Pain
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To exert its analgesic action, paracetamol requires complex metabolism to produce a brain-specific lipoamino acid compound, AM404, which targets central transient receptor potential vanilloid receptors (TRPV1). Lipoamino acids are also known to induce analgesia through T-type calcium-channel inhibition (Ca(v)3.2). In this study we show that the antinociceptive effect of paracetamol in mice is lost when supraspinal Ca(v)3.2 channels are inhibited. ⋯ Interestingly, activation of TRPV1 induces a strong inhibition of Ca(v)3.2 current. Supporting this, intracerebroventricular administration of AM404 or capsaicin produces antinociception that is lost in Ca(v)3.2(-/-) mice. Our study, for the first time, (1) provides a molecular mechanism for the supraspinal antinociceptive effect of paracetamol; (2) identifies the relationship between TRPV1 and the Ca(v)3.2 channel; and (3) suggests supraspinal Ca(v)3.2 inhibition as a potential pharmacological strategy to alleviate pain.
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Botulinum Toxin B in the Sensory Afferent: Transmitter release, Spinal activation and Pain Behavior.
We addressed the hypothesis that intraplantar botulinum toxin B (rimabotulinumtoxin B: BoNT-B) has an early local effect upon peripheral afferent terminal releasing function and, over time, will be transported to the central terminals of the primary afferent. Once in the terminals it will cleave synaptic protein, block spinal afferent transmitter release, and thereby prevent spinal nociceptive excitation and behavior. ⋯ The observations following intrathecal SP offer evidence for a possible transsynaptic effect of intraplantar BoNT. These results provide robust evidence that peripheral BoNT-B can alter peripheral and central terminal release from a nociceptor and attenuate downstream nociceptive processing via a presynaptic effect, with further evidence suggesting a possible postsynaptic effect.
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The strength of the placebo effect is influenced by social contexts and individual personality. Although facial expressions provide important contextual cues, no study of their influence on the placebo response has been performed hitherto. Here we tested (1) whether the observation of facial expressions with different emotional content (Neutral, Pain, and Happy) affects the magnitude of placebo analgesia, and (2) whether interindividual differences in personality traits interact with any modulation of placebo response induced by facial expression. ⋯ In particular, a significantly greater analgesic effect was observed when facial expressions with emotional content were presented concomitantly to the nociceptive stimulation. The enhancement of placebo analgesia during the observation of facial expressions was not correlated with personality traits like empathy and behavioural activation/inhibition. These findings quantify for the first time the effect of facial expressions on the magnitude of placebo analgesia.