探討大鼠之多巴胺 D2 型接受器調控脊髓反射增益現象

Abstract

Dopaminergic innervations on the spinal cord exhibit their inhibitory effect through the D2-like dopaminergic receptors (D2R)-dependent inhibition on protein kinase A (PKA). Recently, our laboratory reported a novel form of pain-related neural plasticity, the spinal reflex potentiation (SRP), which is presumed to underlie post-inflammatory hyperalgesia via PKA-dependent pathways. However, the effects of dopaminergic innervations on the SRP modulation have yet been established. In this study, we tried to determine the role of dopaminergic innervations in SRP and possible intracellular cascade involved using in vivo animal preparations. We recorded and analyzed the external urethra sphincter electromyography (EUSE) activity in response to repetitive stimulation (RS, 1 stimulation/sec) before and after intrathecal application of D2 agonist. We found that the intrathecal dopamine D2 agonist, Q110 (RS + Q), attenuated the RS-induced SRP that was reversed by pretreatment of L135, a dopamine D2 antagonist (RS + L + Q). Moreover, the glutamatergic receptor agonist, NMDA and AMPA agonist both antagonized the D2 agonist-elicited inhibition on SRP. Interestingly, when compared with AMPA agonist, NMDA exhibited a higher antagonistic effect of D2 agonist-elicited inhibition. In addiction, a PKA activator, forskolin, reversed D2 agonist-elicited inhibition on SRP. Together, these results suggest that dopaminerric innervations on the spinal cord might play roles in the modulation of SRP via D2R that is a possible target for the development of pharmacological strategies in the treatment of neuropathic pain.