The journal of pain : official journal of the American Pain Society
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Aconitine and its structurally-related diterpenoid alkaloids have been shown to interact differentially with neuronal voltage-dependent sodium channels, which was suggested to be responsible for their analgesia and toxicity. Bulleyaconitine A (BAA) is an aconitine analogue and has been prescribed for the management of pain. The present study aimed to evaluate the inhibitory effects of BAA on pain hypersensitivity and morphine antinociceptive tolerance, and explore whether the expression of dynorphin A in spinal microglia was responsible for its actions. Single intrathecal or subcutaneous (but not intraventricular or local) injection of BAA blocked spinal nerve ligation-induced painful neuropathy, bone cancer-induced pain, and formalin-induced tonic pain by 60 to 100% with the median effective dose values of 94 to 126 ng per rat (intrathecal) and 42 to 59 μg/kg (subcutaneous), respectively. After chronic treatment, BAA did not induce either self-tolerance to antinociception or cross-tolerance to morphine antinociception, and completely inhibited morphine tolerance. The microglial inhibitor minocycline entirely blocked spinal BAA (but not exogenous dynorphin A) antinociception, but failed to attenuate spinal BAA neurotoxicity. In a minocycline-sensitive and lidocaine- or ropivacaine-insensitive manner, BAA stimulated the expression of dynorphin A in the spinal cord, and primary cultures of microglia but not of neurons or astrocytes. The blockade effects of BAA on nociception and morphine tolerance were totally eliminated by the specific dynorphin A antiserum and/or κ-opioid receptor antagonist. Our results suggest that BAA eliminates pain hypersensitivity and morphine tolerance through directly stimulating dynorphin A expression in spinal microglia, which is not dependent on the interactions with sodium channels. ⋯ The newly illustrated mechanisms underlying BAA antinociception help us to better understand and develop novel dynorphin A expression-based painkillers to treat chronic pain.
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Evidence from a number of sources supports the existence of two relatively independent neurophysiological systems that underlie avoidance- and approach-related emotions, cognitions, and behavior. There is considerable overlap between 1) the emotions, cognitions, and behaviors controlled by these two systems, and 2) the known effects of chronic pain. Here we propose a 2-factor model of chronic pain on the basis of these well established 2-factor models, and discuss the implications of the model for understanding the effects of pain and mechanisms of psychological pain treatments. The model makes specific hypotheses, which are unique to the proposed model, regarding the mechanisms underlying pain's negative influence and the benefits of psychological pain treatments. The model also provides an overarching framework that could enhance outcomes by 1) broadening the assessment of factors that may be influencing pain and its effect on individual patients, and 2) suggesting that specific techniques from different treatments may be combined to better target these factors. ⋯ The 2-factor model presented in this report provides a framework for understanding the effects of psychological pain treatments, and makes specific a priori hypotheses regarding the specific mechanisms of those treatments. Clinical applications of the model have the potential for enhancing treatment outcomes.
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Review
The Pain Experience of Hispanic Americans: A Critical Literature Review and Conceptual Model.
Although the Hispanic population is a burgeoning ethnic group in the United States, little is known about their pain-related experience. To address this gap, we critically reviewed the existing literature on pain experience and management among Hispanic Americans (HAs). We focused our review on the literature on nonmalignant pain, pain behaviors, and pain treatment seeking among HAs. Pain management experiences were examined from HA patients' and health care providers' perspectives. Our literature search included variations of the term "Hispanic" with "AND pain" in PubMed, Embase, Web of Science, ScienceDirect, and PsycINFO databases. A total of 117 studies met our inclusion criteria. We organized the results into a conceptual model with separate categories for biological and/or psychological and sociocultural and/or systems-level influences on HAs' pain experience, response to pain, and seeking and receiving pain care. We also included information on health care providers' experience of treating HA patients with pain. For each category, we identified future areas of research. We conclude with a discussion of limitations and clinical implications. ⋯ In this critical review of the literature we examined the pain and management experiences of the HA population. We propose a conceptual model, which highlights findings from the existing literature and future areas of research.
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By 2007, opioid-related mortality in Washington state (WA) was 50% higher than the national average, with Medicaid patients showing nearly 6 times the mortality of commercially-insured patients. In 2007, the WA Interagency Guideline on Opioid Dosing for Chronic Non-cancer Pain was released, which recommended caution in prescribing >120 mg morphine-equivalent dose per day for patients not showing clinically meaningful improvement in pain and function. We report on opioid dosing in the WA Medicaid fee-for-service population for 273,200 adults with a paid claim for an opioid prescription between April 1, 2006 and December 31, 2010. Linear regression was used to test for trends in dosing over that time period, with quarter-year as the independent variable and median daily dose as the dependent variable. Prescription opioid use among WA Medicaid adults peaked in 2009, as evidenced by the unique number of opioid users (105,232), the total number of prescriptions (556,712), and the total person-years of prescription opioid use (29,442). Median opioid dose was unchanged from 2006 to 2010 at 37.5 mg morphine-equivalent dose, but doses at the 75th, 90th, 95th, and 99th percentiles declined significantly (P < .001). These results suggest that opioid treatment guidelines with dosing guidance may be able to reduce high-dose opioid use without affecting the median dose used. ⋯ Some fear that opioid dosing guidelines might restrict access to opioid therapy for patients who could benefit. However, there is evidence that high-dose opioid therapy entails significant risks without demonstrated benefit. These findings indicate that high-dose opioid therapy can be reduced without altering median opioid dose in a Medicaid population.
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In this large, sham-controlled, randomized trial, we examined the efficacy of the combination of standard treatment and paraspinous lidocaine injection compared with standard therapy alone in subjects with chronic low back pain. There is little research-based evidence for the routine clinical use of paraspinous lidocaine injection for low back pain. A total of 378 subjects with nonspecific chronic low back pain were randomized to 3 groups: paraspinous lidocaine injection, analgesics, and exercises (group 1, LID-INJ); sham paraspinous lidocaine injection, analgesics, and exercises (group 2, SH-INJ); and analgesics and exercises (group 3, STD-TTR). A blinded rater assessed the study outcomes at 3 time points: baseline, after treatment, and after 3 months of follow-up. There were increased frequency of pain responses and better low back functional scores in the LID-INJ group compared with the SH-INJ and STD-TTR groups. These effects remained at the 3-month follow-up but differed between all 3 groups. There were significant changes in pain threshold immediately after treatment, supporting the effects of this intervention in reducing central sensitization. Paraspinous lidocaine injection therapy is not associated with a higher risk of adverse effects compared with conventional treatment and sham injection. Its effects on hyperalgesia might correlate with changes in central sensitization. ⋯ There are few data to support paraspinous lidocaine injection use in patients with nonspecific chronic low back pain. Our results show that this therapy when combined with standard therapy significantly increases the number of responders versus standard treatment alone. Its effects on hyperalgesia might correlate with a change in central sensitization.