeutic target for the treatment of IBS.
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The purpose of this study was to evaluate the prevalence and characteristics of pain in patients with chronic obstructive pulmonary disease (COPD) compared to a sample from the Norwegian general population. This cross-sectional study evaluated 100 COPD patients with and without pain and 333 individuals from the Norwegian population with pain. After controlling for age and sex, a significantly higher percentage of patients with COPD (45%) reported pain than the general population (34%; P = .02). No differences were found in pain intensity scores, pain interference score, or number of pain locations between COPD patients and the general population. COPD patients reported moderate-to-severe pain located primarily in the chest, shoulders, neck, and thorax. For both groups, the most common pain treatment was analgesic use. Acupuncture/transcutaneous electrical nerve stimulation was used more frequently by COPD patients (P < .001) while physiotherapy was used more frequently by the general population (P = .007) to treat their pain. Pain is a significant problem for COPD patients. Additional research is warranted to replicate these findings and to provide a more detailed characterization of how pain changes over time and influences COPD patients' ability to function and their quality of life. ⋯ Compared to the general population, pain is more common in patients with COPD and ranges from moderate to severe in its intensity.
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The aims of this study were: 1) to examine race and sex differences in primary pain appraisals and catastrophizing; 2) to test the unique ability of race, sex, primary pain appraisals, and catastrophizing to predict experimental pain outcomes; and 3) to conduct mediational analyses testing pain appraisals and catastrophizing as explanatory mechanisms for race and sex differences in pain. One hundred and fifty-five college students at The University of Alabama completed a cold pressor experimental pain task and a questionnaire battery. Statistical methods included multivariable regression models and nonparametric bootstrapping methods for tests of mediation. African-Americans reported higher catastrophizing and had lower pain tolerance than white Americans. Males demonstrated higher challenge appraisals, lower pain intensity, and longer pain tolerance. Challenge appraisals were positively related to pain tolerance, threat/harm appraisals were inversely related to pain tolerance, and pain catastrophizing was positively related to both pain intensity and pain unpleasantness. Pain catastrophizing partially mediated race differences in pain tolerance and mediated sex differences in intensity, whereas primary pain appraisals did not significantly mediate race or sex differences in pain variables. Primary appraisals and catastrophizing appear to be separable constructs related to different aspects of the pain experience. ⋯ This study found that important race and sex differences exist in relation to pain appraisals and catastrophizing, and that these cognitive variables play unique roles in different aspects of the pain experience. Cognitive-behavioral therapies for pain may be enhanced by including a focus on both pain appraisals and pain catastrophizing.