Late transcriptional changes in blood, neural, and colon tissues in rat stress alone and comorbid pain model compared with naïve have regulatory roles in neurological disease

ABSTRACT: Purpose: Irritable bowel syndrome (IBS) and temporomandibular disorder (TMD) are two chronic pain conditions that frequently occur in the same individuals, most commonly women. Stress is the main risk factors associated; however, the mechanisms underlying IBS-TMD co-morbidity are mostly unknown Methods: Twenty-four female rats were randomly assigned to one of three experimental groups: naïve, stress-induced visceral hypersensitivity (SIH), and CPH (orofacial pain plus stress). RNA was extracted from blood, colon, spinal cord, and dorsal root ganglion after 1 or 7 weeks from the induction of stress. We combined differential gene expression and co-expression network analyses to define both SIH and CPH expression profiles across tissues and time Results: The transcriptomic profile in blood and colon showed increased expression of genes enriched in inflammatory and neurological biological processes in CPH compared to SIH rats, both at 1 and 7 weeks after stress. In lumbosacral spinal tissue, both SIH and CPH rats compared to naïve revealed decreased expression of genes related to synaptic activity and increased expression of genes enriched in “angiogenesis”, “Neurotrophin” and “PI3K-Akt” pathways. In DRG, CPH rats showed decreased expression of immune response genes at week1 and inhibition of nerve myelination genes at 7 weeks compared to naïve. For all tissues we observed higher expression of genes involved in ATP production in SIH compared to CPH at one week and this was reversed at seven weeks after the induction of stress. Compared to SIH, CPH rats showed increased expression of angiogenesis-related genes one week after exposure to stress, while 7 weeks post stress the expression of these genes was higher in SIH rats Conclusions: Our study highlights an increased inflammatory response in CPH compared to SIH rats in the blood and colon. DRG and spinal transcriptomic profiles of both CPH and SIH rats showed inhibition of synaptic activity along with activation of angiogenesis. Targeting these biological processes may lead to more profound understanding of the mechanisms underlying IBS-TMD comorbidities and new diagnostic and therapeutic strategies

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE199221 | GEO | 2022/05/31

REPOSITORIES: GEO