Effects of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) administration to mice on nociceptive threshold to thermal and mechanical noxious stimuli

Abstract

Pain is one of non-motor symptoms (NMS) in Parkinsons disease (PD). However, it has not been well studied in rodent PD models. We used 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) intoxicated mouse model of PD to analyze the relationship between mechanical and thermal pain behavioral changes and degeneration of dopaminergic neurons caused by acute MPTP protocol: 4 times 20 mg MPTP/kg intraperitoneal (i.p.) injection with 2h intervals. MPTP-induced degenerating cell bodies and fibers were observed in the substantia nigra pars compacta (SNpc) and basal ganglia, especially in the striatum. Rotarod and round chamber testing were performed to confirm the motor dysfunction in MPTP treated mice. The latency to fall off the rod and the distance moved in round chamber was significantly reduced in intoxicated mice. MPTP treated mice showed significantly shorter nociceptive response latency both under pain, inflammatory pain induced by Complete Freunds adjuvant (CFA), and no pain condition compared to saline treated mice. MPTP-induced dopaminergic neuronal degeneration caused hyperalgesia in mice. We observed the partial rescue of hyperalgesia with subcutaneous injection, not i.p. injection of L-3,4-dihydroxyphenylalanine (L-DOPA). These results suggest that the dopaminergic nigrostriatal pathway has a role in inhibiting the noxious stimuli and L-DOPA potentially has an antinociceptive effect on PD.