Pain
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The transfer of nociceptive information at the level of dorsal horn is subject to extensive processing by both local segmental and supraspinal mechanisms, including descending dopaminergic controls, originating from the hypothalamic A11 nucleus. The inhibitory role of dopamine on evoked pain via activation of D2-like receptors at the level of the dorsal horn is well established. Here, by use of behavioral, electrophysiological, and anatomical techniques, we examined within the trigeminal sensory complex, first, whether descending dopaminergic controls also modulate pain behavior after an inflammatory insult, and second, under which physiological conditions these descending dopaminergic controls are actually recruited. ⋯ Altogether, our results are consistent with a tonic inhibition of the trigeminal nociceptive input by descending dopaminergic controls via activation of D2-like receptors at the level of superficial medullary dorsal horn. Such dopamine-dependent tonic inhibition of nociceptive information can be dynamically modulated by pain. This suggests that dysregulation of descending dopaminergic controls should translate in patients into diffuse, cephalic, and extracephalic pain symptoms--spontaneous pain, decreased pain thresholds, deficient DNIC, or some combination of these.
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Nucleotides contribute to the sensation of acute and chronic pain, but it remained enigmatic which G protein-coupled nucleotide (P2Y) receptors and associated signaling cascades are involved. To resolve this issue, nucleotides were applied to dorsal root ganglion neurons under current- and voltage-clamp. Adenosine triphosphate (ATP), adenosine diphosphate (ADP), and uridine triphosphate (UTP), but not uridine diphosphate (UDP), depolarized the neurons and enhanced action potential firing in response to current injections. ⋯ The facilitation of TRPV(1), but not the inhibition K(V)7 channels, was prevented by a protein kinase C inhibitor. Simultaneous blockage of K(V)7 channels and of TRPV(1) channels prevented nucleotide-induced membrane depolarization and action potential firing. Thus, P2Y(1) and P2Y(2) receptors mediate an excitation of dorsal root ganglion neurons by nucleotides through the inhibition of K(V)7 channels and the facilitation of TRPV(1) channels via a common bifurcated signaling pathway relying on an increase in intracellular Ca(2+) and an activation of protein kinase C, respectively.
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Multicenter Study
Multinomial logistic regression analysis for differentiating 3 treatment outcome trajectory groups for headache-associated disability.
Growth mixture modeling (GMM) identified latent groups based on treatment outcome trajectories of headache disability measures in patients in headache subspecialty treatment clinics. Using a longitudinal design, 219 patients in headache subspecialty clinics in 4 large cities throughout Ohio provided data on their headache disability at pretreatment and 3 follow-up assessments. ⋯ Three-fourths of patients who initiated treatment with elevated disability levels did not report reductions in disability after 5 months of treatment with new preventive pharmacotherapies. Preventive headache agents may be most efficacious for patients with moderate levels of disability and for patients with high disability levels who attend all treatment appointments.
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The magnitude of placebo response and its predictors in fibromyalgia syndrome (FMS) and painful peripheral diabetic neuropathy (DPN) had not been studied. We performed a systematic review by searching MEDLINE, CENTRAL, SCOPUS, and the databases of the U. S. ⋯ Placebo accounted for 45% of the response in the drug groups in FMS and for 62% in painful DPN. The placebo response was higher in painful DPN than in FMS (P<.001). The placebo response was not associated with age, sex, and race, but with year of study initiation, pain baseline, and effect size in active drug groups in both diseases.