title: Inflammation and hyperalgesia in rats neonatally treated with capsaicin: effects on two classes of nociceptive neurons in the superficial dorsal horn.
abstract: To address the mechanisms of hyperalgesia and dorsal horn plasticity following peripheral tissue inflammation, the effects of adjuvant-induced inflammation of the rat hindpaw on behavioral nociception and nociceptive neuronal activity in the superficial dorsal horn were examined in neonatally capsaicin-treated rats 6-8 weeks of age. Capsaicin treatment resulted in an 82% loss of unmyelinated fibers in L5 dorsal roots, a dramatic reduction of substance P-like immunoreactivity in the spinal cord, and a significant decrease in the percentage of dorsal horn nociceptive neurons that responded to C-fiber stimulation and noxious heating of the skin. The thermal nociceptive threshold was significantly increased in capsaicin-treated rats, but behavioral hyperalgesia to thermal stimuli still developed in response to inflammation. Following inflammation, there was a significant decrease in mechanical threshold and an increase in response duration to mechanical stimuli in both vehicle- and capsaicin-treated rats, suggesting that a state of mechanical hyperalgesia was also induced. The capsaicin treatment appears to have differential effects on nociceptive specific (NS) and wide-dynamic-range (WDR) neurons in inflamed rats. Expansion of the receptive fields of nociceptive neurons, a measure of the effect of inflammation-induced CNS plasticity, was less extensive for NS than for WDR neurons in capsaicin-treated rats. Compared to vehicle-treated rats, a smaller population of NS neurons, but a similar percentage of WDR neurons, had background activity in inflamed capsaicin-treated rats. C-fiber strength electrical stimulation of the sciatic nerve produced expansion of the receptive fields in a greater portion of NS neurons (53%, P < 0.05) in capsaicin- than in vehicle-treated rats (32%). There was no difference in stimulation-induced expansion of the receptive fields for WDR neurons between vehicle- or capsaicin-treated rats. An N-methyl-D-aspartate receptor antagonist, MK-801, attenuated the behavioral hyperalgesia and reduced the receptive field size of dorsal horn neurons in inflamed capsaicin- and vehicle-treated rats. The data suggest that while capsaicin-sensitive primary afferents may be involved in neuronal plasticity induced by peripheral tissue inflammation, changes in the capsaicin-insensitive WDR and NS populations are sufficient to produce thermal and mechanical hyperalgesia after the loss of capsaicin-sensitive primary afferents.
authors.affiliation: Neurobiology and Anesthesiology Branch, National Institute of Dental Research, National Institutes of Health, Bethesda, MD 20892 USA.
authors.forename: Ke
authors.initials: K
authors.lastname: Ren
authors.forename: Gene M
authors.initials: GM
authors.lastname: Williams
authors.forename: M A
authors.initials: MA
authors.lastname: Ruda
authors.forename: Ronald
authors.initials: R
authors.lastname: Dubner
mesh_terms: D000818:Animals; D000831:Animals, Newborn / Q000502:physiology*; D001522:Behavior, Animal / Q000502:physiology; D002211:Capsaicin; D016291:Dizocilpine Maleate / Q000494:pharmacology; D004558:Electric Stimulation; D005260:Female; D005620:Freund's Adjuvant; D006930:Hyperalgesia / Q000139:chemically induced / Q000473:pathology* / Q000523:psychology; D007150:Immunohistochemistry; D007249:Inflammation / Q000139:chemically induced / Q000473:pathology*; D008854:Microscopy, Electron; D009412:Nerve Fibers / Q000502:physiology / Q000648:ultrastructure; D009475:Neurons, Afferent / Q000187:drug effects / Q000502:physiology; D009619:Nociceptors / Q000502:physiology*; D010812:Physical Stimulation; D051381:Rats; D017207:Rats, Sprague-Dawley; D013116:Spinal Cord / Q000473:pathology / Q000502:physiology*
chemical_list: D016291:Dizocilpine Maleate; D005620:Freund's Adjuvant; D002211:Capsaicin