Dynorphin expression and Fos-like immunoreactivity following inflammation induced hyperalgesia are colocalized in spinal cord neurons

Noguchi, Koichi; Kowalski, Krzysztof E.; Traub, Richard J.; Solodkin, Ana; Iadarola, Michael J.; Ruda, M.A.

doi:10.1016/0169-328x(91)90065-6

Cited by 215 publications

(80 citation statements)

References 28 publications

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“…In good accordance with numerous previous studies (Draisci & Iadarola, 1989;Noguchi et al, 1991Noguchi et al, , 1992; see and references therein; an intraplantar injection of carrageenan evoked a peripheral oedema and c-Fos protein expression in the spinal cord ipsilateral to the carrageenan-in¯amed hind paw in awake rats. Three hours after intraplantar carrageenan, two parameters of peripheral oedema, paw and ankle diameters, in carrageenan control rats (see results for experimental series I ± V in Table 1) were signi®cantly increased as compared to non-stimulated rats (0.48+0.02 and 0.75+0.03 cm for paw and ankle diameters, respectively).…”

Section: Resultssupporting

confidence: 73%

“…In agreement with previous studies (Draisci & Iadarola, 1989;Noguchi et al, 1991Noguchi et al, , 1992HonoreÂ et al, 1995;Buritova et al, 1996a and references therein), 3 h after intraplantar carrageenan, c-Fos-LI neurons were numerous in the super®cial (I ± II) and deeper (V ± VI) laminae of the L4 ± L5 segments of lumbar spinal cord in awake rats. This localization is in concordance with the spinal areas containing neurons activated by noxious stimuli driven by C-and Ad-®bres (see Besson & Chaouch, 1987;Willis & Coggeshall, 1991).…”

Section: Discussionsupporting

confidence: 78%

“…or 100 mg in 50 ml intraplantar, n=2 rats for each group), the cFos-LI neurons were virtually absent in lumbar spinal cord (53 c-Fos-LI neurons per section in segments L4 ± L5). These observations are in accordance with our previous results (HonoreÂ et al, 1995;Chapman et al, 1996) showing negligible spinal c-Fos protein expression after intraplantar injection of saline (55 c-Fos-LI neurons per section L4 ± L5) which was not signi®cantly di erent from that observed in non-stimulated rats.Peripheral oedema and c-Fos protein expression in the lumbar spinal cord at 3 h after intraplantar carrageenanIn good accordance with numerous previous studies (Draisci & Iadarola, 1989;Noguchi et al, 1991Noguchi et al, , 1992 see Buritova & Besson, 1998 and references therein; an intraplantar injection of carrageenan evoked a peripheral oedema and c-Fos protein expression in the spinal cord ipsilateral to the carrageenan-in¯amed hind paw in awake rats. Three hours after intraplantar carrageenan, two parameters of peripheral oedema, paw and ankle diameters, in carrageenan control rats (see results for experimental series I ± V in Table 1) were signi®cantly increased as compared to non-stimulated rats (0.48+0.02 and 0.75+0.03 cm for paw and ankle diameters, respectively).…”

supporting

confidence: 74%

“…These two experimental approaches were performed simultaneously in the same rat with acute in¯amma-tion evoked by an intraplantar injection of carrageenan. Intraplantar carrageenan induces an in¯ammatory oedema (Winter et al, 1962;Di Rosa et al, 1971 and references therein) associated with mechanical allodynia (Kayser & Guilbaud, 1987), heat and mechanical hyperalgesia (Hargreaves et al, 1988;Iadarola et al, 1988;Joris et al, 1990 and the expression of c-Fos protein at the spinal cord level (Draisci & Iadarola, 1989;Noguchi et al, 1991Noguchi et al, , 1992HonoreÂ et al, 1995). The expression of the nuclear protein c-Fos encoded by the immediate-early gene c-fos (for review see Morgan, 1991;Hughes & Dragunow, 1995;Morgan & Curran, 1995) is widely used as an indirect marker of neurons involved in spinal nociceptive processes (for review see Zieglgansberger & ToÈ lle, 1993;Munglani & Hunt, 1995;Chapman & Besson, 1997).…”

Section: Introductionmentioning

confidence: 99%

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Peripheral and/or central effects of racemic‐, S(+)‐ and R(−)‐flurbiprofen on inflammatory nociceptive processes: a c‐Fos protein study in the rat spinal cord

Buritova

Besson

1998

British J Pharmacology

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1 We have evaluated the e ects of intravenous or intraplantar racemic-, S(+)-and R(7)-¯urbiprofen on both the carrageenan-evoked peripheral oedema and spinal c-Fos immunoreactivity, an indirect index of neurons involved in spinal nociceptive processes. 2 Three hours after intraplantar injection of carrageenan (6 mg in 150 ml of saline) in awake rats, a peripheral oedema and numerous c-Fos protein-like immunoreactive (c-Fos-LI) neurons in L4 ± L5 segments were observed. c-Fos-LI neurons were essentially located in the super®cial (I ± II) and deep (V ± VI) laminae of the dorsal horn. 3 Intravenous racemic-¯urbiprofen (0.3, 3 and 9 mg kg 71 ) dose-relatedly reduced the carrageenanevoked oedema and spinal c-Fos expression (r=0.64, r=0.88 and r=0.84 for paw diameter, ankle diameter and number of c-Fos-LI neurons; P50.05, P50.001 and P50.001 respectively).4 Similar e ects to those of intravenous racemic-¯urbiprofen were obtained with intravenous S(+)-urbiprofen (0.3, 3 and 9 mg kg 71 ) which dose-relatedly reduced the number of c-Fos-LI neurons (r=0.69, P50.01) and diameters of paw and ankle (r=0.56 and r=0.52 respectively, P50.05 for both). 5 For the dose of 0.3 mg kg 71 i.v., R(7)-¯urbiprofen did not modify the number of c-Fos-LI neurons and produced a weak reduction of oedema at only the ankle level (23+12% reduction, P50.05). However, a ten times higher dose of R(7)-¯urbiprofen (3 mg kg 71 i.v.) was necessary to obtain e ects comparable to those of S(+)-or racemic-¯urbiprofen (0.3 mg kg 71 i.v.). 6 Intraplantar racemic-¯urbiprofen (1, 10 and 30 mg) dose-relatedly reduced the carrageenan-enhanced ankle diameter (r=0.81, P50.001) and the number of c-Fos-LI neurons in L4 ± L5 segments (r=0.83, P50.001), with a 60+3% reduction of the number of c-Fos-LI neurons (P50.001), and 30+3 and 67+7% reduction of paw and ankle diameter respectively (P50.001 for both) for the dose of 30 mg. 7 For intraplantar S(+)-¯urbiprofen (1, 10 and 30 mg) the dose-related e ects (r=0.77, r=0.60 and r=0.59 for c-Fos-LI neurons, paw and ankle diameters respectively, P50.001, P50.01 and P50.01) were similar to those of racemic-¯urbiprofen. In contrast, intraplantar R(7)-¯urbiprofen (1, 10 and 30 mg) did not have detectable e ects on all studied parameters. 8 The present study provides clear evidence for potent anti-in¯ammatory and antinociceptive e ects of both intravenous or intraplantar racemic-and S(+)-¯urbiprofen. These results further demonstrate marked anti-in¯ammatory and antinociceptive e ects of intravenous, but not intraplantar, R(7)-urbiprofen. These results suggest that the main site of action of racemic-and S(+)-¯urbiprofen is in the periphery and indicate that the site of action of R(7)-¯urbiprofen is mainly of central origin. Keywords: Carrageenan in¯ammation; c-Fos; dorsal horn; racemic-¯urbiprofen; S(+)-¯urbiprofen; R(7)-¯urbiprofen; nociception; NSAIDs; rat IntroductionFlurbiprofen is a member of the 2-arylpropionic acid (2-APA) class, also known as profens, an important group of nonsteroidal anti-in¯ammatory drugs (NSAIDs); f...

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Section: Resultssupporting

confidence: 73%

Section: Discussionsupporting

confidence: 78%

supporting

confidence: 74%

Section: Introductionmentioning

confidence: 99%

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Peripheral and/or central effects of racemic‐, S(+)‐ and R(−)‐flurbiprofen on inflammatory nociceptive processes: a c‐Fos protein study in the rat spinal cord

Buritova

Besson

1998

British J Pharmacology

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“…The aim of our study was to evaluate simultaneously the effects of the well established NOS inhibitor, L-NAME, on the peripheral signs of inflammation induced by carrageenin and the subsequent spinal expression of c-Fos (Draisci & Iadarola 1989;Noguchi et al, 1991;1992;Honore et al, 1994a). Intraplantar carrageenin (Winter et al, 1962) produces a classical inflammation (see references in Kocher et al, 1987) and a heat and mechanical hyperalgesia (Joris et al, 1990; see references in Ferreira et al, 1993).…”

Section: Introductionmentioning

confidence: 99%

Reduction of carrageenin oedema and the associated c‐Fos expression in the rat lumbar spinal cord by nitric oxide synthase inhibitor

Honoré

Chapman

Buritova

et al. 1995

British J Pharmacology

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1 Three hours after intraplantar carrageenin (6 mg/150flI of saline) Fos-like immunoreactivity (Fos-LI) was mainly observed in L4 and L5 segments of the dorsal horn. Both superficial (I-II) and deep laminae (V-VI) neurones were labelled. 2 We have studied the effect of systemic administration of a nitric oxide synthase inhibitor, N0-nitro-L-arginine methyl ester (L-NAME) on carrageenin evoked c-Fos expression and thus the contribution of nitric oxide to this expression.3 Pre-administration of L-NAME (10, 25, 50, 100 mg kg-', i.v.) dose-dependently reduced the number of superficial and deep laminae Fos-LI neurones, 100 mg kg-' produced a 63 ± 2% and 72±4% reduction of Fos-LI neurones respectively, P<0.0001 for both superficial and deep neurones. 4 Pre-administered L-NAME dose-relatedly reduced the carrageenin-evoked paw and ankle oedema, with 100 mg kg-' of L-NAME resulting in a 74 ± 2% and 103 ± 2% reduction respectively.5 Post-administration of L-NAME (10mgkg'1, i.v.) reduced the number of superficial and deep laminae Fos-LI neurones (65 ± 7% and 53 ± 8% reduction respectively, P<0.01 for both superficial and deep neurones). 6 Post-administered L-NAME reduced both the paw and ankle oedema (52 ± 8% and 62 ± 10% reduction respectively, P<0.0001 for both paw and ankle).7 Pre-administered D-NAME (100 mg kg-', i.v.), the inactive isomer of L-NAME, produced a weak reduction of the number of superficial laminae Fos-LI neurones (26 ± 8% reduction, P<0.05), without influencing the deep Fos-LI neurones (5 ± 8% enhancement) or the oedema.8 Systemic L-arginine (1200 mg kg') did not reverse the reduction of the total number of Fos-LI neurones induced by 100mg kg-' of L-NAME, or the effect of L-NAME on the paw and ankle oedema.9 Intraplantar L-arginine (30 mg) did not reverse the effect of L-NAME (100 mg kg') on the total number of Fos-LI neurones. However, the inhibitory effects of L-NAME on the paw and ankle oedema were partially reversed by intraplantar L-Arginine (34 ± 9% and 45 ± 11% reduction of carrageenin oedema respectively) with these effects being significant as compared to the effect of L-NAME alone (P<0.05 for both). 10 There is a strong correlation between the reduction of the number of Fos-LI neurones and the oedema by L-NAME, clearly demonstrating a predominant role of peripheral NO in the development of one of the signs of carrageenin inflammation.

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Alteredc-fos expression in the parabrachial nucleus in a rodent model of CFA-induced peripheral inflammation

Bellavance

Beitz

1996

J. Comp. Neurol.

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Increases in the expression of immediate early genes have been shown to occur in the lumbar spinal cord dorsal horn after peripheral inflammation. Given that the pontine parabrachial nucleus has been implicated in nociceptive as well as antinociceptive processes and is reciprocally connected with the spinal cord dorsal horn, it seems likely that peripheral inflammation will cause alterations in immediate early gene expression in this nucleus. To test this hypothesis we examined cFos-like immunoreactivity in a rodent complete Freund's adjuvant-induced peripheral inflammatory model of persistent nociception. Unilateral hind paw injections of complete Freund's adjuvant produced inflammation, hyperalgesia of the affected limb, and alterations in open field behaviors. Immunocytochemical analysis demonstrated a bilateral increase in cFos-like immunoreactivity in the lateral and Kolliker-Fuse subdivisions of the parabrachial nucleus at 6 and 24 hours postinjection and an ipsilateral decrease below basal levels in the Kolliker-Fuse subdivision at 96 hours postinjection when compared to saline controls. Taken together, these results suggest that select parabrachial neurons are activated by noxious somatic inflammation. These active parabrachial neurons are likely to participate in ascending nociceptive and/or descending antinociceptive pathways.

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Dynorphin expression and Fos-like immunoreactivity following inflammation induced hyperalgesia are colocalized in spinal cord neurons

Cited by 215 publications

References 28 publications

Peripheral and/or central effects of racemic‐, S(+)‐ and R(−)‐flurbiprofen on inflammatory nociceptive processes: a c‐Fos protein study in the rat spinal cord

Peripheral and/or central effects of racemic‐, S(+)‐ and R(−)‐flurbiprofen on inflammatory nociceptive processes: a c‐Fos protein study in the rat spinal cord

Reduction of carrageenin oedema and the associated c‐Fos expression in the rat lumbar spinal cord by nitric oxide synthase inhibitor

Alteredc-fos expression in the parabrachial nucleus in a rodent model of CFA-induced peripheral inflammation

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