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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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.
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Review Meta Analysis
Systematic review of movement-evoked pain versus pain at rest in postsurgical clinical trials and meta-analyses: a fundamental distinction requiring standardized measurement.
To estimate frequency of movement-evoked pain (MEP) measurement in human postsurgical investigations, we reviewed thoracotomy, knee arthroplasty, and hysterectomy clinical trials and meta-analyses. Only 39% of trials measured MEP and 52% failed to identify pain outcome as pain at rest (PAR) or MEP. Temporal trending did not suggest that MEP measurement is becoming more frequent. ⋯ This is an important problem because MEP is usually more severe than PAR; MEP exerts a more direct adverse impact on postsurgical functional recovery and several current and novel pain treatments differentially affect MEP vs PAR. Failure to distinguish between PAR and MEP and standardize their measurement threatens trial precision and ability to identify interventions with the most clinically relevant effects on pain. We therefore recommend developing consistent terminology regarding PAR and MEP, considering inclusion of MEP as a pain outcome in every postsurgical trial, and standardizing measurement of PAR and MEP on a procedure-specific basis.