The journal of pain : official journal of the American Pain Society
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The amygdala contributes to the generation of pain affect, and the amygdaloid central nucleus (CeA) receives nociceptive input that is mediated by glutamatergic neurotransmission. The present study compared the contribution of N-methyl-d-aspartate (NMDA) receptor agonism and antagonism in the CeA to generation of the affective response of rats to an acute noxious stimulus. Vocalizations that occur following a brief tail shock (vocalization afterdischarges) are a validated rodent model of pain affect and were preferentially suppressed, in a dose-dependent manner, by bilateral injection into the CeA of NMDA (.1, .25, .5, or 1 μg/side) or the NMDA receptor antagonist d-(-)-2-amino-5-phosphopentanoic acid (AP5; 1, 2, or 4 μg/side). Vocalizations that occur during tail shock were suppressed to a lesser degree, whereas spinal motor reflexes (tail flick and hind limb movements) were unaffected by injection of NMDA or AP5 into the CeA. Injection of NMDA, but not AP5, into the CeA increased c-Fos immunoreactivity in the ventrolateral periaqueductal gray, and unilateral injection of the μ-opiate receptor antagonist H-d-Phe-Cys-Tyr-d-Trp-Arg-Thr-Pen-Thr-NH2 (CTAP; .25 μg) into ventrolateral periaqueductal gray prevented the antinociception generated by injection of NMDA into the CeA. These findings demonstrate that although NMDA receptor agonism and antagonism in the CeA produce similar suppression of pain behaviors, they do so via different neurobiologic mechanisms. ⋯ The amygdala contributes to production of the emotional dimension of pain. NMDA receptor agonism and antagonism within the CeA suppressed rats' emotional response to acute painful stimulation. Understanding the neurobiology underlying emotional responses to pain will provide insights into new treatments for pain and its associated affective disorders.
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Interindividual variability exists in persistent breast pain following breast cancer surgery. Recently, we used growth mixture modeling to identify 3 subgroups of women (N = 398) with distinct persistent breast pain trajectories (ie, mild, moderate, severe) over 6 months following surgery. The purposes of this study were to identify demographic and clinical characteristics that differed among the breast pain classes and, using linear mixed effects modeling, to examine how changes over time and in sensitivity in the breast scar area, pain qualities, pain interference, and hand and arm function differed among these classes. Several demographic and clinical characteristics differentiated the breast pain classes. Of note, 60 to 80% of breast scar sites tested were much less sensitive than the unaffected breast. Significant group effects were observed for pain qualities and interference scores, such that, on average, women in the severe pain class reported higher scores than women in the moderate pain class. In addition, women in the moderate pain class reported higher scores than women in the mild pain class. Compared to women in the mild pain class, women in the severe pain class had significantly impaired grip strength, and women in the moderate and severe pain classes had impaired flexion and abduction. ⋯ Subgroups of women with persistent postsurgical breast pain differed primarily with respect to the severity rather than the nature or underlying mechanisms of breast pain. Pervasive sensory loss and the association between persistent breast pain and sustained interference with function suggest the need for long-term clinical follow-up.
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Persistent pain following breast cancer surgery is well documented. However, it is not well characterized in terms of the anatomic site affected (ie, breast, arm). In 2 separate growth mixture modeling analyses, we identified subgroups of women (N = 398) with distinct breast pain and arm pain trajectories. The fact that these latent classes differed by anatomic site, types of tissue affected, and neural innervation patterns suggests the need for separate evaluations of these distinct persistent pain conditions. The purposes of this companion study were to identify demographic and clinical characteristics that differed between the 2 arm pain classes and determine if differences existed over time in sensitivity in the upper inner arm and axillary lymph node dissection sites, pain qualities, pain interference, and hand and arm function, as well as to compare findings with persistent breast pain. Higher occurrence rates for depression and lymphedema were found in the moderate arm pain class. Regardless of pain group membership, sensory loss was observed in the upper inner arm and axillary lymph node dissection site. Arm pain was described similarly to neuropathic pain and interfered with daily functioning. Persistent arm pain was associated with sustained impairments in shoulder mobility. ⋯ For persistent breast and arm pain, changes in sensation following breast cancer surgery were notable. Persistent arm pain was associated with sustained interference with daily functioning and upper body mobility impairments. Long-term management of persistent pain following breast cancer surgery is warranted to improve the quality of survivorship for these women.
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Chronic pain represents an immense clinical problem. With tens of millions of people in the United States alone suffering from the burden of debilitating chronic pain, there is a moral obligation to reduce this burden by improving the understanding of pain and treatment mechanisms, developing new therapies, optimizing and testing existing therapies, and improving access to evidence-based pain care. Here, we present a goal-oriented research agenda describing the American Pain Society's vision for pain research aimed at tackling the most pressing issues in the field. ⋯ This article presents the American Pain Society's view of some of the most important research questions that need to be addressed to advance pain science and to improve care of patients with chronic pain.
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Randomized Controlled Trial Multicenter Study
Lenalidomide for complex regional pain syndrome type 1: lack of efficacy in a phase II randomized study.
Complex regional pain syndrome (CRPS) is a potentially debilitating chronic pain syndrome with a poorly understood but likely neuroimmune/multifactorial pathophysiology associated with axonal injury. Based on the potential contribution of proinflammatory cytokines to CRPS pathogenesis and prior research with thalidomide, we investigated lenalidomide, a thalidomide derivative, for CRPS treatment. We conducted a phase II, randomized, double-blind, placebo-controlled study to evaluate the efficacy of oral lenalidomide 10 mg once daily in consenting patients with unilateral or bilateral CRPS type 1. The study comprised 12 weeks of treatment followed by a long-term extension. The primary efficacy outcome was reduced pain in the index limb, defined as ≥30% improvement from baseline using an 11-point numeric rating scale. One hundred eighty-four subjects enrolled. The primary endpoint was not met because equal proportions of treated (16.1%) and control (16.1%) subjects achieved the outcome; however, lenalidomide was well tolerated, with no evidence of neuropathy or major adverse effects. This study is the largest controlled, blinded clinical trial in subjects with chronic CRPS using the Budapest research criteria. It demonstrates the feasibility of conducting high-quality clinical trials in CRPS type 1 and provides considerations for designing future trials. ⋯ This article reports an adequately powered, controlled clinical trial in subjects with CRPS. Treatment and placebo were equally effective, but the study demonstrated that lenalidomide treatment is feasible in this population. The study provides examples to consider in designing future CRPS trials.