Primary afferent neurons express functional delta opioid receptors in inflamed skin.
Peripherally-restricted opiate compounds attenuate hyperalgesia in experimental models of inflammatory pain, but have little discernable effect on nociceptive behavior in normal animals. This suggests that activation of opioid receptors on peripheral sensory axons contributes to decreased afferent activity after injury. Previously, we reported that direct application of morphine to cutaneous receptive fields decreased mechanical and heat-evoked responses in a population of C-fiber nociceptors in inflamed skin. Consistent with reported behavioral studies, direct application of morphine had no effect on fiber activity in control skin. The aim of the present study was to determine whether mechanical responsiveness of nociceptors innervating inflamed skin was attenuated by direct activation of delta opioid receptors (DORs) on peripheral terminals. An ex vivo preparation of rat plantar skin and tibial nerve was used to examine effects of a selective DOR agonist, deltorphin II, on responsiveness of single fibers innervating inflamed skin. Electrical recordings were made eighteen hours after injection of complete Freund's adjuvant into the hindpaw. Deltorphin II produced an inhibition of the mechanical responsiveness of single fibers innervating inflamed skin; an effect blocked by the DOR-selective antagonist, naltrindole. The population of units responsive to deltorphin II was identified as consisting of C fiber mechanical nociceptors.
Department of Pharmacology, University of Minnesota, Minneapolis, MN 55455, USA.
Jill-Desiree
JD
Brederson
Department of Neuroscience, University of Minnesota, Minneapolis, MN 55455, USA. Electronic address: cnhonda@umn.edu.
Christopher N
CN
Honda
D000200:Action Potentials / Q000187:drug effects / Q000502:physiology; D000704:Analysis of Variance; D000818:Animals; D004305:Dose-Response Relationship, Drug; D004558:Electric Stimulation; D005620:Freund's Adjuvant / Q000633:toxicity; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008297:Male; D009271:Naltrexone / Q000031:analogs & derivatives / Q000494:pharmacology; D009292:Narcotic Antagonists / Q000494:pharmacology; D009412:Nerve Fibers / Q000187:drug effects / Q000502:physiology; D009475:Neurons, Afferent / Q000187:drug effects / Q000378:metabolism*; D009842:Oligopeptides / Q000494:pharmacology; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000235:genetics / Q000378:metabolism*; D012867:Skin / Q000294:innervation*
D009292:Narcotic Antagonists; D009842:Oligopeptides; D017465:Receptors, Opioid, delta; C060209:deltorphin II, Ala(2)-; D009271:Naltrexone; D005620:Freund's Adjuvant; C055382:naltrindole
Deltorphin; Electrophysiology; Inflammation; Opiate; Peripheral; Periphery