Supraspinal neuronal alterations promoting intestinal hyperalgesia in colitis
DOI:
https://doi.org/10.33910/2687-1270-2021-2-1-71-78Keywords:
intestinal inflammation, brainstem structures, c-fos expression, neuronal activity, colorectal distension, intestinal hyperalgesia, abdominal painAbstract
Inflammatory bowel diseases (Crohn’s disease, ulcerative colitis) are characterized by chronic abdominal pain that persists even in the disease remission. The main cause of such pain is believed to be intestinal hyperalgesia, which develops as a result of the peripheral inflammation-induced impairments in the central, in particular, supraspinal mechanisms controlling visceral nociception. However, which brain structures and neuronal events are involved in the process remains unclear. Our study was aimed to determine the colitis-associated changes in neuronal properties of supraspinal structures, which can underlie development of intestinal hyperalgesia. The work was performed on urethane anesthetized male Wistar rats. Neuronal activity in various brain areas was assessed in healthy animals and rats with trinitrobenzenesulfonic acid-induced colitis by using the immunohistochemical method of determining c-fos protein expression and the microelectrode technique. Intestinal inflammation was accompanied by increased basal and nociceptive colorectal distension (CRD)-caused c-fos production in the caudal ventrolateral medulla (CVLM), nucleus tractus solitarius (NTS), parabrachial complex, and locus coeruleus. Under colitis, neuronal c-fos expression in the dorsal raphe nucleus was indifferent to CRD, whereas nociceptive c-fos activation in the midbrain central gray (MCG) was significantly reduced compared to that in norm. The microelectrode study in inflamed rats revealed an increase in the CRD-induced CVLM and NTS neuronal excitation and a decrease in the proportion of CRD-responsive MCG cells. The observed colitis-associated sensitization of the viscerosensory brainstem areas with a simultaneous decrease in excitability of the key structures belonging to the brain antinociceptive system can facilitate ascending visceral pain transmission, promoting intestinal hyperalgesia.
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