Inflammasome Signaling Regulates the Microbial–Neuroimmune Axis and Visceral Pain in Mice

Interactions between the intestinal microbiota, immune system and nervous system are essential for homeostasis in the gut. Inflammasomes contribute to innate immunity and brain–gut interactions, but their role in microbiota–neuro–immune interactions is not clear. Therefore, we investigated the effect of the inflammasome on visceral pain and local and systemic neuroimmune responses after antibiotic-induced changes to the microbiota. Wild-type (WT) and caspase-1/11 deficient (Casp1 KO) mice were orally treated for 2 weeks with an antibiotic cocktail (Abx, Bacitracin A and Neomycin), followed by quantification of representative fecal commensals (by qPCR), cecal short chain fatty acids (by HPLC), pathways implicated in the gut–neuro-immune axis (by RT-qPCR, immunofluorescence staining, and flow cytometry) in addition to capsaicin-induced visceral pain responses. Abx-treatment in WT-mice resulted in an increase in colonic macrophages, central neuro-immune interactions, colonic inflammasome and nociceptive receptor gene expression and a reduction in capsaicin-induced visceral pain. In contrast, these responses were attenuated in Abx-treated Casp1 KO mice. Collectively, the data indicate an important role for the inflammasome pathway in functional and inflammatory gastrointestinal conditions where pain and alterations in microbiota composition are prominent.

Basophils getting on your nerves? Itching for clarity on flares in atopic dermatitis

Flares of acute itch in the setting of atopic dermatitis may engage a novel neuroimmune axis that includes basophils, LTC4, and sensory neurons.

Review of complex regional pain syndrome and the role of the neuroimmune axis

Background Complex regional pain syndrome (CRPS) is a progressive and painful disease of the extremities that is characterized by continuous pain inconsistent with the initial trauma. CRPS is caused by a multi-mechanism process that involves both the peripheral and central nervous system, with a prominent role of inflammation in CRPS pathophysiology. This review examines what is currently known about the CRPS inflammatory and pain mechanisms, as well as the possible impact of neurostimulation therapies on the neuroimmune axis of CRPS. Study design A narrative review of preclinical and clinical studies provided an overview of the pain and inflammatory mechanisms in CRPS and addressed the effect of neurostimulation on immunomodulation. Methods A systematic literature search was conducted based on the PRISMA guidelines between September 2015 to September 2020. Data sources included relevant literature identified through searches of PubMed, Embase and the Cochrane Database of Systematic Reviews. Results Sixteen preclinical and eight clinical studies were reviewed. Preclinical studies identified different mechanisms of pain development in the acute and chronic CRPS phases. Several preclinical and clinical studies investigating inflammatory mechanisms, autoimmunity, and genetic profiles in CRPS, supported a role of neuroinflammation in the pathophysiology of CRPS. The immunomodulatory effects of neurostimulation therapy is still unclear, despite clinical improvement in the CRPS patients. Conclusions Increasing evidence supports a role for inflammation and neuroinflammation in CRPS pathophysiology. Preliminary neurostimulation findings, together with the role of (neuro)inflammation in CRPS, seems to provide a compelling rationale for its use in CRPS pain treatment. The possible immunomodulatory effects of neurostimulation opens new therapeutic possibilities, however further research is needed to gain a better understanding of the working mechanisms.