Chronic dizocilpine or apomorphine and development of neuropathy in two rat models I: behavioral effects and role of nucleus accumbens.

Dopaminergic and glutamatergic inputs converge on nucleus accumbens (NAC) and affect the neuropathic pain. We tested the effects of daily systemic administration of dizocilpine (MK-801), a N-methyl-d-Aspartate (NMDA) noncompetitive receptor antagonist, or apomorphine (APO), a dopamine (DA) D1 and D2 receptor agonist, on neuropathic manifestations in the chronic constriction injury (CCI) and the spared nerve injury (SNI) models of mononeuropathy in rats. Six groups of rats were subjected to CCI or SNI neuropathy and 5-7 days later received daily intraperitoneal (ip) injections of saline, MK-801, or APO for two weeks. Tests for nociception and motor behaviors were performed at regular intervals. Tactile and cold allodynia were assessed using von Frey hairs or acetone drops, respectively. Heat hyperalgesia was assessed by the paw withdrawal test. Tests were performed before administering the daily injections. Another four groups of rats were subjected to SNI surgery, and then had their NAC (contralateral to the lesioned paw) perfused for two weeks with MK-801, saline, APO+ascorbic acid, or ascorbic acid alone using mini-osmotic pumps. Behavioral manifestations were assessed as above. Systemic daily injections of MK-801 and APO markedly attenuated the neuropathic manifestations in the CCI and SNI models with a minimal effect on cold allodynia. The same results were seen in the SNI model with chronic perfusion of NAC. Our results suggest that daily systemic administration of DA agonists and NMDA antagonists can attenuate neuropathic pain manifestations and that the NAC is involved in the modulation of neuropathic-like behaviors.