Bovine adrenal medulla 22 attenuates hyperalgesia in the early phase of complete Freund's adjuvant-induced inflammation in rats / 生理学报

ABSTRACT

The present study investigated the effects of intrathecal (i.t.) application of bovine adrenal medulla 22 (BAM22), an endogenous opioid peptide potently activating opioid receptors and sensory neuron-specific receptor (SNSR), on a model of complete Freund's adjuvant (CFA)-induced inflammatory pain. Unilateral, but not bilateral, inflammatory pain was induced by intraplantar (i.pl.) injection of CFA in one side, as indicated by the shortened paw withdrawal latency and the increased edema of paw. Paw withdrawal latency test, paw edema determination and immunohistochemistry were used in CFA-induced inflammatory pain model after i.t. administration of BAM22 or saline. It was found that administration of BAM22 dose-dependently attenuated CFA-induced hyperalgesia and edema, and resumed antinociceptive effects against thermal stimulation in behavioral test. In 10 nmol BAM22 group, paw withdrawal latency was resumed to 83.2% of normal, and edema increased only by 60% of normal at 48 h. The potency of BAM22 was 33.5% of maximal possible effect (MPE) at 24 h, and the antinociception persisted for at least 1 h. Furthermore, i.t. treatment of 10 nmol BAM22 evidently decreased the expressions of CFA-evoked neuronal nitric oxide synthase (nNOS)-positive cells and calcitonin gene-related peptide (CGRP)-immunoreactivity positive nerve fibers by 25.6% (P<0.01) and 25.2% (P<0.001) compared with saline group, respectively, at L3-L5 segments of the spinal cord. Small and medium CGRP-positive cells were 57.4% and 35.2% in dorsal root ganglion (DRG) in 10 nmol BAM22 group, respectively, which were remarkably lower than those in saline group (P<0.001). The present study suggests that BAM22 relieves CFA-induced thermal hyperalgesia in the early phase and resumes antinociceptive effects through down-regulation of nNOS and CGRP expressions in DRG and spinal cord, which is possibly mediated via SNSR.