Pentoxifylline attenuates the development of hyperalgesia in a rat model of neuropathic pain

Pentoxifylline attenuates nociceptive sensitization and cytokine expression in a tibia fracture rat model of complex regional pain syndrome

“…Laboratory investigations, however, generally employ the drug for its anticytokine effects and previous reports demonstrate that PTX administration virtually eliminates the up-regulation of cytokines in various pain models (Strieter et al 1988;Zabel et al 1993;Dorazil-Dudzik et al 2004;Ji et al 2004;Lu et al 2004;Vale et al 2004;Liu et al 2007). In this study we showed that chronic PTX treatment completely blocked fracture induced increases in hindpaw TNFα, IL-1β and IL-6 mRNA ( Fig.…”

“…To elaborate this hypothesis, we utilized the rat tibia fracture model seeking for changes in hindpaw cytokine expression after fracture and tested the therapeutic efficacy of chronic and acutely administered pentoxifylline (PTX), a phosphodiesterase inhibitor, which also has a broad-spectrum inhibitory effect on cytokine production (Strieter et al 1988;Zabel et al 1993;Dorazil-Dudzik et al 2004;Ji et al 2004;Lu et al 2004;Vale et al 2004;Liu et al 2007). …”

Minocycline modulates neuropathic pain behaviour and cortical M1–M2 microglial gene expression in a rat model of depression

“…Although minocycline is well-regarded as an inhibitor of microglial activation, recent evidence indicates that minocycline selectively inhibits microglial M1, but not M2, polarisation both in vitro and in an animal model of amyotrophic lateral sclerosis (Kobayashi et al, 2013). Previous studies have shown that antiinflammatory compounds (pentoxifylline, pioglitazone) attenuate neuropathic pain-related behaviour and related increases in M1 cytokines (TNFα, in the prefrontal cortex (Liu et al, 2007, Jia et al, 2010. This is the first study to examine if similar effects are observed with minocycline and reveal that chronic minocycline intake reduced the expression of CD11b, a marker of microglial activation, and the M1 cytokine IL-1β in sham-SNL rats.…”

Topical Combinations Aimed at Treating Microvascular Dysfunction Reduce Allodynia in Rat Models of CRPS-I and Neuropathic Pain

“…Pentoxifylline is a PDE4 inhibitor commonly used to treated these ischemic disorders 44,77 . A major metabolite of pentoxifylline, lisofylline shares many of the actions of its prodrug 60,61,90 , but also inhibits the conversion of lysophophatidic acid to phosphatidic acid (PA), a pathway critical to the production of various cytokines 76 .…”

“…Furthermore, these agents have neither been combined systemically, nor combined in topical preparations for the treatment of chronic pain. However, α 2A receptor agonists, NO donors and PDE inhibitors have been used systemically in patients or preclinical animal models to treat pain associated with angina 13,43,66 , PAD 19,52,82 , CRPS 18,40,63,74 , neuropathic pain 32,53,60 and PDN 16,24,48,84 indicating their usefulness in these syndromes. PA inhibitors have not been used to treat chronic pain, but should be equally or more effective than PDE inhibitors since they have anti-oxidant 7,34 , anticytokine 68,76 , anti-chemotaxic 70,91 , immunosuppressant 15,23 , and mitochondrial protective 12 effects, in addition to the vasodilator 61 , anti-ischemic 90 and anti-platelet aggregation 62 effects they share with PDE inhibitors.…”