Pain
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Randomized Controlled Trial Multicenter Study
Sensory profiles of patients with neuropathic pain based on the neuropathic pain symptoms and signs.
This manuscript aimed to characterize the clinical profile of various neuropathic pain (NeP) disorders and to identify whether patterns of sensory symptoms/signs exist, based on baseline responses on the Neuropathic Pain Symptom Inventory (NPSI) questionnaire and the quantitative sensory testing (QST). These post hoc analyses were based on data from 4 randomized, double-blind, placebo-controlled clinical studies of pregabalin (150-600mg/day) in patients with NeP syndromes: central poststroke pain, posttraumatic peripheral pain, painful HIV neuropathy, and painful diabetic peripheral neuropathy. The NPSI questionnaire includes 10 different pain symptom descriptors. ⋯ Based on QST signs, PCA identified 2 pain dimensions: evoked by cold and evoked by touch. A hierarchical cluster analysis identified 4 clusters with distinct pain characteristics profiles. These "trans-etiological" profiles may reflect distinct pathophysiological mechanisms and therefore, potential differential responses to treatment.
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The gate theory of pain, published by Ronald Melzack and Patrick Wall in Science in 1965, was formulated to provide a mechanism for coding the nociceptive component of cutaneous sensory input. The theory dealt explicitly with the apparent conflict in the 1960s between the paucity of sensory neurons that responded selectively to intense stimuli and the well-established finding that stimulation of the small fibers in peripheral nerves is required for the stimulus to be described as painful. ⋯ The clarity of the model and its description gave this article immediate visibility, with numerous attempts made to test its various predictions. Although subsequent experiments and clinical findings have made clear that the model is not correct in detail, the general ideas put forth in the article and the experiments they prompted in both animals and patients have transformed our understanding of pain mechanisms.
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Glial cells are being increasingly implicated in mechanisms underlying pathological pain, and recent studies suggest glial gap junctions involving astrocytes may contribute. The aim of this study was to examine the effect of a gap junction blocker, carbenoxolone (CBX), on medullary dorsal horn (MDH) nociceptive neuronal properties and facial mechanical nociceptive behavior in a rat trigeminal neuropathic pain model involving partial transection of the infraorbital nerve (p-IONX). p-IONX produced facial mechanical hypersensitivity reflected in significantly reduced head withdrawal thresholds that lasted for more than 3weeks. p-IONX also produced central sensitization in MDH nociceptive neurons that was reflected in significantly increased receptive field size, reduction of mechanical activation threshold, and increases in noxious stimulation-evoked responses. Intrathecal CBX treatment significantly attenuated the p-IONX-induced mechanical hypersensitivity and the MDH central sensitization parameters, compared to intrathecal vehicle treatment. These results provide the first documentation that gap junctions may be critically involved in orofacial neuropathic pain mechanisms.
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Injection of hypertonic saline into deep tissues of the back (subcutis, muscle, or the surrounding fascia) can induce acute low back pain (LBP). So far, no study has analyzed differences in temporal, qualitative, and spatial pain characteristics originating from these tissues. The current study aimed to investigate the role of the thoracolumbar fascia as a potential source of LBP. ⋯ Pain radiation and pain affect evoked by fascia injection exceeded those of the muscle (P<0.01) and the subcutis significantly (P<0.05). Pain descriptors after fascia injection (burning, throbbing, and stinging) suggested innervation by both A- and C-fiber nociceptors. These findings show that the thoracolumbar fascia is the deep tissue of the back that is most sensitive to chemical stimulation, making it a prime candidate to contribute to nonspecific LBP but not to localized pressure hyperalgesia.
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In experimental and clinical pain studies, the sex of subjects was rarely taken into account, even if nociceptive inputs appear to be processed and modulated by partially distinct neural mechanisms in each sex. In this study we analysed, in male and female mice, behavioural and neuronal responses in developing, maintaining, and recovering from neuropathic pain. Experiments were carried out in adult CD1 mice by using Chronic Constriction Injury (CCI) as neuropathic pain model. ⋯ Proteomic analysis confirmed sex-related differences of proteins associated with nerve regenerative processes. In addition, the reactive gliosis induced by CCI at day 7, as revealed by colocalization of glial fibrillary acidic protein (astrocytes) and CD11b (microglia) with phosphorylated p38, disappeared 121 days after CCI in male but not in female mice. These results may have important therapeutic implications for the treatment of neuropathic pain.