Pain
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Clinical evidence indicates that cognitive impairment is a common comorbid condition of chronic pain. However, the cellular basis for chronic pain-mediated cognitive impairment remains unclear. We report here that rats exhibited memory deficits after spared nerve injury (SNI). ⋯ Intracerebroventricular infusion of nocodazole, an MT destabilizer, ameliorated memory deficits in rats with SNI-induced nociceptive behavior. Expression of HDAC6, an α-tubulin deacetylase, was reduced in the hippocampus in rats with cognitive impairment. These findings indicate that peripheral nerve injury (eg, SNI) affects the MT dynamic equilibrium, which is critical to neuronal structure and synaptic plasticity.
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Randomized Controlled Trial Multicenter Study
Efficacy of the Nav1.7 blocker PF-05089771 in a randomised, placebo-controlled, double-blind clinical study in subjects with painful diabetic peripheral neuropathy.
The effect of PF-05089771, a selective, peripherally restricted Nav1.7 sodium channel blocker on pain due to diabetic peripheral neuropathy was investigated in a randomised, placebo and active-controlled parallel group clinical trial (NCT02215252). A 1-week placebo-run in the period was followed by a 4-week treatment period and a 1-week placebo run-out/taper-down period. Single-blind placebo was administered throughout run-in and run-out periods. ⋯ As predefined efficacy criteria were not met, the study did not proceed to the second part. PF-05089771 was well tolerated. Possible reasons for the modest efficacy observed with PF-05089771 are discussed.
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Pain significantly restricts the quality of life and well-being of older adults. With our increasingly ageing population, it is important to examine whether differing classes of biopsychosocial risk factors can predict the development of pain in older adults. Latent class analysis provides a model-based approach to identifying underlying subgroups in a population, based on some measured characteristics. ⋯ The High-Risk class was more likely to develop pain compared with the Low-Risk class (adjusted OR = 3.16, 95% CI = 2.40-4.16). These results add to existing data in other populations supporting the role of a range of biopsychosocial risk factors that increase the risk of developing pain. These findings have important implications for the identification, and potential moderation, of these risk factors.
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Expectations modulate the subjective experience of pain by increasing sensitivity to nociceptive inputs, an effect mediated by brain regions such as the insula. However, it is still unknown whether the neural structures underlying pain expectancy hold sensory-specific information or, alternatively, code for modality-independent features (eg, unpleasantness), potentially common with other negative experiences. We used functional magnetic resonance imaging to investigate neural activity underlying the expectation of different, but comparably unpleasant, pain and disgust. ⋯ At the brain level, this effect was mediated by the intermediate dysgranular section of the insula, whereas it was suppressed by more anterior agranular portions of the same region. Instead, no expectancy modulation was observed when the modality of the cue differed from that of the subsequent stimulus. Our data suggest that the insular cortex encodes prospective aversive events in terms of their modality-specific features, and whether they match with subsequent stimulations.