Pain
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Randomized Controlled Trial
Perceptual bias in pain: A switch looks closer when it will relieve pain than when it won't.
Pain is fundamental to survival, as are our perceptions of the environment. It is often assumed that we see our world as a read-out of the sensory information that we receive; yet despite the same physical makeup of our surroundings, individuals perceive differently. What if we "see" our world differently when we experience pain? Until now, the causal effect of experimental pain on the perception of an external stimulus has not been investigated. ⋯ The critical result was a strong interaction between reaching and pain [F(1,181)=4.8, P=0.03], such that when participants experienced pain and were required to reach for a switch that would turn off the experimental stimulus, they judged the distance to that switch to be closer, as compared to the other 3 conditions (mean of the true distance 92.6%, 95% confidence interval 89.7%-95.6%). The judged distance was smaller than estimates in the other 3 conditions (mean±SD difference >5.7%±2.1%, t(181) >3.5, P<0.01 for all 3 comparisons). We conclude that the perception of distance to an object is modulated by the behavioural relevance of the object to ongoing pain.
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Ciguatera, the most common form of nonbacterial ichthyosarcotoxism, is caused by consumption of fish that have bioaccumulated the polyether sodium channel activator ciguatoxin. The neurological symptoms of ciguatera include distressing, often persistent sensory disturbances such as paraesthesias and the pathognomonic symptom of cold allodynia. We show that intracutaneous administration of ciguatoxin in humans elicits a pronounced axon-reflex flare and replicates cold allodynia. ⋯ To establish their in vivo efficacy, we used a novel animal model of ciguatoxin-induced cold allodynia. However, differences in the efficacy of these compounds to reverse ciguatoxin-induced cold allodynia did not correlate with their potency to inhibit ciguatoxin-induced responses in SH-SY5Y cells or at heterologously expressed Nav1.3, Nav1.6, Nav1.7, or Nav1.8, indicating cold allodynia might be more complex than simple activation of Nav channels. These findings highlight the need for suitable animal models to guide the empiric choice of analgesics, and suggest that lamotrigine and flupirtine could be potentially useful for the treatment of ciguatera.
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The perception of pain changes as people age. However, how aging affects the quality of pain and whether specific pain-processing brain regions mediate this effect is unclear. We hypothesized that specific structures in the cerebral nociceptive system mediate the effect of aging on the variation in different pain psychophysical measures. ⋯ The analyses of gray matter volume revealed that key nociceptive cerebral regions did not undergo significant age-related gray matter loss. However, the volume of the cingulate cortex covaried with pain perception after adjusting for corresponding neural activity to pain. These results suggest that age-related functional alterations in pain-processing regions are responsible for changes in pain perception during normal aging.
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Menthol, the cooling natural product of peppermint, is widely used in medicinal preparations for the relief of acute and inflammatory pain in sports injuries, arthritis, and other painful conditions. Menthol induces the sensation of cooling by activating TRPM8, an ion channel in cold-sensitive peripheral sensory neurons. Recent studies identified additional targets of menthol, including the irritant receptor, TRPA1, voltage-gated ion channels and neurotransmitter receptors. ⋯ L-menthol- and WS-12-induced analgesia was blocked by naloxone, suggesting activation of endogenous opioid-dependent analgesic pathways. Our data show that TRPM8 is the principal mediator of menthol-induced analgesia of acute and inflammatory pain. In contrast to menthol, selective TRPM8 agonists may produce analgesia more effectively, with diminished side effects.