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VSL#3 protects against development of visceral pain in the neonatal maternal separation model: A whole genome microarray study

ABSTRACT: Background & Aims: Irritable bowel syndrome (IBS) is a disorder characterized by chronic abdominal pain and is linked to post-inflammatory and stress-correlated factors that cause changes in the perception of visceral events. Increased evidence indicates that probiotic bacteria may be useful in treating IBS. Our aims were to evaluate the efficacy of treatment with VSL#3, a mixture of 8 probiotic bacteria strains, in the neonatal maternal separation (NMS)-induced visceral hypersensitivity rat model and to determine whether it modulates the colonic expression of pain-related genes. Methods: Male NMS pups were treated orally with placebo or VSL#3 at days 3-60, while normal, not separated rats were used as control. After 60 days from birth, perception of painful sensation induced by colorectal distension (CRD) was measured by assessing the abdominal withdrawal reflex (score 0-4). The colonic gene expression analysis was assessed by using Agilent Whole Rat Genome Oligo Microarrays. Results: NMS rats exhibited both hyperalgesia and allodynia when compared with controls. VSL#3 showed a potent analgesic effect on CRD-induced pain without modifying colorectal compliance. The microarray analysis demonstrated that NMS rats had both over- and downregulation of several genes involved in inflammatory and painful processes and VSL#3 was able to counteract these alterations. Conclusions: This study indicates that VSL#3 is effective in reducing visceral pain in an experimental model of IBS by induction or suppression of pain-modulating genes. These observations provide support for the use of VSL#3 in the treatment of painful conditions related to IBS.

ORGANISM(S): Rattus norvegicus

PROVIDER: GSE38942 | GEO | 2013/06/26

SECONDARY ACCESSION(S): PRJNA169398

REPOSITORIES: GEO

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Project description: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

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VSL#3 protects against development of visceral pain in the neonatal maternal separation model: A whole genome microarray study

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