Pentoxifylline reduces chronic post-ischaemia pain by alleviating microvascular dysfunction

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.

Laser Doppler 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 Frey 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.

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 Doppler 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.

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.