The Macrophage-Mediated Effects of the Peroxisome Proliferator-Activated Receptor-Gamma Agonist Rosiglitazone Attenuate Tactile Allodynia in the Early Phase of Neuropathic Pain Development

作者：Takahashi Yoshika; Hasegawa Moriyama Maiko^*; Sakurai Takashi; Inada Eiichi

来源：Anesthesia and Analgesia, 2011, 113(2): 398-404.

DOI：10.1213/ANE.0b013e31821b220c

BACKGROUND: Neuroinflammation triggered by macrophage infiltration into sites of peripheral nerve injury may result in neuropathic pain. Peroxisome proliferator-activated receptor (PPAR)gamma signaling regulates the properties of macrophages. However, the macrophage-mediated effects of PPAR gamma signaling on neuropathic pain triggered by peripheral inflammation have not been investigated.
METHODS: To evaluate the peripheral effects of PPAR gamma signaling on tactile allodynia, we administered the blood-brain barrier-impermeant PPAR gamma agonist, rosiglitazone, after partial sciatic nerve ligation (PSNL) as (1) systemic treatment during different phases of neuropathic pain development, (2) local injection to the PSNL site in the early phase, or (3) peritoneal macrophages pretreated with rosiglitazone transplanted into the PSNL site. In addition, the direct effect of rosiglitazone was evaluated in peritoneal macrophages activated with interferon-gamma.
RESULTS: Systemic rosiglitazone treatment early in the course of progressive inflammation ameliorated tactile allodynia, macrophage infiltration, and production of proinflammatory mediators including cyclooxygenase-2, inducible nitric oxide synthase, and matrix metalloprotease 9 at the PSNL site. Local injection of rosiglitazone and transplantation of rosiglitazone-treated peritoneal macrophages at the ligation site significantly improved tactile allodynia. In peritoneal macrophages, rosiglitazone down-regulated interferon-gamma gamma-induced gene expression of cyclooxygenase-2 and inducible nitric oxide synthase and attenuated the chemotactic response to monocyte chemotactic protein-1.
DISCUSSION: Rosiglitazone treatment in the early phase of neuropathic pain significantly alleviated the development of tactile allodynia by regulating macrophage infiltration and production of proinflammatory molecules at the inflamed site. Our results indicate that the activation of PPAR gamma signaling in macrophages during the early phase may suppress neuropathic pain development. (Anesth Analg 2011; 113: 398-404)

• 出版日期2011-8