Pain
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Randomized Controlled Trial
Morphine, nortriptyline and their combination vs. placebo in patients with chronic lumbar root pain.
Although lumbar radicular pain is the most common chronic neuropathic pain syndrome, there have been few randomized studies of drug treatments. We compared the efficacy of morphine (15-90 mg), nortriptyline (25-100 mg), their combination, and a benztropine "active placebo" (0.25-1 mg) in patients with chronic sciatica. Each period consisted of 5 weeks of dose escalation, 2 weeks of maintenance at the highest tolerated doses, and 2 weeks of dose tapering. ⋯ Mean doses were: nortriptyline alone, 84+/-24.44 (SD) mg/day; morphine alone, 62+/-29 mg/day; and combination, morphine, 49+/-27 mg/day plus nortriptyline, 55 mg+/-33.18 mg/day. Over half of the study completers reported some adverse effect with morphine, nortriptyline or their combination. Within the limitations of the modest sample size and high dropout rate, these results suggest that nortriptyline, morphine and their combination may have limited effectiveness in the treatment of chronic sciatica.
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Prior studies evaluating predictors of pain-related outcomes following treatment for sciatica have been limited by methodological problems, including retrospective study design, use of unvalidated outcome measures, and short-term follow-up periods. Despite these limitations, some reports have suggested that symptoms of psychological distress may predict individual differences in pain treatment-related outcomes (e.g., higher levels of depressive and anxious symptomatology are associated with greater pain and disability after treatment). In this study, we sought to determine whether acute symptoms of depression and anxiety were prospectively associated with treatment outcomes over a 3-year follow-up period in surgically treated and non-surgically treated patients with sciatica. ⋯ In most analyses, symptoms of depression and anxiety, both at baseline and at the preceding time point, were significant independent predictors of worse pain and function after controlling for relevant covariates. Collectively, elevated distress appears to be a significant risk factor for reduced treatment benefit (i.e., less improvement in pain and disability) over short and medium-term follow-up periods in patients with sciatica. Future research should determine whether the prospective identification and treatment of patients with high levels of distress (a "yellow flag") is associated with improved treatment outcomes.
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Pain is a complex human trait. It is likely that the interaction of multiple genes, each with a small individual effect, along with the effect of environmental factors, influences the clinical efficacy of opioids rather than a single gene alone. Polymorphisms in genes coding for the mu-opioid receptor (A118G) and catechol-O-methyl transferase (Val158Met) may be important modulators of opioid efficacy. ⋯ When we explored for joint effects, we found that carriers of the OPRM1 AA and COMT Met/Met genotype required the lowest morphine dose to achieve pain relief (87 mg/24 h; 95%CI=57,116) and those with neither Met/Met nor AA genotype needed the highest morphine dose (147 mg/24 h; 95%CI=100,180). The significant joint effects for the Met/Met and AA genotypes (p<0.012) persisted, even after controlling for demographic and clinical variables in the multivariable analyses. Future studies are needed to further characterize the joint effects of multiple genes, along with demographic and clinical variables, in predicting opioid dose.
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Provoked vestibulodynia is a common cause of superficial dyspareunia in young women. Recent evidence has pointed out the importance of studying endogenous pain modulation in these women. An impairment of diffuse noxious inhibitory controls (DNIC) has been suggested in chronic pain conditions with a female predominance such as fibromyalgia and temporomandibular disorder. ⋯ No differences related to the intake of COC were observed between the healthy women. In conclusion, women with provoked vestibulodynia as well as healthy women irrespective of COC status display a DNIC response indicating an endogenous pain inhibition. However, the results imply a systemic hypersensitivity in women with vestibulodynia with low general pain thresholds as compared to healthy women.
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The level and pattern of daily activities performed by persons with chronic pain are regarded as central determinants of their overall physical, social and emotional functioning. Within the chronic pain literature, various approaches to activity are typically considered, including activity avoidance, "pacing", and particular patterns of high rate activity, sometimes referred to as "overuse" or "activity cycling". Of these, activity avoidance has been most studied, while the others remain poorly understood. ⋯ Groups with the most avoidance and disability reported the lowest levels of acceptance of pain. These data suggest that activity patterns are complex and multidimensional, and that avoidance appears to be the overriding process with regard to daily functioning. Moreover, avoidance patterns may be subtle, sometimes resembling healthy coping, and sometimes presenting along side patterns of high activity.