The journal of pain : official journal of the American Pain Society
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Randomized Controlled Trial
Antagonistic effects of ondansetron and tramadol? A randomized placebo and active drug controlled study.
Opposing effects of ondansetron and tramadol on the serotonin pathway have been suggested which possibly increase tramadol consumption and emesis when co-administered. In a randomized, double-blinded study, 179 patients received intravenous ondansetron, metoclopramide, or placebo for emesis prophylaxis. Analgesic regimen consisted of tramadol intraoperative loading and subsequent patient-controlled analgesia. Tramadol consumption and response to antiemetic treatment were compared. Additionally, plasma concentrations of ondansetron and (+)O-demethyltramadol and CYP2D6 genetic variants were analyzed as possible confounders influencing analgesic and antiemetic efficacy. Tramadol consumption did not differ between the groups. Response rate to antiemetic prophylaxis was superior in patients receiving ondansetron (85.0%) compared with placebo (66.7%, P = .046), with no difference to metoclopramide (69.5%). Less vomiting was reported in the immediate postoperative hours in the verum groups (ondansetron 5.0%, metoclopramide 5.1%) compared with placebo (18.6%; P = .01). Whereas plasma concentrations of (+)O-demethyltramadol were significantly correlated to CYP2D6 genotype, no influence was detected for ondansetron. Co-administration of ondansetron neither increased tramadol consumption nor frequency of PONV in this postoperative setting. ⋯ Controversial findings were reported for efficacy of tramadol and ondansetron when co-administered due to their opposing serotonergic effects. Co-medication of these drugs neither increased postoperative analgesic consumption nor frequency of emesis in this study enrolling patients recovering from major surgery.
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Central sensitization is one form of long-term plasticity in the central nervous system. Sustained activation of primary sensory fibers supplying dorsal horn can induce long-lasting increases in the discharge amplitude of primary afferent synapses. This is similar to the long-term potentiation that occurs in many other CNS regions. Drugs that limit the short-duration wind-up component of central sensitization include sodium channel blockers, NMDA antagonists, fast-acting opioids and the calcium-channel ligands gabapentin and pregabalin (S-3-(aminomethyl)-5-methylhexanoic acid). Pregabalin, like gabapentin, binds selectively to the Ca(V)α₂δ auxiliary subunit of presynaptic voltage-gated calcium channels. The conformational changes induced by this binding inhibit abnormally intense neuronal activity by reducing the synaptic release of glutamate and other neurotransmitters. Recent identification in animal models of increased Ca(V)α₂δ protein expression in chronic pain, allodynia, and hyperalgesia have drawn additional interest to drugs that bind the Ca(V)α₂δ site. Experimental studies with animal models and healthy human volunteers have shown that pregabalin reduces nociceptive responses, particularly in conditions involving central sensitization. Since these actions occur with relatively modest effects on physiological and cognitive functions, pregabalin may be an important consideration in the pharmacotherapy of otherwise difficult-to-treat pain syndromes. ⋯ This focus article discusses how the central nervous system plasticity phenomenon, central sensitization, is established in the induction and maintenance of chronic pain, allodynia, and hyperalgesia. In addition, it explores the neurophysiologic actions of the calcium-channel ligands gabapentin and pregabalin in limiting pathological manifestations of central sensitization.
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This study examined the assessment of pain intensity and pain distress with the Numerical Rating Scale (NRS) in elderly patients (age > 60 years) with persistent pain. A consecutive sample of 800 elderly patients were categorized by age into 3 groups: 61 to 70 years (n = 366), 71 to 80 years (n = 308), and 81 years and over (n = 126). Participants completed 3 Numerical Rating Scales assessing current pain intensity, and both the usual level of pain and average pain distress in the preceding week. The failure rate for scale completion was low for all scales for all age groups, but was significantly higher in the oldest group compared to the youngest group for the scales assessing current pain intensity and average pain distress in the preceding week. The NRS was shown to be a reliable and valid measure of pain intensity and pain distress in all these age groups. Distress related to pain appeared to be specific to the pain experience and was only weakly related to more generalized affective distress. These findings confirm that measures of pain intensity and pain distress, like the NRS, capture only part of the pain experience in older patients and should be supplemented by other measures in the assessment process. ⋯ This article confirms the utility of the Numerical Rating Scale (NRS) as a measure of pain intensity and pain distress in elderly patients with persistent pain. The use of a large sample increases confidence in the psychometric soundness of the NRS with this population.
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Emerging evidence suggests that some individuals with regional pain disorders go on to develop chronic widespread pain (CWP). However, the mechanism behind this transition and the nature of risk factors that predispose a person to develop CWP remain to be elucidated. The purpose of this study was to describe the frequency with which participants with chronic back or neck pain develop CWP and to determine the risk factors associated with this development. In a sample of 512 individuals, we found that nearly a quarter (22.6%) of subjects who presented with regional back or neck pain in 2001/2002 had developed CWP by 2007. Logistic regression indicated that 7 factors were associated with the transition to CWP: moderate or severe pain intensity, female gender, history of abuse, family history of CWP, severe interference with general activity, having 1 or more central sensitivity syndromes, and using more pain management strategies. History of abuse was not significant in multivariate analysis. Notably, number of depressive symptoms endorsed, pain duration, age, body mass index, number of medication classes used, and receipt of disability benefits were not significantly associated with this transition. ⋯ This study offers insight into risk factors associated with the development of CWP. This information not only offers clues as to the mechanism behind the expansion of pain sensitivity from a regional pain locus to a widespread pain disorder but also provides insight as to how clinicians might mitigate this transition.
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Evaluating pain in verbal children in the hospital setting is done primarily through serial assessments of pain intensity using single-item measures. However, little remains known about intensity scales' relative responsiveness and uniqueness from negative affect in this clinical setting. In the present study, a total of 411 assessments using 3 common pediatric pain intensity measures (the Faces Pain Scale-Revised, a verbally presented numeric rating scale, and a visual analog scale) were obtained over a period of 3 days from 29 children ages 9 to 18 years following a relatively standardized surgical procedure. Hierarchical linear models were used to compare the 3 scales on responsiveness over postoperative recovery time, invariance across baseline variables (age, sex, and baseline mood), and distinctiveness from changes in negative affect. Results showed that all 3 pain-intensity measures were highly interrelated, varied similarly with age and baseline state anxiety, and were comparably related to contemporaneous changes in affect. However, patients tended to rate pain intensity higher on the Numerical Rating Scale, and only this scale failed to reflect a decreasing trend in pain scores with elapsed surgical recovery time. Potential implications for clinical practice are discussed. ⋯ This article presents data comparing the responsiveness over time and association with negative affect of 3 single-item pediatric pain-intensity scales commonly used in hospital settings. The results can help inform the selection of self-report measures when serially evaluating pain and treatment response in hospitalized children.