title: Fentanyl decreases discharges of C and A nociceptors to suprathreshold mechanical stimulation in chronic inflammation.
abstract: An essential component of mechanical hyperalgesia resulting from tissue injury is an enhanced excitability of nociceptive neurons, termed mechanical sensitization. Local application of opioids to inflamed rat paws attenuates mechanical hyperalgesia and reduces electrical excitability of C-fiber nociceptors in acute injury. Here, we examined the effects of the opioid receptor agonist fentanyl on the mechanical coding properties of not only C- but also A-fiber nociceptors innervating the rat hind paw in a model of chronic pain, i.e., 4 days after Freund's complete adjuvant-induced inflammation. The peripheral mechanosensitive terminals of C-fibers (n = 143), A-fibers (n = 79), and low-threshold mechanoreceptors (n = 25) were characterized using the in vitro skin-nerve preparation from the saphenous nerve. Although mechanical activation thresholds were not changed, discharges to suprathreshold mechanical stimuli were elevated significantly in both A- and C-fiber nociceptors from inflamed tissue. In addition, the proportion of nociceptors as well as the frequency of spontaneous discharges in A (14% vs. 0%)- and C (28% vs. 8%)-fibers were increased in inflamed compared with normal tissue. Fentanyl inhibited responses to suprathreshold stimuli in a significantly higher proportion of not only C (36% vs. 7%)- but also A (41% vs. 8%)-fibers in inflamed tissue in a naloxone-reversible and concentration-dependent manner. Our results demonstrate that mechanical sensitization persists in chronic inflammation, in correlation with behavioral hyperalgesia. Opioid sensitivity of both A- and C-fibers is markedly augmented. This is consistent with an upregulation or enhanced functionality of opioid receptors located at the peripheral terminals of sensitized nociceptors.
authors.affiliation: Department of Anesthesiology and Critical Care Medicine, Freie Universität Berlin, Charité Campus Benjamin Franklin, Berlin, Germany. rabih.moshourab@charite.de
authors.forename: Rabih
authors.initials: R
authors.lastname: Moshourab
authors.forename: Christoph
authors.initials: C
authors.lastname: Stein
mesh_terms: D000200:Action Potentials / Q000187:drug effects*; D000701:Analgesics, Opioid / Q000494:pharmacology*; D000818:Animals; D005283:Fentanyl / Q000494:pharmacology*; D005620:Freund's Adjuvant; D006614:Hindlimb; D007249:Inflammation / Q000139:chemically induced / Q000503:physiopathology*; D008297:Male; D008465:Mechanoreceptors / Q000145:classification / Q000187:drug effects; D009412:Nerve Fibers / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D051381:Rats; D017208:Rats, Wistar; D012684:Sensory Thresholds; D012867:Skin / Q000294:innervation; D014110:Touch
chemical_list: D000701:Analgesics, Opioid; D005620:Freund's Adjuvant; D005283:Fentanyl