The journal of pain : official journal of the American Pain Society
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Factors associated with high-dose opioid therapy for noncancer pain are poorly understood. We documented the prevalence of high-dose opioid use as well as associated demographic, clinical, and health service utilization correlates among low back pain patients. Patients prescribed higher doses of opioids (≥100 mg/day morphine equivalent at last dispensing; n = 453) and receiving opioids for 90+ consecutive days were compared to 2 groups: lower-dose opioid group (1-99 mg/day; n = 4,815) or no-opioid group (n = 10,184). Higher-dose opioid use occurred in 2.9% of patients who received any opioids and in 8.6% of patients who received opioids long-term. The median dose in the higher-dose group was 180.0 mg/day. Compared to the no-opioid group, higher-dose users reported poorer health. Compared to either comparison group, patients in the higher-dose group had higher rates of mental health and substance use disorders, concurrent sedative-hypnotic use (60.5%; n = 274), and health service utilization. After adjusting for select covariates, male gender (odds ratio [OR] = 1.68, 95% confidence interval [CI] = 1.37-2.06), higher comorbidity, Medicare coverage (OR = 1.65, 95% CI = 1.22-2.23), any mental health or substance use diagnosis (OR = 1.58, 95% CI = 1.28-1.95), co-prescriptions of sedative-hypnotics (OR = 1.75, 95% CI = 1.42-2.16), and more emergency department and specialty pain clinic visits were associated with higher likelihood of high-dose prescriptions. ⋯ Higher-dose opioid therapy is being prescribed to 8.6% of back pain patients who receive long-term opioids. These patients had higher mental health and medical comorbidities and co-prescriptions of sedative-hypnotics, raising potential safety concerns.
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Our aim was to assess the relationship of the Val158Met polymorphism to pain, anxiety, depression, functional ability, and pressure pain sensitivity in women with fibromyalgia (FMS). One hundred (n = 100) women with FMS diagnosed according to the American College of Rheumatology criteria participated. A numerical pain rate scale (0-10) was used to assess the intensity of pain; the Hospital Anxiety and Depression Scale was calculated to determine anxiety and depression; and functional ability was determined with the Fibromyalgia Impact Questionnaire. Further, pressure pain thresholds (PPTs) were bilaterally assessed over C5-C6 zygapophyseal joints, second metacarpal, and tibialis anterior muscles. Finally, after amplifying Val158Met polymorphisms by polymerase chain reaction, catechol-O-methyltransferase (COMT) genotype was divided into Val/Val, Val/Met, or Met/Met genotypes. Women with FMS with the Met/Met genotype exhibited higher disability (F = 11.836; P < .001), anxiety (F = 13.385; P < .001), and depression (F = 6.931; P = .002) than those with Val/Val and Val/Met genotypes. No differences for the intensity of widespread pain (F = .154; P = .857) and PPT levels over C5-C6 joints (F = 1.014; P = .336), second metacarpal (F = .216; P = .806), and tibialis anterior muscle (F = 1.179; P = .311) were found. Our results suggest that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS, because women carrying the Met/Met genotype show higher disability, depression, and anxiety but similar PPTs than those with Val/Met or Val/Val genotypes. This study is important because it strives to understand potential genetic factors that predispose some women with FMS to exhibit a more severe phenotypic expression of the disease. Future studies are needed to elucidate potential relevance of the differences. ⋯ This study suggests that the Val158Met COMT polymorphism modulated some psychological variables but not pressure pain sensitivity in FMS because women with FMS carrying the Met/Met genotype exhibit higher disability, depression, and anxiety than but similar PPTs to those with Val/Met and Val/Val genotypes. This study provides further evidence of potential genetic factors that predispose women with FMS to exhibit the disease more severely.
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Sigma-1 (σ(1)) receptors play a role in different types of pain and in central sensitization mechanisms; however, it is unknown whether they are involved in chemotherapy-induced neuropathic pain. We compared the ability of paclitaxel to induce cold (acetone test) and mechanical (electronic Von Frey test) allodynia in wild-type (WT) and σ(1) receptor knockout (σ(1)-KO) mice. We also tested the effect on paclitaxel-induced painful neuropathy of BD-1063 (16-64 mg/kg, subcutaneously) and S1RA (32-128 mg/kg, subcutaneously), 2 selective σ(1) receptor antagonists that bind to the σ(1) receptor with high affinity and competitively. The responses to cold and mechanical stimuli were similar in WT and σ(1)-KO mice not treated with paclitaxel; however, treatment with paclitaxel (2 mg/kg, intraperitoneally, once per day during 5 consecutive days) produced cold and mechanical allodynia and an increase in spinal cord diphosphorylated extracellular signal-regulated kinase (pERK) in WT but not in σ(1)-KO mice. The administration of BD-1063 or S1RA 30 minutes before each paclitaxel dose prevented the development of cold and mechanical allodynia in WT mice. Moreover, the acute administration of both σ(1) receptor antagonists dose dependently reversed both types of paclitaxel-induced allodynia after they had fully developed. These results suggest that σ(1) receptors play a key role in paclitaxel-induced painful neuropathy. ⋯ Antagonists of the σ(1) receptor may have therapeutic value for the treatment and/or prevention of paclitaxel-induced neuropathic pain. This possibility is especially interesting in the context of chemotherapy-induced neuropathy, where the onset of nerve damage is predictable and preventive treatment could be administered.
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Review Meta Analysis
Conditioned pain modulation in populations with chronic pain: a systematic review and meta-analysis.
A systematic literature review and meta-analysis were undertaken to determine if conditioned pain modulation is dysfunctional in populations with chronic pain. Studies that used a standardized protocol to evaluate conditioned pain modulation in a chronic pain population and in a healthy control population were selected and reviewed. Thirty studies were included in the final review, encompassing data from 778 patients and 664 control participants. Across all studies there was a large effect size of .78, reflecting reduced conditioned pain modulation in the patient group. Analysis of moderator variables indicated a significant influence of participant gender and age on the effect size. Methodological moderator variables of type of outcome measure, type of test stimulus, type of conditioning stimulus, and the level of conditioning stimulus pain were not significant. A risk of bias assessment indicated that poor blinding of assessors and a lack of control of confounding variables were common. It is concluded that conditioned pain modulation is impaired in populations with chronic pain. Future studies should ensure adequate matching of participant age and gender between patient and control groups, blinding of the assessors obtaining the outcome measures, and more rigorous control for variables known to influence the level of modulation. ⋯ This review compared the efficacy of conditioned pain modulation between chronic pain and healthy populations. The finding of impaired modulation in the chronic pain groups highlights the dysfunction of endogenous pain modulatory mechanisms in this population.
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Spontaneous pain is often discussed in the context of both chronic inflammatory and neuropathic pain conditions, and it has been suggested that spontaneous pain, rather than stimulus-evoked pain, may be the more significant clinical problem. The following issues are discussed here. First, it is suggested that the concept of spontaneous pain makes no sense when the pain is the result of an ongoing inflammatory reaction. Evidence is reviewed that indicates that spontaneous pain is present in patients with neuropathic pain, but perhaps only in a subset of such patients. Second, it is suggested that in the presence of allodynia and hyperalgesia, stimulation from the activities of daily life occurs very many times a day and that these stimulus-evoked pains may summate to give a fluctuating level of daily pain that both patients and investigators mistake for spontaneous pain. ⋯ Which is more important-stimulus-evoked pain or spontaneous pain? This review suggests that to answer the question we will need to distinguish neuropathic spontaneous pain from inflammatory ongoing pain and to differentiate both from summated allodynic and hyperalgesic pains caused by the stimuli of daily life.