Pain
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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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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.
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Systemic artemin promotes regeneration of dorsal roots to the spinal cord after crush injury. However, it is unclear whether systemic artemin can also promote peripheral nerve regeneration, and functional recovery after partial lesions distal to the dorsal root ganglion (DRG) remains unknown. In the present investigation, male Sprague Dawley rats received axotomy, ligation, or crush of the L5 spinal nerve or sham surgery. ⋯ Sciatic and intradermal administration of dextran or cholera toxin B distal to the crush injury site resulted in labeling of neuronal profiles in the L5 DRG, suggesting regeneration functional restoration of nonmyelinated and myelinated fibers across the injury site into cutaneous tissue. Artemin also diminished ATF3 and caspase 3 expression in the L5 DRG, suggesting persistent neuroprotective actions. A limited period of artemin treatment elicits disease modification by promoting sensory reinnervation of distal territories and restoring preinjury sensory thresholds.
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The analgesic effect of heterotopic noxious counter-stimulation (HNCS; "pain inhibits pain") has been shown to decrease in older persons, while some neuropsychological studies have suggested a reduction in cognitive inhibition with normal aging. Taken together, these findings may reflect a generalized reduction in inhibitory processes. The present study assessed whether the decline in the efficacy of pain inhibition processes is associated with decreased cognitive inhibition in older persons. ⋯ Increased cognitive interference (ie, larger Stroop effect) correlated with smaller inhibition of the RIII reflex by HNCS across groups (r=-.34, P=0.025). This association was independent from the age-related slowing observed in control reading and naming tasks. These results suggest a generalized age-related reduction in inhibitory processes affecting both executive functions and cerebrospinal processes involved in the regulation of pain-related responses induced by competing nociceptive threats.