Local versus Systemic Endomorphin 2 in a Carrageenan Model of Inflammatory Hyperalgesia

Infl ammation eff ectively increases the activation of opioid receptors on peripheral terminals of sensory neurons. Th e resulting infl ammatory hyperalgesia responds to local treatment with opioid analgesics by decreasing its intensity. Comparatively, much less is known about the effi ciency of opioid peptides administered peripherally at the infl ammation site. Th e study examined the antihyperalgesia elicited by endomorphin 2, a miu agonist, when administered peripherally in a model of acute infl ammation with carrageenan. Th e eff ects of locally administered endomorphin 2 in three diff erent doses were investigated with behavioral assays. Th e local paw injection of endomorphin at the site of infl ammation induced an antihyperalgesic eff ect. For confi rmation of the peripheral mechanism of analgesia, the peptide was systemically administered (i.p.) and at the dosage we used, endomorphin 2 was not signifi cantly antihyperalgesic. Endomorphin 2 was antihyperalgesic without signifi cantly aff ecting edema. In conclusion, the antihyperalgesic eff ect of the endomorphin 2 is not secondary to a reduction of edema, since reduction of edema does not occur. Th ese observations plead for an action at the level of opioid receptors on nerve terminals rather than on immune cells.