Faculty Collaboration Database

The analgesic effects of supraspinal mu and delta opioid receptor agonists are potentiated during persistent inflammation. J Neurosci 2000 Feb 01;20(3):1249-59

Date

01/29/2000

Pubmed ID

10648729

Pubmed Central ID

PMC6774182

DOI

10.1523/JNEUROSCI.20-03-01249.2000

Scopus ID

2-s2.0-0034143366 (requires institutional sign-in at Scopus site)   183 Citations

Abstract

This study examined the antihyperalgesic and antinociceptive effects of opioid receptor agonists microinjected in the rostral ventromedial medulla (RVM) of rats 4 hr, 4 d, and 2 weeks after the induction of an inflammatory injury by injection of complete Freund's adjuvant (CFA) in one hindpaw. Nociceptive sensitivity of the ipsilateral, inflamed and the contralateral, uninflamed hindpaws was determined by the radiant-heat paw withdrawal test. The antihyperalgesic potency of the mu opioid receptor agonist [D-Ala(2),N-Me-Phe(4),Gly(5)-ol]enkephalin (DAMGO), determined for the inflamed hindpaw, was enhanced 4 d and 2 weeks after injury. The antinociceptive potency of DAMGO, determined for the contralateral, uninflamed hindpaw, was also progressively enhanced 4 hr, 4 d, and 2 weeks after injury. The magnitude of enhancement paralleled the chronicity of the injury. The greatest potentiation occurred 2 weeks after injury when the ED(50) value of DAMGO in CFA-treated rats was one-tenth that in saline-treated rats. The antihyperalgesic and antinociceptive effects of the delta opioid receptor agonist [D-Ala(2),Glu(4)]deltorphin were also increased 2 weeks after injury. These results indicate that peripheral inflammatory injury alters the pharmacology of excitatory and inhibitory inputs that modulate the activity of RVM neurons in such a manner as to enhance the effects of opioid agonists in this region. These changes have ramifications not only for the alleviation of hyperalgesia at the site of injury but also for opioid-induced antinociception at sites remote to the injury as revealed by increases in the potency of opioid agonists to suppress nociceptive responses of the contralateral, uninflamed hindpaw.

Author List

Hurley RW, Hammond DL

Author

Robert W. Hurley MD, PhD Adjunct Professor of Anesthesiology and CTSI in the Anesthesiology department at Medical College of Wisconsin

MESH terms used to index this publication - Major topics in bold

Analgesics, Opioid
Animals
Enkephalin, Ala(2)-MePhe(4)-Gly(5)-
Hindlimb
Hyperalgesia
Inflammation
Male
Medulla Oblongata
Microinjections
Nociceptors
Oligopeptides
Rats
Rats, Sprague-Dawley
Receptors, Opioid, delta
Receptors, Opioid, mu
Skin Temperature