Modulation of morphine analgesia in αCGRP mutant mice

Abstract

A homozygous CGRP−/− mouse line was generated by the targeted disruption of exon 5 in the calcitonin/αCGRP gene using homologous recombination. The mutant mice lack αCGRP mRNA. Furthermore CGRP immunoreactivity almost completely disappears from the spinal cord and is not at all observed in spinal ganglia and muscle synapses. However, motor end plates were still detected by acetylcholinesterase staining. Antinociceptive behavior tested by the tail flick and hot plate tests did not significantly differ in mutant and wild-type mice, except when challenged by morphine. Paradoxically, morphine analgesia was reduced in mutant mice compared with controls in the tail flick test, but not in the hot plate test. Thus, αCGRP differentially modulates opiate pain pathways.