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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Ischemic myalgia is a unique type of muscle pain in the patient population. The role that discrete muscle afferent subpopulations play in the generation of pain during ischemic events, however, has yet to be determined. Using 2 brachial artery occlusion models to compare prolonged ischemia or transient ischemia with reperfusion of the muscles, we found that both injuries caused behavioral decrements in grip strength, as well as increased spontaneous pain behaviors. Using our ex vivo forepaw muscles, median and ulnar nerves, dorsal root ganglion, and spinal cord recording preparation, we found after both prolonged and transient ischemia that there was a significant increase in the number of afferents that responded to both noxious and non-noxious chemical (lactate, adenosine triphosphate, varying pH) stimulation of the muscles compared to uninjured controls. However, we found an increase in firing to heat stimuli specifically in muscle afferents during prolonged ischemia, but a distinct increase in afferent firing to non-noxious chemicals and decreased mechanical thresholds after transient ischemia. The unique changes in afferent function observed also corresponded with distinct patterns of gene expression in the dorsal root ganglia. Thus, the development of ischemic myalgia may be generated by unique afferent-based mechanisms during prolonged and transient ischemia. ⋯ This study analyzed the response properties of thinly myelinated group III and unmyelinated group IV muscle afferents during prolonged and transient ischemia in addition to pain behaviors and alterations in DRG gene expression in the mouse. Results suggest that mechanisms of pain generation during prolonged ischemia may be different from ischemia/reperfusion.
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Fentanyl, introduced more than 50 years ago, has become the most often used opioid for intraoperative analgesia. Since the early 1990s the fentanyl patch has been available for management of chronic pain of all forms of cancer as well as the persistent, intense pain from many noncancerous maladies. ⋯ The purpose of this article is to describe why this opioid has become so important in the treatment of pain in modern clinical practice. The data indicate that fentanyl's popularity has occurred because it has minimal cardiovascular effects, does not result in increases in plasma histamine, is relatively short in onset of action and duration of effect, is easy and inexpensive to synthesize and prepare for the marketplace, and is now familiar to clinicians working in pain and perioperative medicine throughout the world.
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Disorders of pain neural systems are frequently chronic and, when recalcitrant to treatment, can severely degrade the quality of life. The pain pathway begins with sensory neurons in dorsal root or trigeminal ganglia, and the neuronal subpopulations that express the transient receptor potential cation channel, subfamily V, member 1 (TRPV1) ion channel transduce sensations of painful heat and inflammation and play a fundamental role in clinical pain arising from cancer and arthritis. In the present study, we elucidate the complete transcriptomes of neurons from the TRPV1 lineage and a non-TRPV1 neuroglial population in sensory ganglia through the combined application of next-gen deep RNA-Seq, genetic neuronal labeling with fluorescence-activated cell sorting, or neuron-selective chemoablation. RNA-Seq accurately quantitates gene expression, a difficult parameter to determine with most other methods, especially for very low and very high expressed genes. Differentially expressed genes are present at every level of cellular function from the nucleus to the plasma membrane. We identified many ligand receptor pairs in the TRPV1 population, suggesting that autonomous presynaptic regulation may be a major regulatory mechanism in nociceptive neurons. The data define, in a quantitative, cell population-specific fashion, the molecular signature of a distinct and clinically important group of pain-sensing neurons and provide an overall framework for understanding the transcriptome of TRPV1 nociceptive neurons. ⋯ Next-gen RNA-Seq, combined with molecular genetics, provides a comprehensive and quantitative measurement of transcripts in TRPV1 lineage neurons and a contrasting transcriptome from non-TRPV1 neurons and cells. The transcriptome highlights previously unrecognized protein families, identifies multiple molecular circuits for excitatory or inhibitory autocrine and paracrine signaling, and suggests new combinatorial approaches to pain control.