PubMed · 8080509
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M J Tobin. 1994-04-14. Mechanical ventilation.. https://doi.org/10.1056/nejm199404143301507
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OBJECTIVE: To determine the association between subjective and objective variables commonly used to evaluate severity of postoperative pain in dogs. DESIGN: Prospective double-blind study. ANIMALS: 36 dogs with unilateral rupture of the cranial cruciate ligament that underwent surgery to stabilize the stifle. PROCEDURE: Each dog was assessed to determine severity of pain before and after surgery, using various subjective and objective criteria. RESULTS: Subjective measures of pain (scores for visual analogue and numerical rating scales) correlated poorly or were not correlated with heart rate, respiratory rate, blood pressure, and results of a pain threshold test. Scores for visual analogue and numerical rating scales correlated with each other and with the amount of vocalization at most time periods. CLINICAL IMPLICATIONS: We detected a weak association between commonly employed subjective and objective measures of pain. This indicated that some of these measurement techniques do not predictably reflect severity of postoperative pain in dogs. Therefore, clinicians should not rely too heavily on these variables when assessing severity of postoperative pain in dogs.
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Repeated peripheral administration of the micro-opioid agonist [D-Ala2,N-Me-Phe4,gly5-ol] enkephalin (DAMGO) produces acute tolerance and dependence on its peripheral antinociceptive effect against prostaglandin E2 (PGE2)-induced mechanical hyperalgesia. In this study we evaluated the roles of protein kinase C (PKC) and nitric oxide (NO) in the development of this tolerance and dependence. Repeated administration of PKC inhibitors chelerythrine and 1-(5-isoquinolinesulfonyl)-2-methylpiperazine dihydrochloride with DAMGO did not alter the tolerance to DAMGO; however, dependence (defined as naloxone-induced withdrawal hyperalgesia) was blocked. Repeated administration of N-(n-heptyl)-5-chloro-1-naphthalenesulfonamide, a PKC activator, which alone did not produce tolerance, mimicked the dependence produced by DAMGO. Repeated administration of the NO synthase inhibitor NG-methyl-L-arginine with DAMGO blocked the development of tolerance to DAMGO but had no effect on the development of dependence. Repeated administration of L-arginine, a NO precursor, mimicked tolerance produced by repeated administration of DAMGO (i.e. , the antinociceptive effect of DAMGO was lost); however, L-arginine did not mimic dependence. These findings suggest that the development of acute tolerance and dependence on the peripheral antinociceptive effects of DAMGO have different, dissociable mechanisms. Specifically, PKC is involved in development of mu-opioid dependence, whereas the NO signaling system is involved in the development of mu-opioid tolerance.