Pain
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Previous studies have established a bidirectional relationship between sleep and pain, and mood has been proposed as a mediator of this relationship. There are only a limited number of longitudinal studies examining the mediational role of mood, and the directionality of effects between sleep, pain, and mood is uncertain. In addition, despite the high prevalence of pain and sleep problems during adolescence, these relationships have rarely been examined in a longitudinal sample of adolescents. ⋯ Depressed mood and anxious mood mediated the effect of insomnia symptoms on pain, but not the reverse effect of pain on insomnia symptoms. Positive affect did not serve as a mediator in either direction. These findings add novel insights into the temporal directionality of sleep, pain, and mood during adolescence, suggesting a temporal path from sleep to pain, through mood, rather than a reciprocal relationship between the constructs.
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Although it is clear that osteoarthritis (OA) pain involves activation and/or sensitization of nociceptors that innervate knee joint articular tissues, much less is known about the role of the innervation of surrounding bone. In this study, we used monoiodoacetate (MIA)-induced OA in male rats to test the idea that pain in OA is driven by differential contributions from nerves that innervate knee joint articular tissues vs the surrounding bone. The time-course of pain behavior was assayed using the advanced dynamic weight-bearing device, and histopathology was examined using haematoxylin and eosin histology. ⋯ Changes in the function of bone afferent neurons were only observed at day 28, when there was histological evidence of damage to the articular cartilage and subchondral bone. Our findings suggest that pain early in MIA-induced OA involves activation and sensitization of nerves that innervate the joint capsule but not the underlying subchondral bone, and that pain in late MIA-induced OA involves the additional recruitment of nerves that innervate the subchondral bone. Thus, nerves that innervate bone should be considered important targets for development of mechanism-based therapies to treat pain in late OA.
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Data from the Global Burden of Disease Study 2019 were used to report the burden of migraine in 204 countries and territories during the period 1990 to 2019, through a systematic analysis of point prevalence, annual incidence, and years lived with disability (YLD). In 2019, the global age-standardised point prevalence and annual incidence rate of migraine were 14,107.3 (95% Uncertainty Interval [UI] 12,270.3-16,239) and 1142.5 (95% UI 995.9-1289.4) per 100,000, an increase of 1.7% (95% UI 0.7%-2.8%) and 2.1% (95% UI 1.1%-2.8%) since 1990, respectively. Moreover, the global age-standardised YLD rate in 2019 was 525.5 (95% UI 78.8-1194), an increase of 1.5% (95% UI -4.4% to 3.3%) since 1990. ⋯ Belgium (22,400.6 [95% UI: 19,305.2-26,215.8]), Italy (20,337.7 [95% UI: 17,724.7-23,405.8]), and Germany (19,436.4 [95% UI: 16,806.2-22,810.3]) had the 3 highest age-standardised point prevalence rates for migraine in 2019. In conclusion, there were large intercountry differences in the burden of migraine, and this burden increased significantly across the measurement period. These findings suggest that migraine care needs to be included within the health system to increase population awareness regarding the probable risk factors and treatment strategies especially among young adults and middle-aged women, as well as to increase the data on migraines.
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Normalization of the excitatory and inhibitory balance by increasing the levels of endogenous inhibitory neurotransmitters by blocking their reuptake is a promising therapeutic strategy for relieving chronic pain. Pharmacological blockade of spinal γ-aminobutyric acid (GABA) transporter subtypes 1 and 3 (GAT1 and GAT3) has been reported to generate analgesic effects in animal models of neuropathic pain. Here, we explored the synaptic mechanisms underlying their analgesic effects in the spinal dorsal horn. ⋯ These effects were antagonized by the GABAB receptor antagonist CGP55845. Consistently, the analgesic effect of intrathecally injected NNC-711 and SNAP-5114 in mice developing mechanical hypersensitivity after partial sciatic nerve ligation was abolished by CGP55845. Thus, GAT1 and GAT3 inhibitors exert distinct GABAB receptor-mediated inhibitory effects on excitatory synaptic transmission in the spinal dorsal horn, which most likely contributes to their analgesic effects.