The Effects Of Consecutive Activation Of Sensory Neuron-specific Receptor On The Potency Of Morphine Antinociception And Its Mechanism

The present studies were designed to investigate that the effects of consecutive activation of sensory neuron-specific receptor(SNSR)on potency of morphine antinociception and its mechanisms.The experiment first demonstrated that consecutive activation of SNSR by intrathecal(i.t.)administration of the specific agonist of SNSR BAM8-22 on potency of morphine antinociception which was revealed by the effects of morphin in formalin test.Then, we examined the hypothesis that activation of NMDA may be involved the effects of activation of SNSR on morphine's action.Lastly,we investigated molecul mechanisms.The present studies showed that following daily administration of BAM8-22 at a dose of 10 nmol for 6 days,i.t.morphine did not inhibit formalin-evoked nocifensive behaviours, expression of c-fos and NADPH-d neurons in the spinal cord and these responses were reversed by co-administration of AP-5,an NMDA receptor antagonist,with BAM8-22.Furthermore, chronic BAM8-22 induced significant increases in NADPH-d-positive neurons in the spinal cord and CGRP(Calcitonin-gene-related peptide)in dorsal root ganglia(DRG).The results in the current studies indicate that consective pharmacological stimulation of SNSR caused pontency of morphine antinociceptive,and this response was mediated via activation of NMDA receptors.Activation of NOS signal pathway in the spinal cord and increase of CGRP synthesis or/and release of CGRP in DRG underlined NMDA-mediated effects of activation of SNSR.