Review articleThalamus: The ‘promoter’ of endogenous modulation of pain and potential therapeutic target in pathological pain
Section snippets
Historic background and some unsolved scientific issues
Pain is an unpleasant sensory and emotional experience associated with, or resembling that associated with, actual or potential tissue damage (Raja et al., 2020). Internal and external noxious stimuli can evoke pain, which is accompanied by escapable behavior, i.e. nociceptive flexion reflex (also known as the nociceptive withdrawal reflex), followed by various physiological responses potentially associated with emotions (Besson and Chaouch, 1987, Millan, 1999). Pain has been proposed to be
Endogenous modulation of pain and its pathways
Currently, there is a wide consensus that nociceptive information ascending from the periphery to the cerebral cortex is controlled at various levels of the neuraxis by endogenous descending modulatory systems originating in multiple areas of the central nervous system (Millan, 2002, Pertovaara and Almeida, 2006). Among neural structures contributing to descending inhibition and/or facilitation of pain have been shown to be e.g. the cerebral cortex, thalamus, and various brain stem nuclei. The
Neurotransmitters in the thalamus-organized descending modulation of pain
Neurotransmitters involved in the thalamic MD nucleus and VM nucleus organized descending control of spinal nociception are summarized in Fig. 3.
Conclusion
Plastic changes in bottom-up mechanisms may not alone explain some important characteristics of clinical pain conditions, such as secondary (centrally mediated) pain sensitivity changes; i.e., hyperalgesia or hypoalgesia outside of the injury area. Instead, top-down mechanisms that include descending facilitation and descending inhibition provide plausible explanations for secondary hyperalgesia and hypoalgesia, respectively. A series of experimental studies has shown that one distinct
Conflict of interest statement
The authors declare no personal or financial conflicts of interest.
Acknowledgments
The present work was supported by grants from the National Natural Science Foundation of China (82074564, 81860410, 81772451, 81473752, 81271228). AP was supported by a grant from the Academy of Finland (315043).
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2022, Brain ResearchCitation Excerpt :These earlier findings on sex-dependent control of heat nociception in healthy animals are only partly similar with the present results on the sex-dependent control of mechanical hypersensitivity in neuropathic animals. The differences between the earlier (Lei et al., 2011) results on heat nociception under physiological conditions and the present results on mechanical hypersensitivity under neuropathic conditions may be explained by differences in the experimental conditions, since descending control of pain-related behavior has been shown to vary from facilitation to inhibition depending on the submodality of test stimulation and pathophysiological condition (Kauppila et al., 1998; You et al., 2022). In neuropathic animals of the present study, CeA inhibition disinhibited spinal α2-adrenoceptor-mediated suppression of ongoing-like behavior in a similar fashion in males and females, whereas spinal α2-adrenoceptors contributed to the suppression of mechanical hypersensitivity by CeA block in males rather than females.
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These authors contributed equally to this work