The journal of pain : official journal of the American Pain Society
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Familial amyloid polyneuropathy (FAP) caused by transthyretin (TTR) mutation is a small-fiber predominant polyneuropathy, exposing patients with TTR-FAP to development of neuropathic pain. However, the painful nature of TTR-FAP has never been specifically addressed. In this study, we compared 2 groups of 16 patients with either painless or painful TTR-FAP with regard to various clinical and neurophysiologic variables, including laser evoked potential (LEP) recording and quantitative sensory testing. The 2 groups of patients did not differ on any clinical or neurophysiologic variable. Patients with painful TTR-FAP complained of ongoing burning pain sensations, pain aggravation at rest, paroxysmal pain (electric shock and stabbing sensations), or provoked pain (mostly dynamic mechanical allodynia). However, the symptomatic presentation of painful TTR-FAP evolved with the course of the disease. The duration of the disease and the severity of small-fiber lesions (increase in thermal thresholds and reduction in LEP amplitude) correlated negatively with the intensity of ongoing burning sensations and positively with the intensity of paroxysmal pain. In addition, small-fiber preservation correlated positively with cold allodynia and pain aggravation at rest and negatively with dynamic mechanical allodynia. Peripheral sensitization of small-diameter nociceptive axons might occur in early TTR-FAP and be responsible for the burning sensation and cold allodynia. As polyneuropathy and small-fiber loss progress, paroxysmal pain and dynamic mechanical allodynia may develop as a result of central sensitization generated by abnormal activities affecting relatively spared large-diameter sensory fibers. ⋯ Pain in TTR-FAP includes several mechanisms varying with the course of the disease and the involvement of the different types of nerve fibers.
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The present study examined whether pain catastrophizing and pain-related fear predict the experience of pain in body regions that are not targeted by an experimental muscle injury protocol. A delayed-onset muscle soreness (DOMS) protocol was used to induce pain unilaterally in the pectoralis, serratus, trapezius, latissimus dorsi, and deltoid muscles. The day after the DOMS protocol, participants were asked to rate their pain as they lifted weighted canisters with their targeted (ie, injured) arm and their nontargeted arm. The lifting task is a nonnoxious stimulus unless participants are already experiencing musculoskeletal pain. Therefore, reports of pain on the nontargeted arm were operationalized as pain in response to a nonnoxious stimulus. Eighty-two healthy university students (54 men, 28 women) completed questionnaires on pain catastrophizing and fear of pain and went through the DOMS protocol. The analyses revealed that catastrophizing and pain-related fear prospectively predicted pain experience in response to a nonnoxious stimulus. The possible mechanisms underlying this effect and clinical implications are discussed. ⋯ Pain catastrophizing and fear of pain prospectively predict the pain experience in response to a nonnoxious stimulus. The pattern of findings is consistent with the predictions of current models of generalization of pain-related fear.
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Randomized Controlled Trial Comparative Study
Manual Physical Therapy versus Surgery for Carpal Tunnel Syndrome: a Randomized Parallel-Group Trial.
This randomized clinical trial investigated the effectiveness of surgery compared with physical therapy consisting of manual therapies including desensitization maneuvers in carpal tunnel syndrome (CTS). The setting was a public hospital and 2 physical therapy practices in Madrid, Spain. One hundred twenty women with CTS were enrolled between February 2013 and January 2014, with 1-year follow-up completed in January 2015. Interventions consisted of 3 sessions of manual therapies including desensitization maneuvers of the central nervous system (physical therapy group, n = 60) or decompression/release of the carpal tunnel (surgical group, n = 60). The primary outcome was pain intensity (mean pain and the worst pain), and secondary outcomes included functional status and symptoms severity subscales of the Boston Carpal Tunnel Questionnaire and the self-perceived improvement. They were assessed at baseline and 1, 3, 6, and 12 months by a blinded assessor. Analysis was by intention to treat. At 12 months, 111 (92%) women completed the follow-up (55/60 physical therapy, 56/60 surgery). Adjusted analyses showed an advantage (all, P < .01) for physical therapy at 1 and 3 months in mean pain (Δ -2.0 [95% confidence interval (CI) -2.8 to -1.2]/-1.3 [95% CI -2.1 to -.6]), the worst pain (Δ -2.9 [-4.0 to -2.0]/-2.0 [-3.0 to -.9]), and function (Δ -.8 [-1.0 to -.6]/-.3 [-.5 to -.1]), respectively. Changes in pain and function were similar between the groups at 6 and 12 months. The 2 groups had similar improvements in the symptoms severity subscale of the Boston Carpal Tunnel Questionnaire at all follow-ups. In women with CTS, physical therapy may result in similar outcomes on pain and function to surgery.
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Sickle cell disease (SCD) is a hemoglobinopathy that affects more than 100,000 individuals in the United States. The disease is characterized by the presence of sickle hemoglobin and recurrent episodes of pain. Some individuals with SCD experience frequent hospitalizations and a high burden of pain. The role of central mechanisms in SCD pain has not been explored. Twenty-five adolescents and young adults with SCD underwent functional magnetic resonance imaging. Participants were stratified into groups with high pain or low pain based on the number of hospitalizations for pain in the preceding 12 months. Resting state functional connectivity was analyzed using seed-based and dual regression independent component analysis. Intrinsic brain connectivity was compared between the high pain and low pain groups, and association with fetal hemoglobin, a known modifier of SCD, was explored. Patients in the high pain group displayed an excess of pronociceptive connectivity such as between anterior cingulate and default mode network structures, such as the precuneus, whereas patients in the low pain group showed more connectivity to antinociceptive structures such as the perigenual and subgenual cingulate. Although a similar proportion of patients in both groups reported that they were on hydroxyurea, the fetal hemoglobin levels were significantly higher in the low pain group and were associated with greater connectivity to antinociceptive structures. These findings support the role of central mechanisms in SCD pain. Intrinsic brain connectivity should be explored as a complementary and objective outcome measure in SCD pain research. ⋯ Altered connectivity patterns associated with high pain experience in patients with sickle cell disease suggest a possible role of central mechanisms in sickle cell pain. Resting state brain connectivity studies should be explored as an effective methodology to investigate pain in SCD.
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Randomized Controlled Trial
Effect of Milnacipran Treatment on Ventricular Lactate in Fibromyalgia : A Randomized, Double-blind, Placebo-controlled Trial.
Milnacipran, a serotonin/norepinephrine reuptake inhibitor, has been approved by the US Food and Drug Administration for the treatment of fibromyalgia (FM). This report presents the results of a randomized, double-blind, placebo-controlled trial of milnacipran conducted to test the hypotheses that a) similar to patients with chronic fatigue syndrome, patients with FM have increased ventricular lactate levels at baseline; b) 8 weeks of treatment with milnacipran will lower ventricular lactate levels compared with baseline levels and with ventricular lactate levels after placebo; and c) treatment with milnacipran will improve attention and executive function in the Attention Network Test compared with placebo. In addition, we examined the results for potential associations between ventricular lactate and pain. Baseline ventricular lactate measured by proton magnetic resonance spectroscopic imaging was found to be higher in patients with FM than in healthy controls (F1,37 = 22.11, P < .0001, partial η(2) = .37). Milnacipran reduced pain in patients with FM relative to placebo but had no effect on cognitive processing. At the end of the study, ventricular lactate levels in the milnacipran-treated group had decreased significantly compared with baseline and after placebo (F1,18 = 8.18, P = .01, partial η(2) = .31). A significantly larger proportion of patients treated with milnacipran showed decreases in both ventricular lactate and pain than those treated with placebo (P = .03). These results suggest that proton magnetic resonance spectroscopic imaging measurements of lactate may serve as a potential biomarker for a therapeutic response in FM and that milnacipran may act, at least in part, by targeting the brain response to glial activation and neuroinflammation. ⋯ Patients treated with milnacipran showed decreases in both pain and ventricular lactate levels compared with those treated with placebo, but, even after treatment, levels of ventricular lactate remained higher than in controls. The hypothesized mechanism for these decreases is via drug-induced reductions of a central inflammatory state.