Pain
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Randomized Controlled Trial
Using eye movements to investigate selective attention in chronic daily headache.
Previous research has demonstrated that chronic pain is associated with biased processing of pain-related information. Most studies have examined this bias by measuring response latencies. The present study extended previous work by recording eye movement behaviour in individuals with chronic headache and in healthy controls while participants viewed a set of images (i.e., facial expressions) from 4 emotion categories (pain, angry, happy, neutral). ⋯ Both participant groups showed a significantly greater bias to maintain gaze longer on happy images, relative to pain, angry, and neutral images. Results are consistent with a pain-related bias that operates in the orienting of attention on pain-related stimuli, and suggest that chronic pain participants' attentional biases for pain-related information are evident even when other emotional stimuli are present. Pain-related information-processing biases appear to be a robust feature of chronic pain and may have an important role in the maintenance of the disorder.
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Human brain imaging investigations have revealed that acute pain is associated with coactivation of numerous brain regions, including the thalamus, somatosensory, insular, and cingulate cortices. Surprisingly, a similar set of brain structures is not activated in all chronic pain conditions, particularly chronic neuropathic pain, which is associated with almost exclusively decreased thalamic activity. These inconsistencies may reflect technical issues or fundamental differences in the processing of acute compared with chronic pain. ⋯ Neuropathic pain was associated with CBF decreases in a number of regions, including the thalamus and primary somatosensory and cerebellar cortices. In contrast, chronic nonneuropathic pain was associated with significant CBF increases in regions commonly associated with higher-order cognitive and emotional functions, such as the anterior cingulate and dorsolateral prefrontal cortices and the precuneus. Furthermore, in subjects with nonneuropathic pain, blood flow increased in motor-related regions as well as within the spinal trigeminal nucleus.
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Chronic neuropathic pain is often refractory to current pharmacotherapies. The rodent Mas-related G-protein-coupled receptor subtype C (MrgC) shares substantial homogeneity with its human homologue, MrgX1, and is located specifically in small-diameter dorsal root ganglion neurons. However, evidence regarding the role of MrgC in chronic pain conditions has been disparate and inconsistent. ⋯ Further, in a mouse model of trigeminal neuropathic pain, microinjection of JHU58 into ipsilateral subnucleus caudalis inhibited mechanical hypersensitivity in wild-type but not Mrg KO mice. Finally, JHU58 attenuated the miniature excitatory postsynaptic currents frequency both in medullary dorsal horn neurons of mice after trigeminal nerve injury and in lumbar spinal dorsal horn neurons of mice after SNL. We provide multiple lines of evidence that MrgC agonism at spinal but not peripheral sites may constitute a novel pain inhibitory mechanism that involves inhibition of peripheral excitatory inputs onto postsynaptic dorsal horn neurons in different rodent models of neuropathic pain.
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The α2δ-1 protein is an auxiliary subunit of voltage-gated calcium channels, critical for neurotransmitter release. It is upregulated in dorsal root ganglion (DRG) neurons following sensory nerve injury, and is also the therapeutic target of the gabapentinoid drugs, which are efficacious in both experimental and human neuropathic pain conditions. α2δ-1 has 3 spliced regions: A, B, and C. A and C are cassette exons, whereas B is introduced via an alternative 3' splice acceptor site. ⋯ Furthermore, this differential upregulation occurs preferentially in a small nonmyelinated DRG neuron fraction, obtained by density gradient separation. The α2δ-1 ΔA+BΔC splice variant supports CaV2 calcium currents with unaltered properties compared to α2δ-1 ΔA+B+C, but shows a significantly reduced affinity for gabapentin. This variant could therefore play a role in determining the efficacy of gabapentin in neuropathic pain.
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Pain relief by touch has been studied for decades in pain neuroscience. Human perceptual studies revealed analgesic effects of segmental tactile stimulation, as compared to extrasegmental touch. However, the spatial organisation of touch-pain interactions within a single human dermatome has not been investigated yet. ⋯ Touch also produced a bias to judge laser stimuli as less painful. This bias decreased linearly when the distance between the laser and tactile stimuli increased. Thus, our study provides evidence for a spatial organisation of intrasegmental touch-pain interactions.