Pentoxifylline reduces chronic post‐ischaemia pain by alleviating microvascular dysfunction

Background Microvascular dysfunction and ischaemia in muscle play a role in the development of cutaneous tactile allodynia in chronic post‐ischaemia pain ( CPIP ). Hence, studies were designed to assess whether pentoxifylline ( PTX ), a vasodilator and haemorrheologic agent, relieves allodynia in CPIP rats by alleviating microvascular dysfunction. Methods Laser D oppler flowmetry of plantar blood flow was used to examine the effects of PTX on CPIP ‐induced alterations in post‐occlusive reactive hyperaemia (reflecting microvascular dysfunction), and von F rey testing was used to examine its effects on CPIP ‐induced allodynia. Time‐course effects of PTX on allodynia and microvascular dysfunction were assessed early (2–8 days) and late (18–25 days) post‐ischaemia/reperfusion ( I/R ) injury, and its effects on allodynia were also tested at 30 days post‐ I/R injury. Results PTX (25 mg/kg) produced significant anti‐allodynic effects throughout the 21‐day time course, but was not effective 30 days post‐ I/R injury. In laser D oppler studies, the reduced reactive hyperaemia in early CPIP rats was significantly improved by PTX (25 mg/kg). Conversely, treatment with PTX at the same dose did not affect reactive hyperaemia in late CPIP rats, likely since reactive hyperaemia was not significantly reduced pre‐drug in these animals. Conclusion Since poor tissue perfusion underlies early stages of CPIP pain, the ameliorative effect of PTX on microvascular dysfunction might account for its anti‐allodynic effect in our experimental model of complex regional pain syndrome type I.