Opioids are broad spectrum
analgesics that are an integral part of the therapeutic armamentarium to combat
pain in the clinical practice. Unfortunately, together with
analgesia, a number of adverse effects can occur such as
nausea,
vomiting,
constipation, gastrointestinal alterations and
cognitive impairments.
Naltrexone is a competitive antagonist of
opioid receptors commonly used to treat
opioid addiction; its oral use against agonists side effects is limited by the decrease of
opioids-therapeutic efficacy and own adverse effects. The intranasal delivery of
naltrexone could offer a quick and effective achievement of CNS based on extracellular mechanisms including perineural and perivascular transport. The aim of the study was to test the efficacy of intranasal low-dose
naltrexone in reducing intraperitoneal
morphine and
oxycodone side effects in rodents. In mice, 1 μg
naltrexone intranasally administered 30 min before
opioids reduced
cognitive impairments and motor alteration induced by 10 mg kg-1
morphine and 60 mg kg-1
oxycodone in the Passive avoidance and Rota rod tests, respectively. Moreover,
naltrexone rebalanced
opioid-induced reduction of the intestinal transit and latency of feces expulsion as well as food intake inhibition. Importantly, 1 μg
naltrexone instillation did not block
analgesia as demonstrated by the Hot plate test. In rats, intranasal
naltrexone counteracted the
opioid-induced
pica phenomenon related to
emesis and increased water and palatable food intake. The effects were comparable to that achieved by
metoclopramide used as reference
drug. Treatments did not influence
body weight. Lastly, the safety of the intranasal delivery has been checked by
hematoxylin-
eosin staining that did not show histological alterations of the nasal cavity. In conclusion, intranasal low-dose
naltrexone counteracted
morphine and
oxycodone induced gastrointestinal and CNS side effects without impairing
opioid analgesia. It is a candidate to be a valid clinical strategy deserving deep analysis.