Articles: cations.
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Pain is a ubiquitous experience encompassing perceptual, autonomic, and motor responses. Expectancy is known to amplify the perceived and autonomic components of pain, but its effects on motor responses are poorly understood. Understanding expectancy modulation of corticospinal excitability has important implications regarding deployment of adaptive and maladaptive protective behaviours in anticipation of pain. ⋯ These results demonstrate that merely expecting pain influenced all pain components. Findings shed new light on the aetiology of expectancy-modulated pain, whereby expecting pain mobilises the motor system to protect the body from harm by a protective withdrawal reflex, associated with reduced corticospinal excitability, and activates similar processes as increased nociceptive stimulation. This has significant practical implications for the treatment of pain, particularly in scenarios where avoidance of pain-related movement contributes to its maintenance.
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Migraine affects ∼15% of the world's population greatly diminishing their quality of life. Current preventative treatments are effective in only a subset of migraine patients, and although cannabinoids seem beneficial in alleviating migraine symptoms, central nervous system side effects limit their widespread use. We developed peripherally restricted cannabinoids (PRCBs) that relieve chronic pain symptoms of cancer and neuropathies, without appreciable central nervous system side effects or tolerance development. ⋯ Peripherally restricted cannabinoid pretreatment prevented all behavioral and biochemical correlates of allodynia and latent sensitization. Importantly, long-term PRCB treatment alone did not produce any behavioral or biochemical signs of sensitization. These data validate peripheral cannabinoid receptors as potential therapeutic targets in migraine and medication overuse headache.