Pain
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Dry eye disease (DED) affects >10% of the population worldwide, and it provokes an unpleasant sensation of ocular dryness, whose underlying neural mechanisms remain unknown. Removal of the main lachrymal gland in guinea pigs caused long-term reduction of basal tearing accompanied by changes in the architecture and density of subbasal corneal nerves and epithelial terminals. After 4 weeks, ongoing impulse activity and responses to cooling of corneal cold thermoreceptor endings were enhanced. ⋯ In healthy humans, exposure of the eye surface to menthol vapors or to cold air currents evoked unpleasant sensations accompanied by increased blinking frequency that we attributed to cold thermoreceptor stimulation. Notably, stimulation with menthol reduced the ongoing background discomfort of patients with DED, conceivably due to use-dependent inactivation of cold thermoreceptors. Together, these data indicate that cold thermoreceptors contribute importantly to the detection and signaling of ocular surface wetness, and develop under chronic eye dryness conditions an injury-evoked neuropathic firing that seems to underlie the unpleasant sensations experienced by patients with DED.
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The full role of adult hippocampal neurogenesis (AHN) remains to be determined, yet it is implicated in learning and emotional functions, and is disrupted in negative mood disorders. Recent evidence indicates that AHN is decreased in persistent pain consistent with the idea that chronic pain is a major stressor, associated with negative moods and abnormal memories. Yet, the role of AHN in development of persistent pain has remained unexplored. ⋯ Downregulating neurogenesis reversibly diminished or blocked persistent pain; oppositely, upregulating neurogenesis led to prolonged persistent pain. Moreover, we could dissociate negative mood from persistent pain. These results suggest that AHN-mediated hippocampal learning mechanisms are involved in the emergence of persistent pain.
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Randomized Controlled Trial
Cell cycle inhibition limits development and maintenance of neuropathic pain following spinal cord injury.
Chronic pain after spinal cord injury (SCI) may present as hyperalgesia, allodynia, and/or spontaneous pain and is often resistant to conventional pain medications. Identifying more effective interventions to manage SCI pain requires improved understanding of the pathophysiological mechanisms involved. Cell cycle activation (CCA) has been implicated as a key pathophysiological event following SCI. ⋯ Early administration of flavopiridol significantly shortened duration of MGS changes. Late flavopiridol intervention significantly limited hyperesthesia at 7 days after treatment, associated with reduced glial changes, but without effect on locomotion. Thus, our data suggest that cell cycle modulation may provide an effective therapeutic strategy to reduce hyperesthesia after SCI, with a prolonged therapeutic window.
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Pain can be modulated by contextual stimuli, such as emotions, social factors, or specific bodily perceptions. We presented painful laser stimuli together with body-related masochistic visual stimuli to persons with and without preferred masochistic sexual behavior and used neutral, positive, and negative pictures with and without painful stimuli as control. Masochists reported substantially reduced pain intensity and unpleasantness in the masochistic context compared with controls but had unaltered pain perception in the other conditions. ⋯ Masochists additionally showed negative correlations between the duration of interest in masochistic activities and activation of areas involved in motor activity and affective processing. We propose that the parietal operculum serves as an important relay station that attenuates the affective-motivational aspects of pain in masochists. This novel mechanism of pain modulation might be related to multisensory integration and has important implications for the assessment and treatment of pain.
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Adolescents who experience pain often face competing goals and have to choose whether to approach (confront) or avoid pain. This study investigates the decisions adolescents make when their pain conflicts with a valued goal. Adolescents between the ages of 15 and 18 years (N = 170) completed questionnaires on general and pain-specific anxiety, courage, and dispositional avoidance. ⋯ In addition, we compared approach-avoidance of adolescents with and without chronic pain; analyses revealed no differences in approach-avoidance behaviour. We also found that behavioural endurance was predictive of approach and dispositional avoidance predicted higher avoidance, but courage was not predictive of behaviour in this task. We adopt a motivational perspective when interpreting the findings and consider whether the fear-avoidance model should be extended to include the function of avoidance or approach in the pursuit of a desired goal.