| First Author | De Logu F | Year | 2020 |
| Journal | Brain Behav Immun | Volume | 88 |
| Pages | 535-546 | PubMed ID | 32315759 |
| Mgi Jnum | J:314872 | Mgi Id | MGI:6819677 |
| Doi | 10.1016/j.bbi.2020.04.037 | Citation | De Logu F, et al. (2020) Macrophages and Schwann cell TRPA1 mediate chronic allodynia in a mouse model of complex regional pain syndrome type I. Brain Behav Immun 88:535-546 |
| abstractText | Complex regional pain syndrome type I (CRPS-I) is characterized by intractable chronic pain. Poor understanding of the underlying mechanisms of CRPS-I accounts for the current unsatisfactory treatment. Antioxidants and antagonists of the oxidative stress-sensitive channel, the transient receptor potential ankyrin 1 (TRPA1), have been found to attenuate acute nociception and delayed allodynia in models of CRPS-I, evoked by ischemia and reperfusion (I/R) of rodent hind limb (chronic post ischemia pain, CPIP). However, it is unknown how I/R may lead to chronic pain mediated by TRPA1. Here, we report that the prolonged (day 1-15) mechanical and cold allodynia in the hind limb of CPIP mice was attenuated permanently in Trpa1(-/-) mice and transiently after administration of TRPA1 antagonists (A-967079 and HC-030031) or an antioxidant (alpha-lipoic acid). Indomethacin treatment was, however, ineffective. We also found that I/R increased macrophage (F4/80(+) cell) number and oxidative stress markers, including 4-hydroxynonenal (4-HNE), in the injured tibial nerve. Macrophage-deleted MaFIA (Macrophage Fas-Induced Apoptosis) mice did not show I/R-evoked endoneurial cell infiltration, increased 4-HNE and mechanical and cold allodynia. Furthermore, Trpa1(-/-) mice did not show any increase in macrophage number and 4-HNE in the injured nerve trunk. Notably, in mice with selective deletion of Schwann cell TRPA1 (Plp1-Cre(ERT);Trpa1(fl/fl) mice), increases in macrophage infiltration, 4-HNE and mechanical and cold allodynia were attenuated. In the present mouse model of CRPS-I, we propose that the initial oxidative stress burst that follows reperfusion activates a feed forward mechanism that entails resident macrophages and Schwann cell TRPA1 of the injured tibial nerve to sustain chronic neuroinflammation and allodynia. Repeated treatment one hour before and for 3 days after I/R with a TRPA1 antagonist permanently protected CPIP mice against neuroinflammation and allodynia, indicating possible novel therapeutic strategies for CRPS-I. |
