Pain
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It is consistently reported that in inflammatory arthritis (IA), pain may continue despite well-controlled inflammation, most likely due to interactions between joint pathology and pain pathway alterations. Nervous system alterations have been described, but much remains to be understood about neuronal and central non-neuronal changes in IA. Using a rat model of IA induced by intra-articular complete Freund's adjuvant injection, this study includes a thorough characterization of joint pathology and objectives to identify peripheral innervation changes and alterations in the spinal dorsal horn (DH) that could alter DH excitatory balancing. ⋯ Here, we detected the presence of microgliosis and, interestingly, an apparent loss of inhibitory terminals and decreased expression of KCC2. In conclusion, we found evidence of anatomical, inflammatory, and neuronal alterations in the peripheral and central nervous systems in a model of IA. Together, these suggest that there may be a shift in the balance between incoming and outgoing excitation, and modulatory inhibitory tone in the DH.
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Activation of Aβ-fibers is fundamental to numerous analgesic therapies, yet its effects on dorsal horn neuronal activity remain unclear. We used multiphoton microscopy of the genetically encoded calcium indicator GCaMP6s to characterize the effects of Aβ-fiber electrical stimulation (Aβ-ES) on neural activity. Specifically, we quantified somatic responses evoked by C-fiber intensity stimulation before and after a 10-minute train of dorsal root Aβ-ES in superficial dorsal horn (SDH) neurons, in mouse lumbar spinal cord. ⋯ Aβ-ES effects on excitatory and inhibitory populations depended on the root used. Our findings suggest that Aβ-ES differentially modulates lumbar spinal cord SDH populations in a cell type- and input-specific manner. Furthermore, they underscore the importance of the Aβ-ES delivery site, suggesting that Aβ stimulation at a segment adjacent to where the pain is may improve analgesic efficacy.