Skip to main page content
U.S. flag

An official website of the United States government

Dot gov

The .gov means it’s official.
Federal government websites often end in .gov or .mil. Before sharing sensitive information, make sure you’re on a federal government site.

Https

The site is secure.
The https:// ensures that you are connecting to the official website and that any information you provide is encrypted and transmitted securely.

Access keys NCBI Homepage MyNCBI Homepage Main Content Main Navigation
. 1996 Nov;279(2):502-6.

Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance

Y A Kolesnikov  1 , S Jain, R Wilson, G W Pasternak
Affiliations
  • PMID: 8930151

Peripheral morphine analgesia: synergy with central sites and a target of morphine tolerance

Y A Kolesnikov et al. J Pharmacol Exp Ther. 1996 Nov.

Abstract

Morphine injected s.c. in the tail is a potent analgesic in the tail-flick assay when the radiant heat source is focused directly over the injection site (ED50, 4.5 micrograms), but not if the radiant heat source is moved 1 cm proximally or distally to the injection site. Naloxone given systemically reverses this peripheral analgesia. Antisense oligodeoxynucleotides directed against exons 1 and 4 of MOR-1, a cloned mu opioid receptor, administered intrathecally (i.t.) block the local analgesic effect of morphine in the tail, indicating that the local response is mediated through mu receptors located on the terminals of sensory neurons from the dorsal root ganglia. Combinations of morphine given locally in the tail and spinally (i.t.) are synergistic. Spinal morphine also synergizes with systemic morphine in analgesia assays. Supraspinal morphine enhances systemic morphine analgesia, but less dramatically. We also examined tolerance on these analgesic systems by using a daily morphine injection paradigm which shifts the dose-response curve for systemic morphine approximately 2-fold after 5 days. In this paradigm, morphine's analgesic potency after either supraspinal or spinal administration alone does not change. However, the dose-response curve for local morphine in the tail is shifted by over 19-fold. The analgesic activity of the combination of supraspinal and systemic morphine is lowered approximately 2-fold and the combination of i.t. and systemic morphine by 12-fold. These studies confirm the presence of a peripheral mechanism for morphine analgesia mediated by mu receptors located on sensory neurons from the dorsal root ganglia, which is extremely sensitive to chronic morphine dosing.

PubMed Disclaimer

Similar articles

See all similar articles

Cited by

See all "Cited by" articles

Publication types

LinkOut - more resources