Analgesic effects of intraarterial injection of imipenem/cilastatin sodium in a rat model of knee osteoarthritis

Angiogenesis plays a role in the mechanism underlying musculoskeletal pain; thus, embolization of blood vessels may exert an analgesic effect. Recent clinical studies have reported promising therapeutic outcomes for arterial embolization in knee osteoarthritis (OA). However, the placebo effect in human studies cannot be ignored, underscoring the need for objective evidence to validate the analgesic effects. However, basic research data supporting this role are limited. Thus, we investigated the analgesic effect of intraarterial administration of imipenem/cilastatin sodium (IPM/CS) in a model of knee OA induced by monosodium iodoacetate (MIA) using Sprague-Dawley rats. First, we infused IPM/CS in the right femoral artery and investigated the knee joint mechanical pressure threshold using pressure application measurement (PAM). Next, the nociceptive signals originating from the knee were analyzed via the spontaneous excitatory postsynaptic current (sEPSC) recording within the neural cells in the dorsal spinal horn using the in vivo patch-clamp recording. In the model of knee OA, the mechanical thresholds at the damaged knee were decreased compared with those of the contralateral knee, whereas these thresholds remained stable in the sham group (p < 0.05). The pressure threshold of the model of knee OA was significantly increased following intraarterial infusion of IPM/CS but not saline (p < 0.05). A notable decrease in the average sEPSC frequency in the model of knee OA following intraarterial infusion of IPM/CS but not saline (p < 0.05). These results indicated that intraarterial infusion of IPM/CS attenuated nociception caused by knee OA.