Pain
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Human experimental studies have shown that levcromakalim, an ATP-sensitive potassium (KATP) channel opener, induces migraine attacks in people with migraine but not in healthy volunteers. However, the exact site of action for KATP channels in migraine pathophysiology remains unclear. This study investigates the role of these channels in the meninges in eliciting behavioral hypersensitivity responses in mice. ⋯ Finally, dural coinjection of glibenclamide inhibited periorbital hypersensitivity induced by CGRP or prolactin in female mice. These studies demonstrate that the meninges can be one site of action for the migraine-triggering effects of KATP channel openers. They also show that NO donors, CGRP, and prolactin can produce behavioral hypersensitivity through opening of KATP channels in the meninges.
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The thermal grill illusion (TGI), a phenomenon in which the juxtaposition of innocuous warm and cold temperatures on the skin elicits a burning sensation, offers a unique perspective to how pain occurs in response to harmless stimuli. We investigated the role of the spinal cord in the generation of the TGI across 2 experiments (total n = 80). We applied heat and cold stimuli to dermatomes, areas of skin innervated by a single spinal nerve, that mapped onto adjacent or nonadjacent spinal segments. ⋯ Perceived warmth and burning intensity increased when the cold stimulus projected to the segment more caudal to the warm stimulus, whereas perceived cold during the TGI decreased compared with the opposite spatial arrangement. This suggests that the perception of TGI is enhanced when cold afferents are projected to spinal segments positioned caudally in relation to those receiving warm afferents. Our results indicate distinct interaction of sensory pathways based on the segmental arrangement of afferent fibres and are consistent with current interpretations of the spread and integration of thermosensory information along the spinal cord.
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There is a limited understanding of risk factors and comorbidities in trigeminal neuralgia, a disease characterized by paroxysms of severe unilateral facial pain and a higher incidence in women. We aim to identify temporally associated comorbidities involving trigeminal neuralgia by analyzing nationwide disease trajectories. Using data from 7.2 million unique individuals in the Danish National Patient Register between 1994 and 2018, each individual diagnosed with trigeminal neuralgia was compared with 10,000 matched controls to identify co-occurring diseases. ⋯ Carbamazepine or oxcarbazepine treatment increased the ischemic stroke risk (hazard ratio 1.78; 95% confidence interval 1.47-2.17); however, the polygenic risk of stroke showed no association. In the Danish population, a trigeminal neuralgia diagnosis is temporally associated with 27 diseases revealed in systematic disease trajectories. Trigeminal neuralgia itself and its first-line treatment, but not a stroke polygenic risk score, was associated with an increased risk of ischemic stroke indicating that vascular risk factors should be routinely assessed in individuals with trigeminal neuralgia.
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Pain perception and its modulation are fundamental to human learning and adaptive behavior. This study investigated the hypothesis that pain perception is tied to pain's learning function. Thirty-one participants performed a threat conditioning task where certain cues were associated with a possibility of receiving a painful electric shock. ⋯ Prediction errors were also related to physiological nociceptive responses, including the amplitude of nociceptive flexion reflex and electroencephalography markers of cortical nociceptive processing (N1-P2-evoked potential and gamma-band power). In addition, higher pain expectations were related to increased late event-related potential responses and alpha/beta decreases in amplitude during cue presentation. These results further strengthen the idea of a crucial link between pain and learning and suggest that understanding the influence of learning mechanisms in pain modulation could help us understand when and why pain perception is modulated in health and disease.
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Empathy is characterized as the ability to share one's experience and is associated with altruism. Previous work using blood oxygen level-dependent (BOLD) functional MRI (fMRI) has found that empathy is associated with greater activation in brain mechanisms supporting mentalizing (temporoparietal junction), salience (anterior cingulate cortex; insula), and self-reference (medial prefrontal cortex; precuneus). However, BOLD fMRI has some limitations that may not reliably capture the tonic experience of empathy. ⋯ There was significantly (P = 0.01) higher empathy while viewing a romantic partner in pain and greater cerebral blood flow in the right temporoparietal junction, amygdala, anterior insula, orbitofrontal cortex, and precuneus when compared with the stranger. Higher empathy was associated with greater precuneus and primary visual cortical activation. The present findings indicate that brain mechanisms supporting the embodiment of another's experience is associated with higher empathy.