We studied whether striatal dopamine D2 receptors modulate pain in neuropathic rats. The tibial and the common peroneal nerves were ligated to produce a spared nerve injury (SNI) model of neuropathy. A chronic cannula was installed for microinjections of drugs into the striatum, and an intrathecal (i.t.) catheter for spinal drug administrations. Pain behavior was assessed by determining a withdrawal response to monofilaments and heating of the tail. Striatal administration of dopamine D2 receptor agonists (quinpirole or apomorphine) produced a suppression of mechanical hypersensitivity, and this effect was reversed by striatal administration of a D2 receptor antagonist (eticlopride). Dopamine D2 receptor agonists produced pain suppression also following i.t. administration, but the pain suppressive doses were ten times higher following spinal than striatal administration. The pain suppressive effect induced by a D2 receptor agonist in the striatum was attenuated by i.t. administration of an opioid receptor antagonist (naloxone) or a serotonin receptor antagonist (methysergide). The results indicate that striatal dopamine D2 receptors, via action on spinal serotonin and opioid receptors, suppress pain behavior in the SNI model of neuropathy.