Pain
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Prior research supports the validity and short-term test-retest stability of 4 commonly used scales for assessing pain intensity (Visual Analogue Scale [VAS], 6-point Verbal Rating Scale [VRS-6], Numerical Rating Scale [NRS-11], and Face Pain Scale-Revised [FPS-R]). However, the relative stability and ability of these measures to detect changes in pain intensity over longer time periods have not yet been examined, although knowledge regarding these psychometric issues is important for selecting from among these measures. To address this knowledge gap, we administered these scales assessing worst and average pain intensity to 250 chronic pain outpatients on 2 occasions, a little over 6 weeks apart on average. ⋯ However, the psychometric properties of the scales were not influenced by education level. Overall, the NRS-11 emerged as showing the most sensitivity and stability. The FPS-R seems to be a good second choice to consider for samples of individuals who might have difficulty understanding or using the NRS-11.
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Trigeminal neuralgia (TN) is a rare but debilitating disorder characterized by excruciating facial pain, with a higher incidence in women. Recent studies demonstrated that TN patients present mutations in the gene encoding the Ca V 3.2 T-type calcium channel, an important player in peripheral pain pathways. We characterize the role of Ca V 3.2 channels in TN at 2 levels. ⋯ The effect of Z944 was absent in Ca V 3.2 -/- mice, indicating that Ca V 3.2 is the molecular target of the antihyperalgesic Z944 effect. Finally, enzyme-linked immunosorbent assay analysis revealed increased Ca V 3.2 channel expression in the spinal trigeminal subnucleus caudalis. Altogether, the present study demonstrates an important role of Ca V 3.2 channels in trigeminal pain.
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Ample data support a prominent role of peripheral T-type calcium channels 3.2 (Ca V 3.2) in generating pain states. Development of primary sensory neuron-specific inhibitors of Ca V 3.2 channels is an opportunity for achieving effective analgesic therapeutics, but success has been elusive. Small peptides, especially those derived from natural proteins as inhibitory peptide aptamers (iPAs), can produce highly effective and selective blockade of specific nociceptive molecular pathways to reduce pain with minimal off-target effects. ⋯ Two prototype Ca V 3.2iPAs (iPA1 and iPA2) derived from the IDRs of Ca V 3.2 intracellular loops 2 and 3, respectively, were expressed selectively in the primary sensory neurons of dorsal root ganglia in vivo using recombinant adeno-associated virus (AAV), which produced sustained inhibition of calcium current conducted by Ca V 3.2/T-type channels and significantly attenuated both evoked and spontaneous pain behavior in rats with neuropathic pain after tibial nerve injury. Recordings from dissociated sensory neurons showed that AAV-mediated Ca V 3.2iPA expression suppressed neuronal excitability, suggesting that Ca V 3.2iPA treatment attenuated pain by reversal of injury-induced neuronal hypersensitivity. Collectively, our results indicate that Ca V 3.2iPAs are promising analgesic leads that, combined with AAV-mediated delivery in anatomically targeted sensory ganglia, have the potential to be a selective peripheral Ca V 3.2-targeting strategy for clinical treatment of pain.
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Recent cross-sectional studies have identified differences in autobiographical memory (AM) among individuals with chronic pain, but the temporal relationship between the 2 is unknown. Moreover, AM has yet to be studied in patients undergoing major surgery. This study addressed these gaps by conducting a prospective, longitudinal study of memory performance, postsurgical pain, and psychosocial factors in 97 adult participants scheduled for major surgery. ⋯ Participants who took longer to recall pain memories before surgery (OR = 2.65, 95% CI [1.31-5.37]) and those who produced more surgery-related content at the one-month assessment (OR = 1.31, 95% CI [1.02-1.68]) had greater odds of reporting postsurgical pain up to 12 months later. These findings indicate that presurgical AM biases are risk factors for development and maintenance of postsurgical pain. To the extent that these biases are causal, presurgical interventions that modify the quality and content of patients' memories may prove to be promising strategies in the prevention of chronic postsurgical pain.