Pain
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The dorsal reticular nucleus (DRt) plays a key role in facilitation of nociceptive transmission at the spinal cord. In this study, we evaluated the mechanisms involved in GABA-mediated control of the DRt focusing on the role of local GABAB receptors. First, we used in vivo microdialysis to study the release of GABA in the DRt during the course of the formalin test. ⋯ For that purpose, we combined retrograde tract-tracing from the DRt with immunodetection of glutamate decarboxylase, the GABA-synthesizing enzyme. The higher numbers of retrogradely labelled glutamate decarboxylase-immunoreactive neurons were located at insular, somatosensory, and motor cortices. Collectively, the results suggest that GABA acting on GABAB receptors may enhance pain facilitation from the DRt during inflammatory pain.
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Moderate to severe chronic pain is a problem for 1.7 million children, costing $19.5 billion dollars annually in the United States alone. Risk-stratified care is known to improve outcomes in adults with chronic pain. However, no tool exists to stratify youth who present with pain complaints to appropriate interventions. ⋯ Risk groups did not significantly differ by pain diagnosis, location, or duration. Only 2% to 7% of patients who met reference standard case status for disability and emotional distress at 4-month follow-up were classified as low risk at baseline, whereas 71% to 79% of patients who met reference standard case status at follow-up were classified as high risk at baseline. A 9-item screening tool identifying factors associated with adverse outcomes among youth who present with pain complaints seems valid and provides risk stratification that can potentially guide effective pain treatment recommendations in the clinic setting.
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It is generally agreed that cold allodynia is a consequence of impaired (Aδ-fibre-mediated) central inhibition of C-nociceptive inputs. However, it is also known that C polymodal nociceptors are not activated at innocuous low temperatures. Recently, we demonstrated the contribution of C-tactile fibres to tactile allodynia. ⋯ Cold allodynia persisted after nerve compression and TRPV1 and TRPM8 desensitisation but was abolished by localised Cav3.2 blockade. In clinical subjects, C-fibre-mediated allodynia was observed without the need for experimental pain-producing manipulations. In conclusion, cold allodynia represents a non-TRPV1- and non-TRPM8-dependent phenomenon, which is mediated by low-threshold Cav3.2-expressing C fibres.
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Pain catastrophizing is associated with enhanced pain; however, the mechanisms by which it modulates pain are poorly understood. Evidence suggests that catastrophizing modulates supraspinal processing of pain but does not modulate spinal nociception (as assessed by nociceptive flexion reflex [NFR]). Unfortunately, most NFR studies have been correlational. ⋯ Although NFRs were not affected by the catastrophizing manipulation, temporal summation of NFR was reduced. However, this effect was not mediated by catastrophizing. These results indicate that reductions in catastrophizing lead to reductions in pain perception but do not modulate spinal nociception and provides further evidence that catastrophizing modulates pain at the supraspinal, not the spinal, level.
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According to fear-avoidance models, a catastrophic interpretation of a painful experience may give rise to pain-related fear and avoidance, leading to the development and maintenance of chronic pain problems in the long term. However, little is known about how exactly motivation and goal prioritization play a role in the development of pain-related fear. This study investigates these processes in healthy volunteers using an experimental context with multiple, competing goals. ⋯ However, during subsequent choice trials, participants selected the painful movement more often when the reward was presented compared with the context in which the reward was absent. The latter effect was dependent on goal prioritization, with more frequent selections in the reward-seeking group, and the least selections in the pain-avoidance group. Taken together, these results underscore the importance of competing goals and goal prioritization in the attenuation of avoidance behavior.