Peroxisome proliferator-activated receptor-gamma agonist rosiglitazone attenuates postincisional pain by regulating macrophage polarization

Macrophage-specific nanotechnology-driven CD163 overexpression in human macrophages results in an M2 phenotype under inflammatory conditions

“…Inducing an efficient transition from M1 to M2 phenotype in macrophages by inducing CD163 as a gene therapy could directly restore a homeostatic state by targeting the cause of the problem. The induction of M2 macrophages has been shown to reduce pain-related behaviors in mice models of postoperative or neuropathic pain using a PPAR-γ agonist (Hasegawa-Moriyama, et al, 2012) or IL-4 (Kiguchi, et al, 2015). …”

“…Therefore, therapies that specifically target macrophages could result in the resolution of inflammation or pain. In fact, promoting an M2 phenotype has been shown to decrease pain-related behaviors in murine models of pain (Hasegawa-Moriyama, et al, 2012, Kiguchi, et al, 2015) This study focuses on exploring the functions of CD163 in human macrophages phenotype beyond its use as a phenotype marker. To our knowledge, the functional capabilities of CD163 in the acquisition of an M2 phenotype in macrophages have not been explored.…”

Pioglitazone Inhibits the Development of Hyperalgesia and Sensitization of Spinal Nociresponsive Neurons in Type 2 Diabetes

“…However, several studies suggest that pioglitazone can inhibit peripheral mechanisms of chronic pain: 1) PPARγ is expressed in sciatic nerve 110 ; 2) TZDs decreased hyperalgesia, proinflammatory cytokine expression, and macrophage infiltration in sciatic nerve after nerve injury 55, 96 ; 3) Pioglitazone reduced macrophage infiltration and pERK expression into the sciatic nerve of STZ rats 110 ; 4) Pioglitazone reduced pERK expression in sciatic nerve of db/db mice 15 ; and 5) Rosiglitazone and resolvin D1 coadministration to the site of hindpaw incision in db/db mice promotes a M2 macrophage phenotype and reduces mechanical hypersensitivity 82 . Future studies in preclinical models of type 2 PDN could investigate the effect of local TZD administration to the peripheral nerve 31, 96 on: macrophage polarization 31 ; TNFα, which is elevated in patients with PDN 74, 99 ; nerve conduction velocity, which is decreased in type 2 diabetes 6 ; and pain-like behaviors.…”

“…This is based on several lines of evidence. First, pioglitazone and other PPARγ agonists reduce neuropathic pain-like behavior in normoglycemic animals after various routes of administration including: repeated oral 55, 63 or intraperitoneal 31, 55, 63, 96 ; local injection to the injured sciatic nerve 96 or incised paw 31 ; or a single spinal 11, 30, 62, 71 or brain 62 injection. Second, numerous drugs can reduce PDN without reducing hyperglycemia in patients with PDN, including tapentadol 88 or the FDA-approved PDN medications duloxetine and pregabalin 59, 90 .…”

Macrophage development and polarization in chronic inflammation

“…The nuclear receptors PPAR␥ and PPAR␦ [45][46][47][48][49], for instance, control genes associated with M2 macrophage activation while induction of p50 nuclear factor kappa B (NF-B) homodimers is essential for M2 polarization in vitro and in vivo [50]. In addition, c-Jun N-terminal kinase (JNK) activation is required for M1 polarization of macrophages during obesity-induced inflammation and insulin resistance (IR) [51].…”