Table 1.
Main findings of studies investigating changes in the BBB/BSCB associated with inflammatory pain.
| Barrier | Model | Main outcomes | Reference |
|---|---|---|---|
| BBB | Inflammatory pain, produced by subcutaneous injection of CFA, λ-carrageenan (CIP) or formalin, in sprague–dawley rats. | Peripheral inflammation led to an increase in the uptake of sucrose into the cerebral hemispheres, in all models studied. Western blot revealed changes in the TJ protein expression during peripheral inflammation. Occludin decreased in the groups treated with λ-carrageenan or CFA, while ZO-1 expression was increased in all inflammatory pain models. On the other hand, Claudin-1 protein expression did not change throughout the experiment. | Huber et al. (2001) |
| BBB | Chronic inflammatory pain, using CFA, in sprague–dawley rats. | Decrease in the expression of Occludin. Significant increase in the expression of claudin-3 (450%) and claudin-5 (615%) were also demonstrated, but the same results were not obtained with zonula occluden-1. | Brooks et al. (2005) |
| BBB | CIP, in sprague–dawley rats. | Increase in ICAM-1 RNA and protein expression in the thalamus, frontal, and parietal cortices; which were correlated with augmented expression of activated microglia. | Huber et al. (2006) |
| BBB | CIP and perineural injection of bupivacaine, in sprague–dawley rats. | Changes in the BBB integrity induced by CIP were prevented by a perineural injection of bupivacaine. This data suggests that nociceptive input is necessary to the increased BBB permeability found in λ–carrageenan models of inflammatory pain. | Campos et al. (2008) |
| BBB | CIP and capsaicin, in sprague–dawley rats. | Significant changes in occludin protein were observed in the lumbar spine after λ-carrageenan but not after capsaicin administration. Simultaneously, significant amounts of immunoglobulin G were seen in the lumbar and thoracic segments of the spinal cord | Xanthos et al. (2012) |
| BBB | CIP, in sprague–dawley rats. | Structural changes in P-gp. | McCaffrey et al. (2012) |
| BSCB | Perispinal inflammation induced by zymosan, in mice. | Perispinal inflammation led to changes in the reactivity of resident astrocytes and microglia within the spinal cord but maintained the integrity of the BSCB. Chronic pain did not develop. | Tenorio et al. (2013) |
| BBB | CIP and diclofenac treatment, in sprague-dawley rats. | Increased P-gp expression following peripheral inflammatory pain and also after diclofenac treatment. Both peripheral inflammatory pain and diclofenac treatment alone increased P-gp efflux activity, leading to a reduced morphine brain uptake. Analgesia produced by morphine was significantly reduced in animals pretreated with diclofenac, when compared to those that received diclofenac and morphine concurrently. | Sanchez-Covarrubias et al. (2014) |