Identification of an <i>N</i>-acylated-^DArg-Leu-NH₂ Dipeptide as a Highly Selective Neuropeptide FF1 Receptor Antagonist That Potently Prevents Opioid-Induced Hyperalgesia

RF9, a potent and selective neuropeptide FF receptor antagonist, prevents opioid-induced tolerance associated with hyperalgesia.

Neuropeptide FF (NPFF) has been proposed to play a role in pain modulation, opioid tolerance, and several other physiological processes. However, pharmacological agents that would help define physiological roles for this peptide are still missing. Here we report the discovery of a potent and selective NPFF receptor antagonist, RF9, that can be administered systemically. This compound does not s...

A peripheral, intracerebral, or intrathecal administration of an opioid receptor antagonist blocks illness-induced hyperalgesia in the rat.

We used the tail-flick response of rats to study the role of opioid receptors in illness-induced hyperalgesia. An intraperitoneal injection of lithium chloride (LiCl) produced hyperalgesia that was blocked in a dose-dependent manner by subcutaneous injection of the opioid antagonist naloxone. Neither hyperalgesia nor its blockade by naloxone were due to variations in tail-skin temperature induc...

Opioid Induced Hyperalgesia

Opioid Induced Hyperalgesia

Opioid-induced hyperalgesia (OIH).

BACKGROUND AND OBJECTIVES Opioids are commonly used for pain control; however, they can cause hyperalgesia. The reason why this can happen is not known. The objective of this review was to describe the mechanisms, factors implicated, and drug modulation. CONTENTS The factors implicated in the development of opioid-induced hyperalgesia (OIH), such as duration of use, dose, and type of opioids ...