Effect of colitis on the involvement of serotonergic and nonserotonin neurons in the raphe nuclei nociceptive activation
DOI:
https://doi.org/10.33910/2687-1270-2024-5-3-307-317Keywords:
raphe nuclei, visceral pain, somatic pain, c-Fos expression, serotonergic neurons, colitisAbstract
The serotonin (5-HT)-synthesizing raphe magnus (RMg) and dorsal raphe (DR) nuclei are key pain processing centers. In addition to serotonergic nociceptive neurons, these regions house various non-serotonin cells that respond to pain stimuli. Our previous studies indicated that the RMg and DR contain distinct neuronal populations that specialize in either visceral or somatic nociception, with their activity being influenced by intestinal inflammation. However, the effects of inflammation on the general activation of the RMg and DR by visceral or somatic nociception and relative contribution of serotonergic and non-serotonergic mechanisms to this process remain unclear. In this immunohistochemical study performed on anesthetized male Wistar rats, we assessed colitis-induced changes in the neuronal activation of RMg and DR neurons by visceral (colorectal distension) and somatic (tail squeezing) pain stimuli, focusing on the local c-Fos-synthesizing activity and the balance between 5-HT-ergic and non-serotonin cells. Under normal conditions, non-serotonin neurons predominantly responded to visceral pain in both RMg and DR, whereas somatic nociception activated both 5HT-ergic and non-serotonin cells. Colitis led to a general increase in c-Fos production in RMg neurons, with their reduced response to somatic pain, and a decrease in c-Fos-positive DR neuron reactivity to both types of pain. These colitis-induced changes in the RMg were linked to a shift in somatic nociceptive processing toward greater involvement of non-serotonin neurons, while the DR maintained 5-HT-dependent pain signaling but exhibited reduced non-serotonin one. These neurochemical alterations associated with colitis may attenuate the RMg’s role in descending antinociceptive control and enhance nociceptive signaling from the DR to the forebrain, contributing to both visceral and somatic hyperalgesia.
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