Peripheral NMDA receptors are involved in long‐term hyperalgesia and spinal microglia activation induced by formalin injection

Abstract

Recent studies show that subcutaneous injection of formalin produce a long-term hyperalgesia (LTH), and a strong activation of spinal microglia lasting the similar period. This study is to investigate if peripheral NMDA receptors are involved in the formalin-induced LTH and the activation of spinal microglia by observing both behavioral responses examined by thermal paw withdrawal latency (PWL) and microglia activation examined by OX-42 immunocytochemistry. In PWL observations, rats received formalin injections of two hind paws, while MK-801 (30 nmol, n=5) was injected into one hind paw 15 min before formalin and the drug injections repeated in 4 consecutive days, respectively, and PWL observations were carried out for rats lasted 10 days. In OX-42 examinations, animals using the same trial of drug injections while three doses of MK-801 (10 nmol, 30 nmol, 50 nmol, n=5) was given rats and the animals killed 7 days post drug injections for OX-42 examinations. Results showed that: 1) peripheral formalin induced LTH examined by PWL which peaked at 7 days after formalin injection and lasted up to 2 weeks; 2) peripheral injection of formalin also induced long-term activation of microglia examined by OX-42 7 days post drug injections; 3) peripheral administration of MK-801 produced a significant suppression of the LTH; and 4) peripheral administration of MK-801 produced a significant and dose-dependent inhibition of microglia activation showing the 21.5%, 33.6%, 44.5% suppression of OX-42, respectively.