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Complex regional pain syndrome–up-to-date

imageAbstract
Complex regional pain syndrome (CRPS) was described for the first time in the 19th century by Silas Weir Mitchell. After the exclusion of other causes, CRPS is characterised by a typical clinical constellation of pain, sensory, autonomic, motor, or trophic symptoms which can no longer be explained by the initial trauma. These symptoms spread distally and are not limited to innervation territories. If CRPS is not improved in the acute phase and becomes chronic, the visible symptoms change throughout because of the changing pathophysiology; the pain, however, remains. The diagnosis is primarily clinical, although in complex cases further technical examination mainly for exclusion of alternative diagnoses is warranted. In the initial phase, the pathophysiology is dominated by a posttraumatic inflammatory reaction by the activation of the innate and adaptive immune system. In particular, without adequate treatment, central nociceptive sensitization, reorganisation, and implicit learning processes develop, whereas the inflammation moderates. The main symptoms then include movement disorders, alternating skin temperature, sensory loss, hyperalgesia, and body perception disturbances. Psychological factors such as posttraumatic stress or pain-related fear may impact the course and the treatability of CRPS. The treatment should be ideally adjusted to the pathophysiology. Pharmacological treatment maybe particularly effective in acute stages and includes steroids, bisphosphonates, and dimethylsulfoxide cream. Common anti-neuropathic pain drugs can be recommended empirically. Intravenous long-term ketamine administration has shown efficacy in randomised controlled trials, but its repeated application is demanding and has side effects. Important components of the treatment include physio- and occupational therapy including behavioural therapy (eg, graded exposure in vivo and graded motor imaging). If psychosocial comorbidities exist, patients should be appropriately treated and supported. Invasive methods should only be used in specialised centres and in carefully evaluated cases. Considering these fundamentals, CRPS often remains a chronic pain disorder but the devastating cases should become rare.

Complex regional pain syndrome–up-to-date


Orginally Published At: PAIN Reports

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Impact of patient information leaflets on pain medication intake behavior: a pilot study

imageIntroduction:
Patient information leaflets on pain medication primarily list side effects while positive effects and action mechanisms remain underrepresented. Nocebo research has shown that negative instructions can lower analgesic effects.
Objectives:
Research on information leaflets and their influence on mood, memory of side effects, and intake behavior of healthy participants is needed.
Methods:
To determine the ratio of positive to negative phrases, 18 information leaflets of common, over-the-market analgesics were examined of which 1 was selected. In a randomized, controlled study design, 18 healthy participants read this leaflet while 18 control group participants read a matched, neutral leaflet of an electrical device. Collected data concerned the recall of positive and negative contents, mood, anxiety, and the willingness to buy and take the drug.
Results:
All examined leaflets listed significantly more side effects than positive effects (t17 = 5.82, P < 0.01). After reading the analgesic leaflet, participants showed a trend towards more negative mood (F1,34 = 3.78, P = 0.06, ηp2 = 0.1), a lower intention to buy [χ2 (1, n = 36) = 12.5, P < 0.01], a higher unwillingness to take the medication [χ2 (1, n = 36) = 7.2, P < 0.01], and even a greater recall for side effects than positive effects (t17 = 7.47, P < 0.01).
Conclusion:
Reading the patient information leaflets can increase fear and lower the intention to buy and the willingness to take a pain medication.

Impact of patient information leaflets on pain medication intake behavior: a pilot study


Orginally Published At: PAIN Reports

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Pharmacoeconomics of genotyping-based treatment decisions in patients with chronic pain

imageAbstractIntroduction:Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain.Objectives:To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting.Methods:A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results.Results:Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to $24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to $18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain.Conclusion:Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials.
Introduction:
Genotyping-based treatment decisions may optimize treatment response and minimize adverse drug events (ADEs) in patients with chronic pain.
Objectives:
To estimate the financial impact of genotyping-based treatment decisions in patients with moderate to severe chronic pain in a managed care setting.
Methods:
A budget impact model was built with a 1-year time horizon to estimate costs of genotyping-based treatment decisions in a 1000-patient cohort. The model includes drug costs, type and cost of ADEs, distribution of treatments used, and genotyping costs. Event rates and health care costs were derived from primary literature. Three patient cohorts were assessed with and without genotyping-based treatment decisions: no genetic testing; 50% genetic testing; and 100% genetic testing. Sensitivity analysis was performed varying costs, adherence, and the percentage of patients treated according to genotyping results.
Results:
Medical and ADE costs varied by patient severity and genotyping rates. Without genotyping, drug and ADE costs ranged from $1,544,377 to $24,313,844. With genotyping-based treatment, total costs ranged from $1,780,922 to $18,868,032. Sensitivity analysis, varying costs, adherence, and genotyping rates suggested genotyping improves outcomes and is cost saving in patients with chronic pain.
Conclusion:
Genotyping-based treatment costs are offset by reduced medication utilization and adverse event costs. Genotyping should be considered for patients with chronic pain in clinical practice and within clinical trials.

Pharmacoeconomics of genotyping-based treatment decisions in patients with chronic pain


Orginally Published At: PAIN Reports

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Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States

imageAbstractIntroduction:Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP.Objectives:We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data.Methods:A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP.Results:Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year.Conclusion:Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.
Introduction:
Low back pain (LBP) is among the leading indications for the prescription of opioid analgesics in clinical practice. There is increasing evidence suggesting that these agents may have diminished efficacy in the treatment of LBP.
Objectives:
We evaluated the relationship between depression, the probability of receiving an opioid prescription, and the amount of morphine equivalent amounts prescribed per year among patients with LBP using nationwide data.
Methods:
A cross-sectional analysis was performed on existing data from the Medical Expenditure Panel Survey data set from the period 2004 to 2009. Demographic, medical condition, Patient Health Questionnaire-2 responses, and prescription drug information were obtained on 56,811,864 weighted person-years of data from individuals aged 18 to 65 with an ICD-9 code specific to LBP.
Results:
Increases in PHQ-2 score, as well a positive screen for depression, were associated with an increased probability of being prescribed opioid therapy and more morphine equivalents per year.
Conclusion:
Analysis of a nationwide sample of patients with LBP shows an association between depression and higher rates of opioid prescribing after controlling for several known cofounders. Clinicians prescribing opioids in LBP populations that rely on clinical trial results that exclude depressed patients may misjudge the risks and benefits of this class of therapy.

Differences in opioid prescribing in low back pain patients with and without depression: a cross-sectional study of a national sample from the United States


Orginally Published At: PAIN Reports

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Women report higher pain intensity at a lower level of inflammation after knee surgery compared with men

imageIntroduction and Objectives:
We previously found that women report more pain after knee arthroscopic procedures than men. It remains unclear whether this is due to different biochemical responses or nociceptive mechanisms.
Methods:
We analyzed acute pain-related inflammatory markers in a clinical model of patient self-reported pain immediately after knee surgery. To simultaneously measure 92 inflammatory biomarkers, we used the proximity extension assay with the Proseek Multiplex Inflammation I panel (Olink Bioscience, Uppsala, Sweden). Knee surgery was performed under general anesthesia with propofol and remifentanil. Analgesic drugs were only administered on patient request.
Results:
Women were 4.9 times more likely to report moderate or severe pain than men (95% confidence interval, 1.2–19.6, P = 0.024). Patient age, preoperative pain, and surgery duration were not significant factors. We analyzed synovial fluids from 44 patients (23 women, 21 men). After false discovery rate correction, MMP-10 was the only biomarker that was higher among men (P = 0.01). Linear discriminant analysis showed that 3 proteins (IL-8, CCL-4, and MCP-2) were expressed at higher levels in men, with differences of >1 normalized protein expression. No proteins were overexpressed by >1 normalized protein expression in women.
Conclusion:
Acute pain after knee arthroscopy was more intense in women, but pro-inflammatory biomarkers and MMP-10 were higher in men. Further knowledge of cytokine function is required before concluding that the disparities in biomarker expression are clinically unimportant. The similar biochemical signaling between sexes suggests that central mechanisms are of greater importance in sex-specific joint pain perception.

Women report higher pain intensity at a lower level of inflammation after knee surgery compared with men


Orginally Published At: PAIN Reports

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Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy

imageIntroduction:
Alleviation of pain, by either medical or surgical therapy, is accompanied by transition from less efficient, or pro-nociceptive, to efficient conditioned pain modulation (CPM). Spontaneous decrease or resolution of pain with disease progression is reported for some patients with painful diabetic neuropathy (PDN).
Objectives:
To explore whether CPM changes similarly in parallel to spontaneous resolution of pain in PDN patients.
Methods:
In this cross-sectional study, thirty-three patients with PDN underwent psychophysical assessment of pain modulation on the forearm, remote from the clinical pain.
Results:
Pain duration was not correlated with neuropathic pain intensity, yet, it correlated with CPM efficiency; patients with longer pain duration had same pain level, but more efficient CPM than those with short-pain duration (ρ = −0.417; P = 0.025, Spearman correlation). Patients with pain more than 2 years (median split) expressed efficient CPM that was not different from that of healthy controls. These patients also had lower temporal summation of pain than the short-pain duration patients group (P < 0.05). The 2 patient groups did not differ in clinical pain characteristics or use of analgesics.
Conclusion:
Pro-nociception, expressed by less efficient CPM and high temporal summation that usually accompanies clinical painful conditions, seems to “normalize” with chronicity of the pain syndrome. This is despite continuing pain, suggesting that pro-nociceptivity in pain syndromes is multifactorial. Because the pain modulation profile affects success of therapy, this suggests that different drugs might express different efficacy pending on duration of the pain in patients with PDN.

Efficient conditioned pain modulation despite pain persistence in painful diabetic neuropathy


Orginally Published At: PAIN Reports

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The dark side of opioids in pain management: basic science explains clinical observation

imageIntroduction:
In the past 2 decades, opioids have been used increasingly for the treatment of persistent pain, and doses have tended to creep up. As basic science elucidates mechanisms of pain and analgesia, the cross talk between central pain and opioid actions becomes clearer.
Objectives:
We aimed to examine the published literature on basic science explaining pronociceptive opioid actions, and apply this knowledge to clinical observation.
Methods:
We reviewed the existing literature on the pronociceptive actions of opioids, both preclinical and clinical studies.
Results:
Basic science provides a rationale for the clinical observation that opioids sometimes increase rather than decrease pain. Central sensitization (hyperalgesia) underlies pain chronification, but can also be produced by high dose and high potency opioids. Many of the same mechanisms account for both central pain and opioid hyperalgesia.
Conclusion:
Newly revealed basic mechanisms suggest possible avenues for drug development and new drug therapies that could alter pain sensitization through endogenous and exogenous opioid mechanisms. Recent changes in practice such as the introduction of titration-to-effect for opioids have resulted in higher doses used in the clinic setting than ever seen previously. New basic science knowledge hints that these newer dosing practices may need to be reexamined. When pain worsens in a patient taking opioids, can we be assured that this is not because of the opioids, and can we alter this negative effect of opioids through different dosing strategies or new drug intervention?

The dark side of opioids in pain management: basic science explains clinical observation


Orginally Published At: PAIN Reports