The ultra-short-acting
mu-opioid receptor (MOR) agonist
remifentanil enhances
postsurgical pain when used as main
anesthetic in animal models and man. Although the mechanism/s involved are poorly characterized, changes in
opioid receptor expression could be a relevant feature. Using a mouse model of
postoperative pain, we assessed the expression of MOR and
delta opioid receptors (DORs) and the efficacy of
Herpes Simplex vector-mediated
proenkephalin release (SHPE) preventing postoperative nociceptive sensitization induced by
remifentanil or
surgical incision. We determined MOR and DOR expressions in the dorsal root ganglia and the spinal cord after
remifentanil or surgery in CD1 mice, using real-time PCR and Western blotting. We also assessed the effect of SHPE on nociception induced by
remifentanil, surgery, and their combination (2 and 7 days after manipulation), using thermal and mechanical tests. Both
remifentanil and surgery decreased DOR
mRNA levels (up to days 2 and 4, respectively) in the dorsal root ganglia, but not in the spinal cord. No changes were observed in MOR
mRNA, or in receptor-
protein levels (Western) of either receptor. Pre-treatment with SHPE 7 days before manipulation prevented
remifentanil-induced
thermal hyperalgesia and
mechanical allodynia and the increase in incisional
pain observed when surgery was performed under
remifentanil anesthesia. SHPE also prevented surgically induced
allodynia but not
hyperalgesia, which was blocked by the additional administration of
RB101, an
enkephalinase inhibitor. The study suggests that down-regulation of DOR contributes to
remifentanil and surgery-induced nociception, and that
postoperative pain is completely reversed by increasing
enkephalin levels in the spinal cord and the periphery.